Neuroprotective role of 6-Gingerol-rich fraction of Zingiber officinale (Ginger) against acrylonitrile-induced neurotoxicity in male Wistar rats
-
Ebenezer Olatunde Farombi
,
Amos Olalekan Abolaji
Abstract
Background
Acrylonitrile (AN) is a neurotoxin that is widely used to manufacture synthetic fibres, plastics and beverage containers. Recently, we reported the ameliorative role of 6-gingerol-rich fraction from Zingiber officinale (Ginger, GRF) on the chlorpyrifos-induced toxicity in rats. Here, we investigated the protective role of GRF on AN-induced brain damage in male rats.
Methods
Male rats were orally treated with corn oil (2 mL/kg, control), AN (50 mg/kg, Group B), GRF (200 mg/kg, Group C), AN [50 mg/kg+GRF (100 mg/kg) Group D], AN [(50 mg/kg)+GRF (200 mg/kg) Group E] and AN [(50 mg/kg)+N-acetylcysteine (AC, 50 mg/kg) Group F] for 14 days. Then, we assessed the selected markers of oxidative damage, antioxidant status and inflammation in the brain of rats.
Results
The results indicated that GRF restored the AN-induced elevations of brain malondialdehyde (MDA), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and Nitric Oxide (NO) levels. GRF also prevented the AN-induced depletion of brain glutathione (GSH) level and the activities of Glutathione S-transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in rats (p<0.05). Furthermore, GRF prevented the AN-induced cerebral cortex lesion and increased brain immunohistochemical expressions of Caspases-9 and -3.
Conclusions
Our data suggest that GRF may be a potential therapeutic agent in the treatment of AN-induced model of brain damage.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Cole P, Mandel JS, Collins JJ. Acrylonitrile and cancer: a review of the epidemiology. Regul Toxicol Pharmacol 2008;52:342–51.10.1016/j.yrtph.2008.09.004Search in Google Scholar PubMed
2. Rongzhu L, Suhua W, Guangwei X, Chunlan R, Fangan H, Suxian C, et al. Effects of acrylonitrile on antioxidant status of different brain regions in rats. Neurochem Int 2009;55:552–7.10.1016/j.neuint.2009.05.009Search in Google Scholar PubMed
3. Rubio R, Galceran MT, Rauret G. Nitriles and isonitriles as interferents in cyanide determination in polluted water. Analyst 1990;115:959–63.10.1039/an9901500959Search in Google Scholar PubMed
4. Mohamadin AM, El-Demerdash E, El-Beshbishy HA, Abdel-Naim AB. Acrylonitrile-induced toxicity and oxidative stress in isolated rat colonocytes. Environ Toxicol Pharmacol 2005;19:371–7.10.1016/j.etap.2004.09.004Search in Google Scholar PubMed
5. OSHA (Occupational Safety and Health Administration). Notice issuing final standard for acrylonitrile. Federal Register 1978;43:457–62.Search in Google Scholar
6. Gumperlein I, Fischer E, Dietrich-Gumperlein G, Karrasch S, Nowak D, Jorres RA, et al. Acute health effects of desktop 3D printing (fused deposition modeling) using acrylonitrile butadiene styrene and polylactic acid materials: an experimental exposure study in human volunteers. Indoor Air 2018;28:611–23.10.1111/ina.12458Search in Google Scholar PubMed
7. Zimmerman SD, Marsh GM, Youk AO, Talbot E. Evaluation of potential confounding by smoking in the presence of misclassified smoking data in a cohort study of workers exposed to acrylonitrile. J Occup Environ Med 2015;57:146–51.10.1097/JOM.0000000000000386Search in Google Scholar PubMed
8. Tarskikh MM, Klimatskaia LG. Nervous system disorders in workers engaged into acrylonitrile production. Med Tr Prom Ekol 2008;10:12–5.Search in Google Scholar
9. Marsh GM, Zimmerman SD. Mortality among chemical plant workers exposed to acrylonitrile: 2011 follow-up. J Occup Environ Med 2015;57:134–45.10.1097/JOM.0000000000000369Search in Google Scholar PubMed
10. Kamendulis LM, Jiang J, Xu Y, Klaunig JE. Induction of oxidative stress and oxidative damage in rat glial cells by acrylonitrile. Carcinogenesis 1999;20:1555–60.10.1093/carcin/20.8.1555Search in Google Scholar PubMed
11. Ghanayern BI, Nyska A, Haseman JK, Bucher JR. Acrylonitrile is a multisite carcinogen in male and female B6C3F1 mice. Toxicol Sci 2002;68:59–68.10.1093/toxsci/68.1.59Search in Google Scholar PubMed
12. Williams GM, Kobets T, Duan JD, Iatropoulos MJ. Assessment of DNA binding and oxidative DNA damage by acrylonitrile in two rat target tissues of carcinogenicity: implications for the mechanism of action. Chem Res Toxicol 2017;30:1470–80.10.1021/acs.chemrestox.7b00105Search in Google Scholar PubMed
13. Parent A, Carpenter MB. Carpenter’s human neuroanatomy. Williams & Wilkins, 1995. ISBN 978-0-683-06752–1.Search in Google Scholar
14. Gagnaire F, Marignac B, Baonnet P. Relative neurotoxicological properties of five unsaturated aliphatic nitriles in rats. J Appl Toxicol 1998;18:25–31.10.1002/(SICI)1099-1263(199801/02)18:1<25::AID-JAT466>3.0.CO;2-VSearch in Google Scholar
15. Caito SW, Yu Y, Aschner M. Differential inflammatory response to acrylonitrile in rat primary astrocytes and microglia. Neurotoxicology 2014;42:1–7.10.1016/j.neuro.2014.02.006Search in Google Scholar
16. Esmat A, El-Demerdash E, El-Mesallamy H, Abdel-Naim AB. Toxicity and oxidative stress of acrylonitrile in rat primary glial cells: preventive effects of N-acetylcysteine. Toxicol Lett 2007;171:111–8.10.1016/j.toxlet.2007.05.001Search in Google Scholar
17. El-Sayed SM, Abo-Salem AO, Abd-Ellah MF, Abd-Alla GF. Hesperidin, an antioxidant flavonoid, prevents acrylonitrile-induced oxidative stress in rat brain. J Biochem Mol Toxicol 2008;22:268–73.10.1002/jbt.20237Search in Google Scholar
18. Pu X, Kamendulis LM, Klaunig JE. Acrylonitrile-induced oxidative stress and oxidative DNA damage in male Sprague-Dawley rats. Toxicol Sci 2009;111:64–71.10.1093/toxsci/kfp133Search in Google Scholar
19. Guangwei X, Rongzhu L, Wenrong X, Suhua W, Xiaowu Z, Shizhong W, et al. Curcumin pretreatment protects against acute acrylonitrile-induced oxidative damage in rats. Toxicology 2010;267:140–6.10.1016/j.tox.2009.11.001Search in Google Scholar
20. Jakubowski M, Linhart I, Pielas G, Kopecky J. 2-Cyanoethylmercapturic acid (CEMA) in the urine as a possible indicator of exposure to acrylonitrile. Brit J Ind Med 1987;44:834–40.10.1136/oem.44.12.834Search in Google Scholar
21. Zheng J, Zhou Y, Li Y, Xu DP, Li S, Li HB. Spices for prevention and treatment of cancers. Nutrients 2016;8:495–530.10.3390/nu8080495Search in Google Scholar
22. Samad MB, Mohsin MN, Razu BA, Hossain MT, Mahzabeen S, Unnoor N, et al. [6]-Gingerol, from Zingiber officinale, potentiates GLP-1 mediated glucose-stimulated insulin secretion pathway in pancreatic β-cells and increases RAB8/RAB10-regulated membrane presentation of GLUT4 transporters in skeletal muscle to improve hyperglycemia in Leprdb/db type 2 diabetic mice. BMC Complement Altern Med 2017;17:395.10.1186/s12906-017-1903-0Search in Google Scholar
23. Dugasani S, Pichikac MR, Nadarajahc VD, Balijepalli BK, Tandra S, Korlakunta JN. Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol. J Ethnopharmacol 2010;127:515–20.10.1016/j.jep.2009.10.004Search in Google Scholar
24. El-Ghorab AH, Nauman M, Anjum FM, Hussain S, Nadeem M. A comparative study on chemical composition and antioxidant activity of ginger (Zingiber officinale) and cumin (Cuminum cyminum). J Agric Food Chem 2010;58:8231–7.10.1021/jf101202xSearch in Google Scholar
25. Ajayi BO, Adedara IA, Farombi EO. Pharmacological activity of 6-gingerol in dextran sulphate sodium-induced ulcerative colitis in BALB/c mice. Phytother Res 2015;29:566–72.10.1002/ptr.5286Search in Google Scholar
26. Abolaji AO, Ojo M, Afolabi TT, Arowoogun MD, Nwawolor D, Farombi EO. Protective properties of 6-gingerol-rich fraction from Zingiber officinale (Ginger) on chlorpyrifos-induced oxidative damage and inflammation in the brain, ovary and uterus of rats. Chem Biol Interact 2017;270:15–23.10.1016/j.cbi.2017.03.017Search in Google Scholar
27. Almada da Silva J, Becceneri AB, Sanches Mutti H, Moreno Martin AC, Fernandes da Silva MF, fernandes JB, et al. Purification and differential biological effects of ginger-derived substances on normal and tumour cell lines. J Chromatogr B 2012;903: 157–62.10.1016/j.jchromb.2012.07.013Search in Google Scholar
28. Salihu M, Ajayi BO, Adedara IA, de Souza D, Rocha JB, Farombi EO. 6-Gingerol-rich fraction from Zingiber officinale ameliorates carbendazim-induced endocrine disruption and toxicity in testes and epididymis of rats. Andrologia 2016;49. doi:10.1111/and.12658.10.1111/and.12658Search in Google Scholar
29. De Vries N, De Flora S. N-acetyl-l-cysteine. J Cell Biochem 1993;17:270–7.10.1002/jcb.240531040Search in Google Scholar
30. Salihu M, Ajayi BO, Adedara IA, Farombi EO. 6-Gingerol-rich fraction from Zingiber officinale prevents hematotoxicity and oxidative damage in kidney and liver of rats exposed to carbendazim. J Diet Suppl 2016;13:433–48.10.3109/19390211.2015.1107802Search in Google Scholar
31. Abdelmagid SM, Barr AE, Rico M, Amin M, Litvin J, Popoff SN, et al. Performance of repetitive tasks induces decreased grip strength and increased fibrogenic proteins in skeletal muscle: role of force and inflammation. PLoS One 2012;7:e38359.10.1371/journal.pone.0038359Search in Google Scholar
32. Fraenkel GS, Gunn DL. The orientation of animals – kineses, taxes and compass reactions, Expanded Edition. Dover Publications Inc., 1961:384.Search in Google Scholar
33. Misra HP, Fridovich I. The role of superoxide anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972;247:3170–5.10.1016/S0021-9258(19)45228-9Search in Google Scholar
34. Clairborne A. Catalase activity. In: Greewald AR, editor. Handbook of methods for oxygen radical research. Boca Raton, FL: CRC Press, 1995:237–42.Search in Google Scholar
35. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science 1973;179:588–90.10.1126/science.179.4073.588Search in Google Scholar PubMed
36. Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR. Bromobenzene induced liver necrosis: protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 1974;74:151–69.10.1159/000136485Search in Google Scholar
37. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferase, the first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130–9.10.1016/S0021-9258(19)42083-8Search in Google Scholar
38. Buege JA, Aust SD. Microsomal lipid peroxidation. Method Enzymol 1978;30:302–10.10.1016/S0076-6879(78)52032-6Search in Google Scholar
39. Perez-Severiano F, Santamaria A, Pedraza-Chaverri J, Medina-Campos ON, Rios C, Segovia J. Increased formation of reactive oxygen species, but no changes in glutathione peroxidase activity in striata of mice transgenic for the Huntington’s disease mutation. Neurochem Res 2004;29:729–33.10.1023/B:NERE.0000018843.83770.4bSearch in Google Scholar
40. Abolaji AO, Kamdem JP, Lugokenski TH, Nascimento TK, Waczuk EP, Farombi EO, et al. Involvement of oxidative stress in 4-vinylcyclohexene-induced toxicity in Drosophila melanogaster. Free Radic Biol Med 2014;71:99–108.10.1016/j.freeradbiomed.2014.03.014Search in Google Scholar
41. Bradford MM. Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–54.10.1016/0003-2697(76)90527-3Search in Google Scholar
42. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite and (15N) nitrate in biological fluids. Anal Biochem 1982;126:131–8.10.1016/0003-2697(82)90118-XSearch in Google Scholar
43. Bancroft JD, Gamble M. Theory and practice of histology techniques, 6th ed. Churchill Livingstone: Elsevier, 2008:83–134.10.1016/B978-0-443-10279-0.50013-0Search in Google Scholar
44. Plewka D, Kowalczyk AE, Jakubiec-Bartnik B, Morek M, Bogunia E, Kmiec A, et al. Immunohistochemical visualization of pro-inflammatory cytokines and enzymes in ovarian tumours. Folia Histochem Cytobiol 2014;52:124–37.10.5603/FHC.2014.0015Search in Google Scholar PubMed
45. Rongzhu L, Suhua W, Guangwei X, Fangan H, Ziqiang C, Fusheng J, et al. Neurobehavioral alterations in rats exposed to acrylonitrile in drinking water. Hum Exp Toxicol 2007;26:179–84.10.1177/0960327107070563Search in Google Scholar PubMed
46. Abolaji AO, Toloyai PE, Odeleye TD, Akinduro S, Teixeira S, Rocha JB, et al. Hepatic and renal toxicological evaluations of an industrial ovotoxic chemical, 4-vinylcyclohexene diepoxide, in both sexes of Wistar rats. Environ Toxicol Pharmacol 2016;45:28–40.10.1016/j.etap.2016.05.010Search in Google Scholar
47. Sato M, Hirasawa F, Ogata M, Takizawa Y, Kojima H, Yoshida T. Distribution and accumulation of [2,3-14C] acrylonitrile in rat after single injection. Ecotoxicol Environ Saf 1982;6:489–94.10.1016/0147-6513(82)90030-6Search in Google Scholar
48. Weber C, Jakobsen TS, Mortensen SA, Paulsen G, Hølmer G. Effect of dietary coenzyme Q10 as an antioxidant in human plasma. Mol Aspects Med 1994;15:97–102.10.1016/0098-2997(94)90018-3Search in Google Scholar
49. Patel M. Targeting oxidative stress in central nervous system disorders. Trends Pharmacol Sci 2016;37:768–78.10.1016/j.tips.2016.06.007Search in Google Scholar
50. Leng G, Lewalter J. Polymorphism of glutathione S-transferases and susceptibility to acrylonitrile and dimethylsulfate in cases of intoxication. Toxicol Lett 2002;134:209–17.10.1016/S0378-4274(02)00191-1Search in Google Scholar
51. Fennell TR, Kedderis GL, Sumner SC. Urinary metabolites of (1,2,3-13C) acrylonitrile in rats and mice detected by 13C nuclear magnetic resonance spectroscopy. Chem Res Toxicol 1991;4:678–87.10.1021/tx00024a013Search in Google Scholar
52. Ahmed AE, Farooqui YH, Upreti RK, El-Shabrawy O. Distribution and covalent interactions of [1–14C] acrylonitrile in the rat. Toxicology 1982;23:159–75.10.1016/0300-483X(82)90095-6Search in Google Scholar
53. Tanabe K, Kozawa O, Iida H. cAMP/PKA enhances interleukin-1β-induced interleukin-6 synthesis through STAT3 in glial cells. Cell Signal 2016;28:19–24.10.1016/j.cellsig.2015.10.009Search in Google Scholar PubMed
54. Spooren A, Kolmus K, Laureys G, Clinckers R, De Keyser J, Haegeman G, et al. Interleukin-6, a mental cytokine. Brain Res Rev 2011;67:157–83.10.1016/j.brainresrev.2011.01.002Search in Google Scholar PubMed
55. Erta M, Quintana A, Hidalgo J. Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci 2012;8:1254–66.10.7150/ijbs.4679Search in Google Scholar PubMed PubMed Central
56. Thorsteinsdottir S, Gudjonsson T, Nielsen OH, Vainer B, Seidelin JB. Pathogenesis and biomarkers of carcinogenesis in ulcerative colitis. Nat Rev Gastroenterol Hepatol 2011;8:395–404.10.1038/nrgastro.2011.96Search in Google Scholar PubMed
57. Papadakis KA, Targan SR. The role of chemokines and chemokine receptors in mucosal inflammation. Inflamm Bowel Dis 2000;6:303–13.10.1097/00054725-200011000-00007Search in Google Scholar
58. Kuranaga E, Miura M. Nonapoptotic functions of caspases: caspases as regulatory molecules for immunity and cell-fate determination. Trends Cell Biol 2007;17:135–44.10.1016/j.tcb.2007.01.001Search in Google Scholar PubMed
59. D’Amelio M, Cavallucci V, Cecconi F. Neuronal caspase-3 signalling: not only cell death. Cell Death Differ 2010;17:1104–14.10.1038/cdd.2009.180Search in Google Scholar PubMed
60. Lebelt A, Rutkowski R, Och W, Jaczun K, Dziemiańczyk-Pakieła D, Milewski R, et al. Survivin, caspase-3 and MIB-1 expression in astrocytic tumors of various grades. Adv Med Sci 2016;61: 237–43.10.1016/j.advms.2016.02.001Search in Google Scholar PubMed
61. Broughton BR, Reutens DC, Sobey CG. Apoptotic mechanisms after cerebral ischemia. Stroke 2009;40:331–9.10.1161/STROKEAHA.108.531632Search in Google Scholar PubMed
62. Graham RK, Ehrnhoefer DE, Hayden MR. Caspase-6 and neurodegeneration. Trends Neurosci 2011;34:646–56.10.1016/j.tins.2011.09.001Search in Google Scholar PubMed
63. Watcharasit P, Suntararuks S, Visitnonthachai D, Thiantanawat A, Satayavivad J. Acrylonitrile induced apoptosis via oxidative stress in neuroblastoma SH-SY5Y cell. J Appl Toxicol 2010;30:649–55.10.1002/jat.1535Search in Google Scholar PubMed
©2019 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Minireview
- Clinical assessment of arthritic knee pain by infrared thermography
- Original Articles
- Methanol stem bark extract of Adansonia digitata ameliorates chronic unpredictable mild stress-induced depression-like behavior: Involvement of the HPA axis, BDNF, and stress biomarkers pathways
- The protective effect of aqueous extract of Typha capensis rhizomes on cadmium-induced infertility in rats
- The aqueous and methanol extracts of Bambusa vulgaris (Poaceae) improve calcium and phosphorus levels, and bone microstructure in ovariectomized model of osteoporosis
- Assessment of epigenetic changes and oxidative DNA damage in rat pups exposed to polychlorinated biphenyls and the protective effect of curcumin in the prenatal period
- Assessment of heart rate variability for different somatotype category among adolescents
- Neuroprotective role of 6-Gingerol-rich fraction of Zingiber officinale (Ginger) against acrylonitrile-induced neurotoxicity in male Wistar rats
- Antioxidant activity of crude ethanolic extract and fractions of Ziziphus mauritiana Lam. (Rhamnaceae) leaves from Burkina Faso
- In vitro modulation of cytochrome P450 isozymes and pharmacokinetics of caffeine by extracts of Hibiscus sabdariffa Linn calyx
- Experimental hypogonadism: insulin resistance, biochemical changes and effect of testosterone substitution
- Accelerated wound healing process in rat by probiotic Lactobacillus reuteri derived ointment
- Evaluation of inductive effects of different concentrations of cyclosporine A on MMP-1, MMP-2, MMP-3, TIMP-1, and TIMP-2 in fetal and adult human gingival fibroblasts
Articles in the same Issue
- Minireview
- Clinical assessment of arthritic knee pain by infrared thermography
- Original Articles
- Methanol stem bark extract of Adansonia digitata ameliorates chronic unpredictable mild stress-induced depression-like behavior: Involvement of the HPA axis, BDNF, and stress biomarkers pathways
- The protective effect of aqueous extract of Typha capensis rhizomes on cadmium-induced infertility in rats
- The aqueous and methanol extracts of Bambusa vulgaris (Poaceae) improve calcium and phosphorus levels, and bone microstructure in ovariectomized model of osteoporosis
- Assessment of epigenetic changes and oxidative DNA damage in rat pups exposed to polychlorinated biphenyls and the protective effect of curcumin in the prenatal period
- Assessment of heart rate variability for different somatotype category among adolescents
- Neuroprotective role of 6-Gingerol-rich fraction of Zingiber officinale (Ginger) against acrylonitrile-induced neurotoxicity in male Wistar rats
- Antioxidant activity of crude ethanolic extract and fractions of Ziziphus mauritiana Lam. (Rhamnaceae) leaves from Burkina Faso
- In vitro modulation of cytochrome P450 isozymes and pharmacokinetics of caffeine by extracts of Hibiscus sabdariffa Linn calyx
- Experimental hypogonadism: insulin resistance, biochemical changes and effect of testosterone substitution
- Accelerated wound healing process in rat by probiotic Lactobacillus reuteri derived ointment
- Evaluation of inductive effects of different concentrations of cyclosporine A on MMP-1, MMP-2, MMP-3, TIMP-1, and TIMP-2 in fetal and adult human gingival fibroblasts
