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Protective effects of asperuloside against cyclophosphamide-induced urotoxicity and hematotoxicity in rats

  • Xiaozhuang Peng , Xiaomin Zhang , Chen Wang EMAIL logo and Opeyemi Joshua Olatunji EMAIL logo
Published/Copyright: December 3, 2022
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Open Chemistry
From the journal Open Chemistry Volume 20 Issue 1

Abstract

Cyclophosphamide (CP) is a highly efficacious chemotherapy drug for treating cancers and autoimmune disorders, but it is also notable for its deleterious side effects including urotoxicity in cancer patients, which has been extensively linked to CP-induced oxidative/inflammatory cascades. Herein, we investigated the protective effects of asperuloside (ASP) against CP-induced urotoxicity. Rats received oral administration of ASP (20 and 40 mg/kg bw/day) for 35 days and were injected with weekly CP (100 mg/kg bw, i.p.) for 4 weeks to induce acute bladder toxicity. CP acutely altered haematological parameters and significantly reduced body weight gain, bladder glutathione peroxidase, reduced glutathione, catalase, and superoxide dismutase activities. Furthermore, CP caused an upward surge in bladder malondialdehyde, nuclear factor-kappa B, tumour necrosis factor-α, interleukin-1β, and interleukin 6 concentrations. ASP supplementation ameliorated CP-induced haematological derangement and bladder urotoxicity through the restoration of oxidative and inflammatory parameters in CP-treated rats. These findings suggested that ASP could be valorised as a possible therapeutic agent against chemotherapy-related toxicities as well as oxidative damage disorders.

Keywords: asperuloside; cyclophosphamide; polyphenols; oxidative stress; inflammation; urotoxicity

1 Introduction

The rapid rise in the occurrence of immune-related disorders, cancers, and tumours has necessitated the development of relevant drugs that can entirely eliminate or mitigate the severity of these diseases. The advancement in pharmaceutical and medical sciences has led to the development of anticancer and immunosuppressive agents such as cyclophosphamide (CP). CP is an alkylating agent with extensive applications in the treatment of solid tumours, cancers (lymphoma, leukaemia, and multiple myeloma), and rheumatic arthritis [1,2]. Unfortunately, the protracted use of CP is characterised by several unpleasantries including immunosuppression, hair loss, bleeding, reproductive toxicity, bladder toxicity, and haemorrhagic cystitis, due to the formation of xenobiotic metabolites (acrolein) via enzymatic metabolism of CP [2,3,4,5]. CP-induced urotoxicity is associated with the accumulation of acrolein, which subsequently results in inflammation of the bladder, haematuria, dysuria, and haemorrhagic cystitis [5]. Mechanistically, acrolein, a very reactive metabolite generated from cytochromes P450 enzymatic metabolism of CP, is thought to provoke the generation of reactive oxygen species (ROS), leading to oxidative stress and impairment of the bladder antioxidant mechanism [3,6,7]. Furthermore, acrolein toxicity also destroys the lumen membrane, penetrating the uroepithelium leading to further accrual in ROS production in the bladder resulting in transepithelial permeability and inflammation [8,9]. Although ROS-induced oxidative damage has been identified as the major culprit responsible for CP-induced bladder toxicity, there are still no effective therapies in clinical practise to mitigate this toxicity [5]. Therefore, potential therapeutic approaches that are aimed at combating the major culprit implicated in CP-induced toxicity would have immense relevance in clinical application. Numerous studies have highlighted the potential of antioxidants as protective agents against CP-induced urotoxicity [3,10,11].

Lately, plant-derived constituents have been proposed as viable sources of protective agents against drugs/toxin-induced toxicities [12,13,14]. This has been largely attributed to their multi-component nature, thus affording the possibility of a multitargeted approach which is crucial for these ailments given their complex pathophysiology.

Asperuloside (ASP) is an iridoid glycoside that has been reported from several plants in the family Rubiaceae family including Asperula odorata, Paederia foetida, and Goldhair Hedyotis. The pharmacological potency of ASP has been previously reported especially its antitumour, anti-inflammatory, antioxidant, and antibacterial activities [15,16,17]. The protective effects of ASP against LPS-induced acute lung injury and DSS-induced chronic colitis through its modulatory effects of oxidative stress and inflammation have been reported [15,18]. However, despite the avalanche of reports regarding the biological effects of ASP, there is currently no information on the potential role of the modulation of CP-induced urotoxicity. Considering the potential benefits of ASP outlined earlier, we envisaged that ASP could afford protection against CP-induced urotoxicity. Accordingly, this work focused on evaluating the uroprotective effects of ASP in CP models of bladder toxicity.

2 Materials and methods

2.1 Biological sample

ASP (purchased from Shanghai Yuanye Biotechnology Co., Ltd. Shanghai, China) was provided by Prof Jian Tang (Bozhou University). CP was purchased from Alfa Aesar (Massachusetts, USA). All other chemicals used were of analytical grade.

2.2 Animals

Seven-week-old male rats of the Wistar albino lineage were used in this study. The animals were accommodated at 23 ± 2°C and a light/dark cycle of 12 h with water and food ad libitum. The animals were habituated to the conditions in the animal house facility for one week. Ethical guidelines of the National Institute of Health (Revised edition of 1978) were strictly followed during the experimental procedures. In addition, ethical approval was secured from the Committee on Animal Ethics of Shanghai Pudong New Area Peoples Hospital (2020/011/20).

2.3 Experimental design

The rats were arbitrarily assigned into four groups (n = 6 in each group). The rats in groups I and II were designated as normal control and CP control, respectively, and they were treated with normal saline for 35 consecutive days. Groups III and IV rats were given ASP orally at concentrations of 20 and 40 mg/kg bw, respectively, for 35 consecutive days. After the first week of treatment, the rats in groups II–IV were injected with 100 mg/kg bw of CP weekly (once a week) from the 2nd to 5th weeks. ASP and CP were dissolved in normal saline prior to administration to the rats. The doses of ASP and CP were based on our earlier studies [18,19]. Following the last treatment of ASP, the rats were sacrificed under sodium thiopental anaesthesia (150 mg/kg, i.p.), and peripheral blood samples were collected through the cardiac puncture into EDTA bottles. The collected blood was used to determine haematological parameters. On the other hand, the bladder from each of the animals was dissected out, cleaned, subsequently homogenised in PBS (0.1 M, pH 7.4; 1:9 w/v) and centrifuged at 6,000 g for 20 min at 4°C to afford supernatants that were used for subsequent biochemical assays.

2.4 Estimation of oxidative stress markers in the bladder

The activities of catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels in the supernatant homogenates obtained from the bladder were determined with biochemical kits (Nanjing Jiancheng Bioengineering Institute, China).

2.5 Estimation of cytokines and NF-κB in the bladder

The concentrations of cytokines tumour necrosis factor-α (TNF-α), interleukins-1β and 6 (IL-1β and IL-6), and nuclear factor kappa B were determined in the homogenate supernatant obtained from the bladder using ELISA kits (Abcam, Cambridge, United Kingdom)

2.6 Statistical data analysis

All findings were presented as mean ± SD. Results were analysed for statistical significance using one-way ANOVA and Tukey multiple comparisons test using Graph Pad Prism software (version 5). Results were considered statistically significant at p < 0.05.

3 Results

3.1 Effect of ASP and CP on body weight gain of rats

Table 1 shows the effect of ASP on the body weight gain of the animals. There was an obvious and significant reduction in the body weight of the animals in the CP group from the third to the fifth of CP injection compared to the normal control, whereas the rats in the ASP-treated groups showed significant body weight gain when compared with the CP group during the same period (Table 1).

Table 1

Effect of ASP on body weight in CP-treated rats

Body weight (g) Treatment groups
Normal control CP control ASP20 + CP ASP40 + CP
Week 1 245.8 ± 10.68 251.6 ± 5.16 263.3 ± 16.93 266.6 ± 20.16
Week 2 287.5 ± 19.70 303.3 ± 5.16 297.5 ± 10.83 304.1 ± 13.93
Week 3 333.3 ± 20.89 289.1 ± 11.58b 295.8 ± 18.28 318.3 ± 23.38
Week 4 370.8 ± 15.62 270.0 ± 13.03a 315.0 ± 13.41c 343.3 ± 21.83c
Week 5 418.3 ± 15.70 256.7 ± 16.32a 329.1 ± 19.34c 370.8 ± 40.19c

Data were analysed using one-way ANOVA and Tukey’s post hoc test (GraphPad Prism); a: significantly different from the control group at p < 0.001; b: significantly different from the control group at p < 0.05; c: significantly different from CP group at p < 0.001.

3.2 ASP improved CP-induced haematological alterations

As portrayed in Table 2, the haematological parameters including RBC count, Hb, and Hct were markedly lowered in response to CP treatment as compared to the normal control group. Conversely, treatment with ASP significantly increased these parameters compared with CP control rats. Meanwhile, the results shown in Table 2 also indicated that CP markedly reduced lymphocyte and monocyte counts, while neutrophil was significantly increased when juxtaposed with the corresponding values from the normal control group. Nevertheless, the administration of ASP improved these white blood cell parameters in comparison with the CP control group (Table 2).

Table 2

Effect of ASP on haematological parameters in CP-treated rats

Parameters Treatment groups
Normal control CP control ASP20 + CP ASP40 + CP
RBC (× 106/mm3) 8.53 ± 0.62 1.69 ± 0.83a 8.194 ± 1.40b 9.20 ± 0.36b
Hb (g/dL) 16.08 ± 0.60 5.46 ± 2.32a 14.76 ± 2.43b 16.81 ± 0.63b
Hct (g/dL) 49.05 ± 0.35 23.70 ± 3.66a 43.22 ± 8.12b 50.61 ± 0.59b
MCV (fL) 53.66 ± 2.33 55.16 ± 3.31 52.60 ± 1.14 54.83 ± 2.48
MCH (pg) 17.58 ± 0.45 19.08 ± 0.71 18.06 ± 0.45 18.33 ± 0.26
MCHC (g/dL) 33.08 ± 1.10 34.23 ± 3.04 34.32 ± 1.15 33.43 ± 1.06
WBC (× 103/mm3) 7.28 ± 0.89 2.20 ± 0.48a 6.96 ± 1.75b 7.72 ± 3.43b
Neutrophils (%) 8.33 ± 1.23 45.50 ± 10.21a 21.80 ± 10.35b 15.75 ± 2.62b
Lymphocytes (%) 42.28 ± 8.67 18.66 ± 2.50a 35.60 ± 9.68b 40.00 ± 9.73b
Monocytes (%) 8.66 ± 0.81 4.00 ± 1.41a 7.40 ± 2.30c 8.83 ± 1.32b

Data were analysed using one-way ANOVA and Tukey’s post hoc test (GraphPad Prism); a: significantly different from the control group at p < 0.001; b: significantly different from CP group at p < 0.001; c: significantly different from CP group at p < 0.01.

3.3 ASP deterred oxidative stress and upregulated antioxidant enzymes

The findings shown in Table 3 revealed that the bladder levels of SOD, CAT, GSH, and GPx were notably depressed, while MDA levels were significantly higher in response to CP toxicity when compared with corresponding values from the normal control group. As envisaged, supplementation with ASP suppressed oxidative stress as evidenced by increased bladder antioxidant enzyme activities in comparison with the CP control group, while simultaneously decreasing MDA levels relative to the CP control group.

Table 3

Effect of ASP on bladder oxidative stress and antioxidant in CP-treated rats

Parameters Treatment groups
Normal control CP control ASP20 + CP ASP40 + CP
SOD (U/mg prot) 11.83 ± 2.68 4.54 ± 0.61a 7.55 ± 0.69c,d 9.47 ± 1.18b
GSH (µmol/g tissue) 9.33 ± 0.56 3.50 ± 0.55a 6.62 ± 0.49b,d 7.77 ± 0.55b
GPx (U/mg prot) 26.57 ± 2.87 12.02 ± 2.05a 16.85 ± 1.27c 20.28 ± 1.98b
CAT (U/mg prot) 62.65 ± 3.02 31.46 ± 5.66a 42.34 ± 4.35c,d 50.29 ± 3.83b
MDA (nmol/mg prot) 1.22 ± 0.13 3.70 ± 0.35a 2.13 ± 0.10b 1.89 ± 1.17b

Data were analysed using one-way ANOVA and Tukey’s post hoc test (GraphPad Prism); a: significantly different from the control group at p < 0.001; b: significantly different from the CP group at p < 0.001; c: significantly different from CP group at p < 0.01; c: significantly different from CP group at p < 0.05; d: significantly different from ASP40 + CP group at p < 0.05.

3.4 ASP supplementation suppressed cytokines and NF-κB levels

Figure 1a–d shows the bladder proinflammatory cytokines and NF-κB status. Treatment with CP was associated with notable increases in the bladder cytokine concentrations including TNF-α, IL-6, and IL-1β compared with the normal control group. Contrarily, an obvious reduction in these cytokines levels was observed in the ASP-treated groups in comparison with the CP group (Figure 1a–c). Additionally, CP induced a marked increase in NF-κB levels compared to the normal control group, while supplementation with ASP considerably decreased NF-κB levels when juxtaposed to the CP control group (Figure 1d).

Figure 1 Effect of ASP on proinflammatory mediators in the bladder homogenates of CP treated rats. Data were analysed by one-way ANOVA followed by Tukey post hoc test using GraphPad Prism. (a) significantly different from control group at P < 0.001; (b) significantly different from CP group at P < 0.001; (c) significantly different from CP group at P < 0.01; (d) significantly different from CP group at P < 0.05; (e) significantly different from ASP40 + CP group at P < 0.05.
Figure 1

Effect of ASP on proinflammatory mediators in the bladder homogenates of CP treated rats. Data were analysed by one-way ANOVA followed by Tukey post hoc test using GraphPad Prism. (a) significantly different from control group at P < 0.001; (b) significantly different from CP group at P < 0.001; (c) significantly different from CP group at P < 0.01; (d) significantly different from CP group at P < 0.05; (e) significantly different from ASP40 + CP group at P < 0.05.

4 Discussion

The advancement in medical sciences has been validated by the emergence of several potent drugs for the treatment of various devastating diseases, including cancer which has substantially improved the quality of patients' life. However, most of these drugs are not free of unwanted side effects which may be life-threatening in some cases. Specifically, the anticancer drug CP exerts its anticancer effects on target cells by breaking DNA strands and suppressing cell proliferation leading to mitochondria apoptotic cell death [20,21]. However, this effect is not only limited to cancer cells, normal healthy cells are also affected, leading to various CP-induced organ toxicities [22]. CP-induced urotoxicity is a prevalent side effect associated with prolonged treatment, which cannot be overlooked due to the risk of kidney failure or even death. Haemorrhagic cystitis is the clinical manifestation of CP-induced bladder toxicity, and there are no effective therapy in place to mitigate this complication [3]. This has necessitated the search for alternative therapies with the ability to counteract CP toxicity in the bladder. This study was therefore undertaken to investigate the uroprotective potentials of ASP on CP-induced bladder toxicity.

The study results obtained evidently attests effect of ASP on CP-induced oxidative damage on the bladder. In agreement with other previous researchers, the observations from this study indicated that CP treatment induced urotoxicity which was associated with significant bladder oxidative stress and inflammation [4,5,10]. Undoubtedly, the generation of ROS has been principally implicated in the trajectory of CP bladder toxicity, owing to the enzymatic metabolism of CP to cytotoxic metabolites including acrolein and phosphoramide mustard [23,24]. Acrolein, an extremely reactive toxic CP metabolite, is the major culprit that instigates oxidative damage in the urinary bladder [11,23]. Numerous studies have illustrated that agents that can deter or scavenge ROS generation as well as preserve antioxidant mercenaries show potent potential for ameliorating CP-induced toxicities [25]. The results from this study strongly implicated CP in bladder oxidative stress as evidenced by considerable curtailment in CAT, SOD, GSH, and GPx activities, whilst MDA concentration was grossly elevated. In contrast, treatment with ASP restored the altered antioxidant defense types of machinery and depleted lipid peroxidation markers.

Compelling evidence have highlighted the cordial relationship between altered redox homeostasis and inflammatory cascades. Several studies have indicated that oxidative stress and excessive generation of ROS can initiate a series of inflammatory reactions in a wide range of diseases including CP-induced urotoxicity [23,26]. The results from this study suggested that CP induced a significant inflammatory reaction in the bladder of the treated rats as illustrated by increased concentrations of NF-κB. Bladder inflammation plays a major role in the pathogenesis of haemorrhagic cystitis [3,26]. The vulnerability of the bladder to acrolein toxicity enhances the activation of NF-kB, a relatively sensitive ROS/oxidative stress transcriptional factor. The activation of NF-kB compels the release of proinflammatory mediators like TNF-α, IL-6, and IL-1β, in addition to further ROS generation. This process leads to vascular dilatation, mucosal oedema, and capillary fragility leading to haemorrhage and necrosis [27]. In the sequel, we observed that the levels of IL-1β, TNF-α, and IL-6 in the bladder were appreciably increased in the rats exposed to CP treatment, suggesting inflammation of the bladder, which was in unison with other earlier studies [4,5,28,29]. Treatment with ASP exerted a pronounced anti-inflammatory effects as indicated by decrease in these mediators of inflammation (IL-1β, IL-6, TNF-α, and NF-κB).

The results from the current study revealed that treatment with CP caused stupendous alterations in haematological parameters and pancytopenia as indicated by a marked decrease in the RBC, WBC, Hb, and Hct levels, suggesting immune suppression. CP obtrudes the processes involved in the synthesis of DNA as well as proliferation of normal tissues such as progenitor stem cells in the bone marrow, resulting in pancytopenia [30,31]. Additionally, CP-induced myelosuppression is also thought to be mediated through its reductive capacity on the synthesis of erythropoietin as well as hematopoietic alterations [31]. The results from this study corroborated with what was previously described by Elshater et al. [32]. CP toxicity significantly reduced the red blood cell count, haemoglobin, haematocrit, lymphocyte, and monocyte counts, while neutrophil markedly increased the suggestion of myelosuppression. Nevertheless, the administration of ASP improved these white blood cell parameters in comparison with the CP control group. Our findings portrayed that treatment with ASP significantly alleviated CP-induced alterations of these haematological parameters.

The protective effects of ASP on CP toxicity may be associated with its strong antioxidant and anti-inflammatory properties since the pathogenesis of CP is strongly related to oxidative stress. In a previous study, Chen et al. revealed that ASP attenuated weight loss, reduced colon inflammatory mediators, restored antioxidant capacity, and modulated oxidative stress by upregulating Nrf2, HO-1, and NQO-1 proteins expressions in DSS-induced chronic colitis animals [15]. In addition, ASP was reported to markedly reduce proinflammatory (TNF-α, IL-1β, and IL-6 levels), myeloperoxidase activity, the phosphorylation IκBα, ERK1/2, JNK, and p38MAPK in LPS-induced acute lung injury [18]. All these previous studies corroborated the results obtained in this present study. This study is the first report on the protective effects of ASP against CP-induced bladder toxicity. With the increase in the oxidative damage-related devastating side effects associated with the use of chemotherapy, the rich bioactive depiction of ASP thus presents a potential pharmacotherapeutic alternative source.

Based on the findings presented in this study, it is imperative to conclude that CP-induced urotoxicity was associated with oxidative stress and inflammation and ASP showed uroprotective effects which were mediated through its antioxidant and anti-inflammatory activities. Further investigations on the mechanism of protection are required.

Acknowledgment

None.

  1. Funding information: Not applicable.

  2. Author contributions: Conceptualisation – Opeyemi Joshua Olatunji; methodology – Xiaozhuang Peng and Xiaomin Zhang; formal analysis – Xiaozhuang Peng, Xiaomin Zhang, and Chen Wang; investigation – Xiaozhuang Peng, Xiaomin Zhang, Chen Wang, and Opeyemi Joshua Olatunji; writing and original draft preparation – Xiaozhuang Peng and Opeyemi Joshua Olatunji; project administration – Chen Wang and Opeyemi Joshua Olatunji; funding acquisition – Xiaozhuang Peng. All the authors approved the final manuscript version submitted.

  3. Conflict of interest: The authors declare no conflicts of interest regarding this article.

  4. Informed consent: Not applicable.

  5. Ethical approval: Ethical approval was secured from the Committee on Animal Ethics of Shanghai Pudong New Area Peoples Hospital (2020/011/20).

  6. Data availability statement: The data sets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Received: 2022-08-02
Revised: 2022-09-28
Accepted: 2022-10-22
Published Online: 2022-12-03

© 2022 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  12. Petrology and geochemistry of multiphase post-granitic dikes: A case study from the Gabal Serbal area, Southwestern Sinai, Egypt
  13. Comparison of the yield and purity of plasma exosomes extracted by ultracentrifugation, precipitation, and membrane-based approaches
  14. Bioactive triterpenoids from Indonesian medicinal plant Syzygium aqueum
  15. Investigation of the effects of machining parameters on surface integrity in micromachining
  16. The mesoporous aluminosilicate application as support for bifunctional catalysts for n-hexadecane hydroconversion
  17. Gamma-ray shielding properties of Nd2O3-added iron–boron–phosphate-based composites
  18. Numerical investigation on perforated sheet metals under tension loading
  19. Statistical analysis on the radiological assessment and geochemical studies of granite rocks in the north of Um Taghir area, Eastern Desert, Egypt
  20. Two new polypodane-type bicyclic triterpenoids from mastic
  21. Structural, physical, and mechanical properties of the TiO2 added hydroxyapatite composites
  22. Tribological properties and characterization of borided Co–Mg alloys
  23. Studies on Anemone nemorosa L. extracts; polyphenols profile, antioxidant activity, and effects on Caco-2 cells by in vitro and in silico studies
  24. Mechanical properties, elastic moduli, transmission factors, and gamma-ray-shielding performances of Bi2O3–P2O5–B2O3–V2O5 quaternary glass system
  25. Cyclic connectivity index of bipolar fuzzy incidence graph
  26. The role of passage numbers of donor cells in the development of Arabian Oryx – Cow interspecific somatic cell nuclear transfer embryos
  27. Mechanical property evaluation of tellurite–germanate glasses and comparison of their radiation-shielding characteristics using EPICS2017 to other glass systems
  28. Molecular screening of ionic liquids for CO2 absorption and molecular dynamic simulation
  29. Microwave-assisted preparation of Ag/Fe magnetic biochar from clivia leaves for adsorbing daptomycin antibiotics
  30. Iminodisuccinic acid enhances antioxidant and mineral element accumulation in young leaves of Ziziphus jujuba
  31. Cytotoxic activity of guaiane-type sesquiterpene lactone (deoxycynaropicrin) isolated from the leaves of Centaurothamnus maximus
  32. Effects of welding parameters on the angular distortion of welded steel plates
  33. Simulation of a reactor considering the Stamicarbon, Snamprogetti, and Toyo patents for obtaining urea
  34. Effect of different ramie (Boehmeria nivea L. Gaud) cultivars on the adsorption of heavy metal ions cadmium and lead in the remediation of contaminated farmland soils
  35. Impact of a live bacterial-based direct-fed microbial (DFM) postpartum and weaning system on performance, mortality, and health of Najdi lambs
  36. Anti-tumor effect of liposomes containing extracted Murrayafoline A against liver cancer cells in 2D and 3D cultured models
  37. Physicochemical properties and some mineral concentration of milk samples from different animals and altitudes
  38. Copper(ii) complexes supported by modified azo-based ligands: Nucleic acid binding and molecular docking studies
  39. Diagnostic and therapeutic radioisotopes in nuclear medicine: Determination of gamma-ray transmission factors and safety competencies of high-dense and transparent glassy shields
  40. Calculation of NaI(Tl) detector efficiency using 226Ra, 232Th, and 40K radioisotopes: Three-phase Monte Carlo simulation study
  41. Isolation and identification of unstable components from Caesalpinia sappan by high-speed counter-current chromatography combined with preparative high-performance liquid chromatography
  42. Quantification of biomarkers and evaluation of antioxidant, anti-inflammatory, and cytotoxicity properties of Dodonaea viscosa grown in Saudi Arabia using HPTLC technique
  43. Characterization of the elastic modulus of ceramic–metal composites with physical and mechanical properties by ultrasonic technique
  44. GC-MS analysis of Vespa velutina auraria Smith and its anti-inflammatory and antioxidant activities in vitro
  45. Texturing of nanocoatings for surface acoustic wave-based sensors for volatile organic compounds
  46. Insights into the molecular basis of some chalcone analogues as potential inhibitors of Leishmania donovani: An integrated in silico and in vitro study
  47. (1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexyl 4-amino-3-phenylbutanoate hydrochloride: Synthesis and anticonvulsant activity
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  50. Rapeseed oil-based hippurate amide nanocomposite coating material for anticorrosive and antibacterial applications
  51. Chemically modified Teucrium polium (Lamiaceae) plant act as an effective adsorbent tool for potassium permanganate (KMnO4) in wastewater remediation
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  55. Mechanical and gamma-ray shielding examinations of Bi2O3–PbO–CdO–B2O3 glass system
  56. Machine learning-based forecasting of potability of drinking water through adaptive boosting model
  57. The potential effect of the Rumex vesicarius water seeds extract treatment on mice before and during pregnancy on the serum enzymes and the histology of kidney and liver
  58. Impact of benzimidazole functional groups on the n-doping properties of benzimidazole derivatives
  59. Extraction of red pigment from Chinese jujube peel and the antioxidant activity of the pigment extracts
  60. Flexural strength and thermal properties of carbon black nanoparticle reinforced epoxy composites obtained from waste tires
  61. A focusing study on radioprotective and antioxidant effects of Annona muricata leaf extract in the circulation and liver tissue: Clinical and experimental studies
  62. Clinical comprehensive and experimental assessment of the radioprotective effect of Annona muricata leaf extract to prevent cellular damage in the ileum tissue
  63. Effect of WC content on ultrasonic properties, thermal and electrical conductivity of WC–Co–Ni–Cr composites
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  65. The synthesis of nanocellulose-based nanocomposites for the effective removal of hexavalent chromium ions from aqueous solution
  66. Study on the influence of physical interlayers on the remaining oil production under different development modes
  67. Optimized linear regression control of DC motor under various disturbances
  68. Influence of different sample preparation strategies on hypothesis-driven shotgun proteomic analysis of human saliva
  69. Determination of flow distance of the fluid metal due to fluidity in ductile iron casting by artificial neural networks approach
  70. Investigation of mechanical activation effect on high-volume natural pozzolanic cements
  71. In vitro: Anti-coccidia activity of Calotropis procera leaf extract on Eimeria papillata oocysts sporulation and sporozoite
  72. Determination of oil composition of cowpea (Vigna unguiculata L.) seeds under influence of organic fertilizer forms
  73. Activated partial thromboplastin time maybe associated with the prognosis of papillary thyroid carcinoma
  74. Treatment of rat brain ischemia model by NSCs-polymer scaffold transplantation
  75. Lead and cadmium removal with native yeast from coastal wetlands
  76. Characterization of electroless Ni-coated Fe–Co composite using powder metallurgy
  77. Ferrate synthesis using NaOCl and its application for dye removal
  78. Antioxidant, antidiabetic, and anticholinesterase potential of Chenopodium murale L. extracts using in vitro and in vivo approaches
  79. Study on essential oil, antioxidant activity, anti-human prostate cancer effects, and induction of apoptosis by Equisetum arvense
  80. Experimental study on turning machine with permanent magnetic cutting tool
  81. Numerical simulation and mathematical modeling of the casting process for pearlitic spheroidal graphite cast iron
  82. Design, synthesis, and cytotoxicity evaluation of novel thiophene, pyrimidine, pyridazine, and pyridine: Griseofulvin heterocyclic extension derivatives
  83. Isolation and identification of promising antibiotic-producing bacteria
  84. Ultrasonic-induced reversible blood–brain barrier opening: Safety evaluation into the cellular level
  85. Evaluation of phytochemical and antioxidant potential of various extracts from traditionally used medicinal plants of Pakistan
  86. Effect of calcium lactate in standard diet on selected markers of oxidative stress and inflammation in ovariectomized rats
  87. Identification of crucial salivary proteins/genes and pathways involved in pathogenesis of temporomandibular disorders
  88. Zirconium-modified attapulgite was used for removing of Cr(vi) in aqueous solution
  89. The stress distribution of different types of restorative materials in primary molar
  90. Reducing surface heat loss in steam boilers
  91. Deformation behavior and formability of friction stir processed DP600 steel
  92. Synthesis and characterization of bismuth oxide/commercial activated carbon composite for battery anode
  93. Phytochemical analysis of Ziziphus jujube leaf at different foliar ages based on widely targeted metabolomics
  94. Effects of in ovo injection of black cumin (Nigella sativa) extract on hatching performance of broiler eggs
  95. Separation and evaluation of potential antioxidant, analgesic, and anti-inflammatory activities of limonene-rich essential oils from Citrus sinensis (L.)
  96. Bioactivity of a polyhydroxy gorgostane steroid from Xenia umbellata
  97. BiCAM-based automated scoring system for digital logic circuit diagrams
  98. Analysis of standard systems with solar monitoring systems
  99. Structural and spectroscopic properties of voriconazole and fluconazole – Experimental and theoretical studies
  100. New plant resistance inducers based on polyamines
  101. Experimental investigation of single-lap bolted and bolted/bonded (hybrid) joints of polymeric plates
  102. Investigation of inlet air pressure and evaporative cooling of four different cogeneration cycles
  103. Review Articles
  104. Comprehensive review on synthesis, physicochemical properties, and application of activated carbon from the Arecaceae plants for enhanced wastewater treatment
  105. Research progress on speciation analysis of arsenic in traditional Chinese medicine
  106. Recent modified air-assisted liquid–liquid microextraction applications for medicines and organic compounds in various samples: A review
  107. An insight on Vietnamese bio-waste materials as activated carbon precursors for multiple applications in environmental protection
  108. Antimicrobial activities of the extracts and secondary metabolites from Clausena genus – A review
  109. Bioremediation of organic/heavy metal contaminants by mixed cultures of microorganisms: A review
  110. Sonodynamic therapy for breast cancer: A literature review
  111. Recent progress of amino acid transporters as a novel antitumor target
  112. Aconitum coreanum Rapaics: Botany, traditional uses, phytochemistry, pharmacology, and toxicology
  113. Corrigendum
  114. Corrigendum to “Petrology and geochemistry of multiphase post-granitic dikes: A case study from the Gabal Serbal area, Southwestern Sinai, Egypt”
  115. Corrigendum to “Design of a Robust sliding mode controller for bioreactor cultures in overflow metabolism via an interdisciplinary approach”
  116. Corrigendum to “Statistical analysis on the radiological assessment and geochemical studies of granite rocks in the north of Um Taghir area, Eastern Desert, Egypt”
  117. Corrigendum to “Aroma components of tobacco powder from different producing areas based on gas chromatography ion mobility spectrometry”
  118. Corrigendum to “Mechanical properties, elastic moduli, transmission factors, and gamma-ray-shielding performances of Bi2O3–P2O5–B2O3–V2O5 quaternary glass system”
  119. Erratum
  120. Erratum to “Copper(ii) complexes supported by modified azo-based ligands: Nucleic acid binding and molecular docking studies”
  121. Special Issue on Applied Biochemistry and Biotechnology (ABB 2021)
  122. Study of solidification and stabilization of heavy metals by passivators in heavy metal-contaminated soil
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https://doi.org/10.1515/chem-2022-0234
Keywords for this article
asperuloside; cyclophosphamide; polyphenols; oxidative stress; inflammation; urotoxicity
Creative Commons
BY 4.0

Articles in the same Issue

  1. Regular Articles
  2. Photocatalytic degradation of Rhodamine B in aqueous phase by bimetallic metal-organic framework M/Fe-MOF (M = Co, Cu, and Mg)
  3. Assessment of using electronic portal imaging device for analysing bolus material utilised in radiation therapy
  4. A detailed investigation on highly dense CuZr bulk metallic glasses for shielding purposes
  5. Simulation of gamma-ray shielding properties for materials of medical interest
  6. Environmental impact assesment regulation applications and their analysis in Turkey
  7. Sample age effect on parameters of dynamic nuclear polarization in certain difluorobenzen isomers/MC800 asphaltene suspensions
  8. Passenger demand forecasting for railway systems
  9. Design of a Robust sliding mode controller for bioreactor cultures in overflow metabolism via an interdisciplinary approach
  10. Gamma, neutron, and heavy charged ion shielding properties of Er3+-doped and Sm3+-doped zinc borate glasses
  11. Bridging chiral de-tert-butylcalix[4]arenes: Optical resolution based on column chromatography and structural characterization
  12. Petrology and geochemistry of multiphase post-granitic dikes: A case study from the Gabal Serbal area, Southwestern Sinai, Egypt
  13. Comparison of the yield and purity of plasma exosomes extracted by ultracentrifugation, precipitation, and membrane-based approaches
  14. Bioactive triterpenoids from Indonesian medicinal plant Syzygium aqueum
  15. Investigation of the effects of machining parameters on surface integrity in micromachining
  16. The mesoporous aluminosilicate application as support for bifunctional catalysts for n-hexadecane hydroconversion
  17. Gamma-ray shielding properties of Nd2O3-added iron–boron–phosphate-based composites
  18. Numerical investigation on perforated sheet metals under tension loading
  19. Statistical analysis on the radiological assessment and geochemical studies of granite rocks in the north of Um Taghir area, Eastern Desert, Egypt
  20. Two new polypodane-type bicyclic triterpenoids from mastic
  21. Structural, physical, and mechanical properties of the TiO2 added hydroxyapatite composites
  22. Tribological properties and characterization of borided Co–Mg alloys
  23. Studies on Anemone nemorosa L. extracts; polyphenols profile, antioxidant activity, and effects on Caco-2 cells by in vitro and in silico studies
  24. Mechanical properties, elastic moduli, transmission factors, and gamma-ray-shielding performances of Bi2O3–P2O5–B2O3–V2O5 quaternary glass system
  25. Cyclic connectivity index of bipolar fuzzy incidence graph
  26. The role of passage numbers of donor cells in the development of Arabian Oryx – Cow interspecific somatic cell nuclear transfer embryos
  27. Mechanical property evaluation of tellurite–germanate glasses and comparison of their radiation-shielding characteristics using EPICS2017 to other glass systems
  28. Molecular screening of ionic liquids for CO2 absorption and molecular dynamic simulation
  29. Microwave-assisted preparation of Ag/Fe magnetic biochar from clivia leaves for adsorbing daptomycin antibiotics
  30. Iminodisuccinic acid enhances antioxidant and mineral element accumulation in young leaves of Ziziphus jujuba
  31. Cytotoxic activity of guaiane-type sesquiterpene lactone (deoxycynaropicrin) isolated from the leaves of Centaurothamnus maximus
  32. Effects of welding parameters on the angular distortion of welded steel plates
  33. Simulation of a reactor considering the Stamicarbon, Snamprogetti, and Toyo patents for obtaining urea
  34. Effect of different ramie (Boehmeria nivea L. Gaud) cultivars on the adsorption of heavy metal ions cadmium and lead in the remediation of contaminated farmland soils
  35. Impact of a live bacterial-based direct-fed microbial (DFM) postpartum and weaning system on performance, mortality, and health of Najdi lambs
  36. Anti-tumor effect of liposomes containing extracted Murrayafoline A against liver cancer cells in 2D and 3D cultured models
  37. Physicochemical properties and some mineral concentration of milk samples from different animals and altitudes
  38. Copper(ii) complexes supported by modified azo-based ligands: Nucleic acid binding and molecular docking studies
  39. Diagnostic and therapeutic radioisotopes in nuclear medicine: Determination of gamma-ray transmission factors and safety competencies of high-dense and transparent glassy shields
  40. Calculation of NaI(Tl) detector efficiency using 226Ra, 232Th, and 40K radioisotopes: Three-phase Monte Carlo simulation study
  41. Isolation and identification of unstable components from Caesalpinia sappan by high-speed counter-current chromatography combined with preparative high-performance liquid chromatography
  42. Quantification of biomarkers and evaluation of antioxidant, anti-inflammatory, and cytotoxicity properties of Dodonaea viscosa grown in Saudi Arabia using HPTLC technique
  43. Characterization of the elastic modulus of ceramic–metal composites with physical and mechanical properties by ultrasonic technique
  44. GC-MS analysis of Vespa velutina auraria Smith and its anti-inflammatory and antioxidant activities in vitro
  45. Texturing of nanocoatings for surface acoustic wave-based sensors for volatile organic compounds
  46. Insights into the molecular basis of some chalcone analogues as potential inhibitors of Leishmania donovani: An integrated in silico and in vitro study
  47. (1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexyl 4-amino-3-phenylbutanoate hydrochloride: Synthesis and anticonvulsant activity
  48. On the relative extraction rates of colour compounds and caffeine during brewing, an investigation of tea over time and temperature
  49. Characterization of egg shell powder-doped ceramic–metal composites
  50. Rapeseed oil-based hippurate amide nanocomposite coating material for anticorrosive and antibacterial applications
  51. Chemically modified Teucrium polium (Lamiaceae) plant act as an effective adsorbent tool for potassium permanganate (KMnO4) in wastewater remediation
  52. Efficiency analysis of photovoltaic systems installed in different geographical locations
  53. Risk prioritization model driven by success factor in the light of multicriteria decision making
  54. Theoretical investigations on the excited-state intramolecular proton transfer in the solvated 2-hydroxy-1-naphthaldehyde carbohydrazone
  55. Mechanical and gamma-ray shielding examinations of Bi2O3–PbO–CdO–B2O3 glass system
  56. Machine learning-based forecasting of potability of drinking water through adaptive boosting model
  57. The potential effect of the Rumex vesicarius water seeds extract treatment on mice before and during pregnancy on the serum enzymes and the histology of kidney and liver
  58. Impact of benzimidazole functional groups on the n-doping properties of benzimidazole derivatives
  59. Extraction of red pigment from Chinese jujube peel and the antioxidant activity of the pigment extracts
  60. Flexural strength and thermal properties of carbon black nanoparticle reinforced epoxy composites obtained from waste tires
  61. A focusing study on radioprotective and antioxidant effects of Annona muricata leaf extract in the circulation and liver tissue: Clinical and experimental studies
  62. Clinical comprehensive and experimental assessment of the radioprotective effect of Annona muricata leaf extract to prevent cellular damage in the ileum tissue
  63. Effect of WC content on ultrasonic properties, thermal and electrical conductivity of WC–Co–Ni–Cr composites
  64. Influence of various class cleaning agents for prosthesis on Co–Cr alloy surface
  65. The synthesis of nanocellulose-based nanocomposites for the effective removal of hexavalent chromium ions from aqueous solution
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  67. Optimized linear regression control of DC motor under various disturbances
  68. Influence of different sample preparation strategies on hypothesis-driven shotgun proteomic analysis of human saliva
  69. Determination of flow distance of the fluid metal due to fluidity in ductile iron casting by artificial neural networks approach
  70. Investigation of mechanical activation effect on high-volume natural pozzolanic cements
  71. In vitro: Anti-coccidia activity of Calotropis procera leaf extract on Eimeria papillata oocysts sporulation and sporozoite
  72. Determination of oil composition of cowpea (Vigna unguiculata L.) seeds under influence of organic fertilizer forms
  73. Activated partial thromboplastin time maybe associated with the prognosis of papillary thyroid carcinoma
  74. Treatment of rat brain ischemia model by NSCs-polymer scaffold transplantation
  75. Lead and cadmium removal with native yeast from coastal wetlands
  76. Characterization of electroless Ni-coated Fe–Co composite using powder metallurgy
  77. Ferrate synthesis using NaOCl and its application for dye removal
  78. Antioxidant, antidiabetic, and anticholinesterase potential of Chenopodium murale L. extracts using in vitro and in vivo approaches
  79. Study on essential oil, antioxidant activity, anti-human prostate cancer effects, and induction of apoptosis by Equisetum arvense
  80. Experimental study on turning machine with permanent magnetic cutting tool
  81. Numerical simulation and mathematical modeling of the casting process for pearlitic spheroidal graphite cast iron
  82. Design, synthesis, and cytotoxicity evaluation of novel thiophene, pyrimidine, pyridazine, and pyridine: Griseofulvin heterocyclic extension derivatives
  83. Isolation and identification of promising antibiotic-producing bacteria
  84. Ultrasonic-induced reversible blood–brain barrier opening: Safety evaluation into the cellular level
  85. Evaluation of phytochemical and antioxidant potential of various extracts from traditionally used medicinal plants of Pakistan
  86. Effect of calcium lactate in standard diet on selected markers of oxidative stress and inflammation in ovariectomized rats
  87. Identification of crucial salivary proteins/genes and pathways involved in pathogenesis of temporomandibular disorders
  88. Zirconium-modified attapulgite was used for removing of Cr(vi) in aqueous solution
  89. The stress distribution of different types of restorative materials in primary molar
  90. Reducing surface heat loss in steam boilers
  91. Deformation behavior and formability of friction stir processed DP600 steel
  92. Synthesis and characterization of bismuth oxide/commercial activated carbon composite for battery anode
  93. Phytochemical analysis of Ziziphus jujube leaf at different foliar ages based on widely targeted metabolomics
  94. Effects of in ovo injection of black cumin (Nigella sativa) extract on hatching performance of broiler eggs
  95. Separation and evaluation of potential antioxidant, analgesic, and anti-inflammatory activities of limonene-rich essential oils from Citrus sinensis (L.)
  96. Bioactivity of a polyhydroxy gorgostane steroid from Xenia umbellata
  97. BiCAM-based automated scoring system for digital logic circuit diagrams
  98. Analysis of standard systems with solar monitoring systems
  99. Structural and spectroscopic properties of voriconazole and fluconazole – Experimental and theoretical studies
  100. New plant resistance inducers based on polyamines
  101. Experimental investigation of single-lap bolted and bolted/bonded (hybrid) joints of polymeric plates
  102. Investigation of inlet air pressure and evaporative cooling of four different cogeneration cycles
  103. Review Articles
  104. Comprehensive review on synthesis, physicochemical properties, and application of activated carbon from the Arecaceae plants for enhanced wastewater treatment
  105. Research progress on speciation analysis of arsenic in traditional Chinese medicine
  106. Recent modified air-assisted liquid–liquid microextraction applications for medicines and organic compounds in various samples: A review
  107. An insight on Vietnamese bio-waste materials as activated carbon precursors for multiple applications in environmental protection
  108. Antimicrobial activities of the extracts and secondary metabolites from Clausena genus – A review
  109. Bioremediation of organic/heavy metal contaminants by mixed cultures of microorganisms: A review
  110. Sonodynamic therapy for breast cancer: A literature review
  111. Recent progress of amino acid transporters as a novel antitumor target
  112. Aconitum coreanum Rapaics: Botany, traditional uses, phytochemistry, pharmacology, and toxicology
  113. Corrigendum
  114. Corrigendum to “Petrology and geochemistry of multiphase post-granitic dikes: A case study from the Gabal Serbal area, Southwestern Sinai, Egypt”
  115. Corrigendum to “Design of a Robust sliding mode controller for bioreactor cultures in overflow metabolism via an interdisciplinary approach”
  116. Corrigendum to “Statistical analysis on the radiological assessment and geochemical studies of granite rocks in the north of Um Taghir area, Eastern Desert, Egypt”
  117. Corrigendum to “Aroma components of tobacco powder from different producing areas based on gas chromatography ion mobility spectrometry”
  118. Corrigendum to “Mechanical properties, elastic moduli, transmission factors, and gamma-ray-shielding performances of Bi2O3–P2O5–B2O3–V2O5 quaternary glass system”
  119. Erratum
  120. Erratum to “Copper(ii) complexes supported by modified azo-based ligands: Nucleic acid binding and molecular docking studies”
  121. Special Issue on Applied Biochemistry and Biotechnology (ABB 2021)
  122. Study of solidification and stabilization of heavy metals by passivators in heavy metal-contaminated soil
  123. Human health risk assessment and distribution of VOCs in a chemical site, Weinan, China
  124. Preparation and characterization of Sparassis latifolia β-glucan microcapsules
  125. Special Issue on the Conference of Energy, Fuels, Environment 2020
  126. Improving the thermal performance of existing buildings in light of the requirements of the EU directive 2010/31/EU in Poland
  127. Special Issue on Ethnobotanical, Phytochemical and Biological Investigation of Medicinal Plants
  128. Study of plant resources with ethnomedicinal relevance from district Bagh, Azad Jammu and Kashmir, Pakistan
  129. Studies on the chemical composition of plants used in traditional medicine in Congo
  130. Special Issue on Applied Chemistry in Agriculture and Food Science
  131. Strip spraying technology for precise herbicide application in carrot fields
  132. Special Issue on Pharmacology and Metabolomics of Ethnobotanical and Herbal Medicine
  133. Phytochemical profiling, antibacterial and antioxidant properties of Crocus sativus flower: A comparison between tepals and stigmas
  134. Antioxidant and antimicrobial properties of polyphenolics from Withania adpressa (Coss.) Batt. against selected drug-resistant bacterial strains
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  136. Chemical composition and in vitro and in vivo biological assortment of fixed oil extracted from Ficus benghalensis L.
  137. A review of the pharmacological activities and protective effects of Inonotus obliquus triterpenoids in kidney diseases
  138. Ethnopharmacological study of medicinal plants in Kastamonu province (Türkiye)
  139. Protective effects of asperuloside against cyclophosphamide-induced urotoxicity and hematotoxicity in rats
  140. Special Issue on Essential Oil, Extraction, Phytochemistry, Advances, and Application
  141. Identification of volatile compounds and antioxidant, antibacterial, and antifungal properties against drug-resistant microbes of essential oils from the leaves of Mentha rotundifolia var. apodysa Briq. (Lamiaceae)
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