Volume 33, Issue 3

N-acetylcysteine (NAC) is considered as the body’s major antioxidant molecules with diverse biological properties. In this review, the pharmacokinetics, safety and efficacy report on both the preclinical and clinical summary of NAC is discussed. Both in vitro and in vivo preclinical studies along with the clinical data have shown that NAC has enormous biological properties. NAC is used in the treatment of acetaminophen poisoning, diabetic nephropathy, Alzheimer’s disease, schizophrenia, and ulcerative colitis, etc. Numerous analytical techniques, for instance, UPLC, LC-MS, HPLC, RP-IPC are primarily employed for the estimation of NAC in different single and fixed-dose combinations. The molecular docking studies on NAC demonstrate the binding within Sudlow’s site-I hydrogen bonds and formation of NAC and BSA complexes. Various hydrophobic and hydrophilic amino acids generally exist in making contact with NAC as NAC-BSA complexes. Docking studies of NAC with the active site of the urease exposed an O-coordinated bond through nickel 3002 and a hydrogen bond through His-138. NAC and its analogs also made the allosteric pockets that helped to describe almost all favorable pose for the chaperone in a complex through the protein. Thus, we intended to highlight the several health benefits of this antioxidant compound and applications in pharmaceutical product development.

The rising episodes of deadly heat waves have intensified the need for a heat protection strategy. The Unani system of medicine offers ways to stay healthy in different climatic conditions. Hence, this article aims to discuss the applicability of health protection measures suggested by Unani scholars for hot weather conditions in the light of current researches. The manual literature survey of classical Unani texts was conducted to collect information on health safety measures for hot weather. A substantial search of scientific databases such as “Google Scholar” and “Medline” for proposed measures in combination with “heat-stroke”, “heat exhaustion” and “heat rash” was also conducted to identify their possible activity in heat-related illnesses. The guidelines for summer seasons in the classical Unani literature are described under the title tadābīr-i-mavsam. Unani scholars have discussed in detail the pathophysiological effects of heat and the measures to stay healthy by regulating the body system through lifestyle, diet and herbs. Most of the measures proposed by them are backed up by evidences. However, some measures have not yet been evaluated for their therapeutic or prophylactic efficacy in heat-related illnesses. On the basis of findings, the authors advocate the adoption of evidence-based measures and propose further investigation of those measures that are not well supported by the evidence or have not yet been evaluated.

Objectives Human exposure to heavy metals and pesticides is a worldwide major health problem. These environmental pollutants have been considered as the most neurotoxic agents and responsible to causing neurological toxicity. Plant-based therapeutic supplement may be used in the event of toxicity. Citrus limon contains several useful bioactive ingredients including flavonoids, dietary fiber, carotenoids, vitamins, pectin, minerals, and essential oils, which are responsible for its therapeutic potential. In the present investigation, we have studied the toxicity of heavy metals such as lead (Pb) and a carbamate pesticide such as cartap (Cp) on rat brain acetylcholinesterase (AChE). Methods The chemical characterization of C. limon involved determination of total antioxidants and 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical scavenging activity using known methods. The AChE activity and its kinetic characterization were performed by assaying the enzyme activity at varying substrate concentrations, pH, temperature, and time of reaction. Its different kinetic parameters such as K i , V max , K m , K cat , and K cat / K m were determined by using standard procedures. The amelioration potential of the extract was evaluated on the neurotransmission system of rat brain AChE treated with Pb, Cp, and their combination (Pb–Cp), considering their 50% inhibitory concentration (IC 50 ) values. Results The optimal activity of rat brain AChE was recorded at 25 µg of protein, pH of 7.4, substrate concentration [S] of 0.5 mM, and temperature of 37.4–40°C. The enzyme was stable for 10 min when incubated at 37.4 °C in vitro . The enzyme displayed 70% of its activity remaining even after 160 min of incubation in this condition. It may be stable up to 1 month when stored at −20°C. The IC 50 values for Pb, Cp, and Pb–Cp were found to be 75, 2.9, and 5 mM, respectively. Pb, Cp, and Pb–Cp inhibited the activity of rat brain AChE in the noncompetitive, mixed, and uncompetitive manners, respectively, with their respective K i values to be 675, 2.37, and 22.72 mM. Conclusions The results indicated that the Pb and Cp were able to cause significant alterations in the level and properties of AChE. However, the introduction of lemon juice on Pb- and Cp-treated AChE indicated protection of its activity from their adverse effects. The results may be useful in prospective therapeutic applications of lemon juice or as a food supplement to protect mammalian systems from adverse effects of these toxicants.

Objectives Exposure to arsenic and hexavalent chromium is a major public health concern especially in the developing part of the world and there is paucity of information on reliable treatment modalilities. It is in this regard that this study evaluates the efficacy of methanol leaf extract of Rauvolfia vomitoria (MRV) when used as pretreatment agent against potassium dichromate (K 2 Cr 2 O 7 ) and sodium arsenite (NaAsO 2 ) exposure. Methods Swiss albino mice between 7 and 10 weeks old were divided into eight cohorts of five animals each. Treatment groups consisted of a distilled water control, MRV alone (275 mg/kg po daily), K 2 Cr 2 O 7 (12.0 mg/kg, single ip injection) +/− MRV pretreatment, NaAsO 2 (2.5 mg/kg, single ip injection) +/− MRV pretreatment, Na 2 AsO 2  + K 2 Cr 2 O 7 +/− MRV pretreatment. MRV was given for seven consecutive days, while K 2 Cr 2 O 7 and NaAsO 2 were injected on day seven of the experiment. The frequency of micronucleated polychromatic erythrocytes (mPCEs) was determined in bone marrow cells, while aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were assessed in the plasma. Hepatic glutathione (GSH), malondialdehyde (MDA), catalase (CAT) and glutathione-S-transferase (GST) levels were also determined. Results The NaAsO 2 and K 2 Cr 2 O 7 significantly (p<0.05) increased mPCE formation, AST, ALT, and CAT when compared with the control. Simultaneous exposure to NaAsO 2 and K 2 Cr 2 O 7 further increased the levels of the markers. Furthermore, GSH and GST were significantly reduced by NaAsO 2 or K 2 Cr 2 O 7 or their combination. Pretreatment with MRV reversed the markers towards that of control. Conclusions Methanol extract of Rauvolfia vomitoria may therefore ameliorate NaAsO 2 and K 2 Cr 2 O 7 -induced toxicities via reduction of oxidative stress and fortification of anti-oxidant system.

Objectives The threat to human health or the surroundings by the use of artificial fruit ripening agents has become a global concern. Calcium carbide (CaC 2 ) and ethylene glycol (EG) are the two widely using ripening agents. The present study evaluates the toxic effect of chronic exposures of CaC 2 and EG in rats. Methods CaC 2 and EG were administered to the rats for 180 days orally. The alterations in oxido-reduction status, haematological, biochemical and histopathological parameters were analysed. Arsenic content in CaC 2 and animal samples were detected by atomic absorption spectrometer and phosphorus by molybdate-UV method. Results At chronic doses, there were no significant alterations in haematological and biochemical parameters except in creatinine level especially by EG. However, histological details revealed microvesicular fatty change in liver, corpuscles degeneration in kidney and lymphocytes infiltration in various tissues. In intestine, the mucosal lesion scoring was found high (p<0.01). SOD and CAT activities and GSH level was reduced significantly by CaC 2 administration (p<0.01). Arsenic and phosphorus detected is above the toxic level: 7.222 and 13.91 mg/dL in CaC 2 , 1.634 and 6.22 mg/dL in blood and 0.563 and 6.99 mg/dL in liver, respectively. Conclusions The study suggests that the industrial grade CaC 2 and EG induce systemic toxicity to rats and the liver is the most susceptible organ. The CaC 2 and EG toxicity is mediated through the upset of redox balance and subsequent inflammatory responses. This could be due to the presence of arsenic and phosphorus contents that detected above the normal level in the industrial grade CaC 2 .

Objectives Vanadium has been reported to possess relevant therapeutic properties such as anti-diabetic and anti-tumoral. This study aimed at determining the effects of vanadium on experimentally induced colitis in rats. Methods Forty-five male Wistar rats (103 ± 3.90 g, n=15) were used for this study and were divided into three groups. Group 1 (Untreated control) had nothing added to their drinking, while groups 2 and 3 received sodium metavanadate at a dose of 50 and 200 mg/L respectively in their drinking water for 10 weeks. Colitis was thereafter induced by intra colonic administration of 1.50 mL of 6% acetic acid. Animals were sacrificed on day 0 (pre-induction), three- and seven-days post induction. Blood samples were collected for haematological variables and the distal 8 cm of the colon was collected for macroscopic, histological and biochemical (malondialdehyde-MDA, superoxide dismutase-SOD, catalase-CAT, glutathione peroxidase- GPx and nitrite concentration- NO) assessment. Results Low dose vanadium proved beneficial in ameliorating acetic acid-induced colitis by improving both histopathological and haematological changes. Gross observation showed a faster healing rate in vanadium treated groups (50 and 200 mg/L) compared with untreated control at day 3 (40 and 26.20 vs. 2.50%) and day 7 (80 and 66.70 vs. 42%) respectively. Vanadium also appears to exert its beneficial effects on acetic acid-induced colitis via up regulation of antioxidant enzymes (SOD, CAT, GPx) and NO while decreasing the over production of MDA. Conclusions Vanadium at small concentration functions as an essential trace element and may be able to promote healing process during ulcerative colitis.

Objectives This study examined the possible protective roles of exogenous glycine (Gly) and L-Arginine ( l -Arg) against Diclofenac (DIC)-induced gastro-duodenal damage in rats. Methods Rats were divided into Group A (control), Group B (DIC group) and Groups C–F which were pre-treated for five days with Gly1 (250 mg/kg), Gly2 (500 mg/kg), l -Arg1 (200 mg/kg) and l -Arg2 (400 mg/kg), respectively, before co-treatment with DIC for another three days. Hematological, biochemical and histopathological analyses were then carried out. Results DIC produced significant (p<0.05) reduction in PCV (13.82%), Hb (46.58%), RBC (30.53%), serum total protein (32.72%), albumin (28.44%) and globulin (38.01%) along with significant (p<0.05) elevation of serum MPO activity (83.30%), when compared with control. In addition, DIC increased gastric H 2 O 2 and MDA levels by 33.93 and 48.59%, respectively, while the duodenal levels of the same parameters increased by 19.43 and 85.56%, respectively. Moreover, SOD, GPx and GST activities in the DIC group were significantly (p<0.05) reduced in the stomach (21.12, 24.35 and 51.28%, respectively) and duodenum (30.59, 16.35 and 37.90%, respectively), compared to control. Treatment with Gly and l -Arg resulted in significant amelioration of the DIC-induced alterations although l -Arg produced better amelioration of RBC (29.78%), total protein (10.12%), albumin (9.93%) and MPO (65.01%), compared to the DIC group. The protective effects of both amino acids against oxidative stress parameters and histological lesions were largely similar. Conclusions The data from this study suggest that Gly or l -Arg prevented DIC-induced gastro-duodenal toxicity and might, therefore be useful in improving the therapeutic index of DIC.

Objectives Lead primarily affects male reproductive functions via hormonal imbalance and morphological damage to the testicular tissue with significant alteration in sperm profile and oxidative markers. Though, different studies have reported that Cocos nucifera L . oil has a wide range of biological effects, this study aimed at investigating the effect of Cocos nucifera L. oil on lead acetate-induced reproductive toxicity in male Wistar rats. Methods Twenty (20) sexually matured male Wistar rats (55–65 days) were randomly distributed into four groups (n=5). Group I (negative control)—distilled water orally for 56 days, Group II (positive control)—5 mg/kg bwt lead acetate intraperitoneally (i.p.) for 14 days, Group III—6.7 mL/kg bwt Cocos nucifera L . oil orally for 56 days and Group IV—lead acetate intraperitoneally (i.p.) for 14 days and Cocos nucifera L . oil for orally for 56 days. Rats were sacrificed by diethyl ether, after which the serum, testis and epididymis were collected and used for semen analysis, biochemical and histological analysis. Results The lead acetate significantly increases (p<0.05) testicular and epididymal malondialdehyde (MDA) levels, while a significant reduction (p<0.05) in sperm parameters, organ weight, testosterone and luteinizing hormone was observed when compared with the negative control. The coadministration of Cocos nucifera oil with lead acetate significantly increases (p<0.05) testosterone, luteinizing hormone, sperm parameters and organ weight, with a significant decrease (p<0.05) in MDA levels compared with positive control. Histological analysis showed that lead acetate distorts testicular cytoarchitecture and germ cell integrity while this was normalized in the cotreated group. Conclusions Cocos nucifera oil attenuates the deleterious effects of lead acetate in male Wistar rats, which could be attributed to its polyphenol content and antioxidant properties.

Objectives The development of approaches to the treatment of neurodegenerative diseases caused by alcohol abuse by targeted pharmacological regulation of intracellular signaling transduction of progenitor cells of nerve tissue is promising. We studied peculiarities of participation of NF-кB-, сАМР/РКА-, JAKs/STAT3-, ERK1/2-, p38-pathways in the regulation of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in the simulation of ethanol-induced neurodegeneration in vitro and in vivo . Methods In vitro , the role of signaling molecules (NF-кB, сАМР, РКА, JAKs, STAT3, ERK1/2, p38) in realizing the growth potential of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in ethanol-induced neurodegeneration modeled in vitro and in vivo was studied. To do this, the method of the pharmacological blockade with the use of selective inhibitors of individual signaling molecules was used. Results Several of fundamental differences in the role of certain intracellular signaling molecules (SM) in proliferation and specialization of NSC and NCP have been revealed. It has been shown that the effect of ethanol on progenitors is accompanied by the formation of a qualitatively new pattern of signaling pathways. Data have been obtained on the possibility of stimulation of nerve tissue regeneration in ethanol-induced neurodegeneration by NF-кB and STAT3 inhibitors. It has been found that the blockage of these SM stimulates NSC and NCP in conditions of ethanol intoxication and does not have a «negative» effect on the realization of the growth potential of intact progenitors (which will appear de novo during therapy). Conclusions The results may serve as a basis for the development of fundamentally new drugs to the treatment of alcoholic encephalopathy and other diseases of the central nervous system associated with alcohol abuse.

Objectives Sepsis is a clinical crisis which has been considered as one of the important causes of mortality across the world. We hypothesized that modulation of hyper-inflammatory phase of sepsis pathophysiology can lead to protective effects on survival outcome. Glatiramer acetate (GA) is a neuroprotective drug commonly used in multiple sclerosis (MS). GA is characterized by immunom activity via regulation of innate and adaptive immunity. This study was designed to evaluate the acute treatment with GA on initial inflammatory response-induced mortality in septic mice. Methods Cecal ligation and puncture (CLP) model was operated on male mice as a model of Polymicrobial sepsis. GA was administrated intraperitoneally after the sepsis induction at doses of 0.5, 1, and 2 mg/kg in three treatment groups. To investigate the effect of GA on short-term survival, septic mice were observed during 72 h after CLP. Serum levels of TNF-α, IL-1β, and IL-6 as pro-inflammatory cytokines and also IL-10 as a critical anti-inflammatory cytokine were analysed. To consider sepsis-induced acute kidney injury, renal functional biomarkers and histopathological changes was assessed. Results GA treatment significantly improved survival rate at doses of 1, and 2 mg/kg. Survival improvement was accompanied by remarkable reduction in the pro-inflammatory cytokines and enhanced production of IL-10. GA showed to have protective effects on renal function as well. Conclusions Immunomodulatory and anti-inflammatory properties of GA resulted in increase in survival rate and decrease in inflammatory markers in mice model of cecal ligation and puncture–induced sepsis.

Objectives Ciprofloxacin (CIPRO) is a fluroquinolone class antibiotic used commonly for the treatment of various acute and chronic bacterial infections. However, recently there is increase in the case reports of CIPRO-induced Cutaneous Adverse Drug Reactions (CADRs). We aim to systematically review all the descriptive studies of CIPRO induced CADRs. Methods Medline (via PubMed) was searched without any language or date restriction from inception to March 2019 using search terms of “Ciprofloxacin” and “Cutaneous reactions.” We included only the descriptive studies, which elucidate the CADRs experienced by the patients following the administration of CIPRO. Two reviewers involved in study selection, data extraction and quality assessment of the included studies. Discrepancies were resolved by consensus between the reviewers. Results Thirty-nine studies (out of 446) were found to be eligible for the final inclusion. The dose of CIPRO among the included studies was ranging from 500 to 1,000 mg/day and duration of treatment was between 7 and 10 days. The most common CADRs observed were toxic epidermal necrolysis, Stevens–Johnson syndrome, fixed drug eruptions, bullous fixed drug reaction, acute generalized pustulosis, erythema multiforme, drug rash with eosinophilia and systemic symptoms and erythema nodosum. Conclusions Management of the CIPRO-induced CADRs is recommended with the complete cessation of the CIPRO, followed by supportive management with oral or topical glucocorticoids, emollients, and topical moisturizers. CIPRO is likely to cause CADRs, physicians should be vigilant while prescribing it to the patients.

Objectives The role of aqueous extract of Adansonia digitata was investigated against cadmium chloride-induced testicular damage in Wistar Rats. Methods Thirty (30) male Wistar Rats weighing (150–170) were divided into six groups (n=5). Group A served as control and received oral administration of phosphate buffer saline; group B received 800 mg/kg A. digitata only; group C were injected intraperitoneally with single dose 2 mg/kg b.w cadmium chloride; group D were injected intraperitoneally with single dose 2 mg/kg b.w cadmium chloride and treated with 800 mg/kg aqueous extract of A. digitata ; group E received 300 mg/kg vitamin E only; group F were injected intraperitoneally with single dose 2 mg/kg b.w cadmium chloride and treated with 300 mg/kg vitamin E. After 21 days, the animals were sacrificed by cervical dislocation, the testes were excised fixed in Bouins fluids for histological analysis and the other homogenized in 5% sucrose solution for determination of tissue malondialdehyde (MDA) and antioxidant enzyme activity, biochemical assay. Results The group treated with cadmium chloride plus A. digitata caused significant decrease in MDA levels with significant increase (p<0.05) in antioxidant activities and biochemical enzymes when compared to cadmium chloride only group. Conclusions Aqueous extract of A. digitata appears to have ameliorative effect against cadmium chloride-induced testicular damage. This could be attributed to the presence of polyphenolic compound.

Objectives The human body physiology rapidly changes and adapt to several environmental stimuli, including light. Abnormal artificial light exposures have been shown to affect sleep cycle, cognition, and mood. Although studies have reported inconsistent effects of short-term or constant long-term light exposures, human exposures to artificial lights occur at varying, unpredictable times and duration daily. Here, we studied the effects of long-term unpredictable light exposure on learning, memory, oxidative status, and associated cytokines in rats. Methods Artificial lighting was provided using an array of white light-emitting diodes coupled to a microcontroller that switches them on or off at unpredictable times and duration (light intensity = 200 ± 20 lx). Within the last eight days of 40 days exposure, animals were subjected to open field test, Morris water maze, and novel object recognition behavioral paradigms. Brain levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase, reduced glutathione (GSH), glutathione S-transferase (GST), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) were assayed. Results Exposed rats showed impaired spatial learning and memory (p<0.05), but no changes in object recognition memory or locomotor activity. Oxidative stress analyses also revealed significant changes in the concentrations of MDA, SOD, catalase, and GSH levels (p<0.05), not GST. Similarly, there was an increased TNF-α expression (p<0.05), not VEGF. Conclusions We conclude that oxidative stress is involved in memory impairment in rats exposed to prolonged unpredictable lights, which again suggests the detrimental effects of extended light exposure on the nervous system.

Objectives Cardiovascular diseases (CVDs) are highly prevalent in various countries, and heart failure accounts for the majority of deaths. The present study focuses on determining the protective effect of ethanol extract of leaves of Tamarindus indica (TIEE) by in vitro and in vivo methods. Methods In vitro cardiotonic activity was determined using Langendorff’s heart perfusion assembly. In vivo studies were performed using Doxorubicin (1.5 mg/kg, i.p for seven days) induced cardiotoxicity in rats. These animals were simultaneously treated with the TIEE at a low dose (200 mg/kg, p.o), high dose (400 mg/kg, p.o) and standard drug Digoxin (100 μg/kg, p.o) for seven days. At the end of the study, various parameters like electrocardiogram (ECG) recording, serum levels of serum glutamic pyruvic transaminase (SGPT), lactate dehydrogenase (LDH), creatinine phosphokinase (CPK), and presence of cardiac troponin (cTnI) were determined . Isolated hearts were subjected to histopathological studies. Results The TIEE at a concentration of 60 μg/mL showed a significant cardiotonic effect in vitro that was evident by increased force of contraction, heart rate, and cardiac output. In vivo studies revealed that the TIEE decreased the prolongation of QT and RR interval of ECG, lowered the serum enzyme levels like LDH, CPK indicating cardiac protection, and the same was established by the absence of cTnI in blood. Histopathological examinations of heart tissue sections showed improved architecture in the treatment groups when compared with diseased groups. Conclusions The study revealed the cardioprotective activity of T. indica leaf extract by both in vitro and in vivo methods.