• SARA DERBAL Department of Biology, Laboratory of Animal Ecophysiology, Faculty of Sciences, Badji Mokhtar University, Annaba, Algeria.
  • ZINE KECHRID Department of Biochemistry, Laboratory of Applied Biochemistry and Microbiology, Faculty of Sciences, Badji Mokhtar University, Annaba, Algeria.


Objective: This study was performed to study the potential capacity effect of ginger on the modulation effects of nickel-induced hepatotoxicity.

Methods: Thirty-two female albino Wistar rats were divided into four groups of eight each. One served as a control group, the second group (Gi) received ginger 20 g/kg diet, while the third group (Ni) was given nickel 800 mg/L in their drinking water as NiSO46H2O and the fourth group (Ni+Gi) was treated daily with both nickel and ginger. The experiment was lasted for 21 days.

Results: The exposure to nickel led to a significant decrease in body weight and food intake with an increase of liver weight. Nickel treatment also produced oxidative liver injury characterized by an increase of glucose, cholesterol, triglyceride, total lipids, bilirubin, malondialdehyde (MDA) concentrations and glutamate-pyruvate transaminase, glutamic oxaloacetic transaminase, and alkaline phosphatase activities. Meanwhile, serum total proteins and liver reduced glutathione (GSH) levels, catalase, GSH peroxidase, and GSH superoxide dismutase activities were decreased. These results are substantiated with marked changes in the histopathology, whereas the supplementation of ginger resulted in a restoration of the previous parameters.

Conclusion: It seems that ginger supplementation is a potent factor for reducing the oxidative severity of nickel hepatotoxicity through its antioxidant action.

Keywords: Nickel, Ginger, Glutathione, Liver, Hepatotoxicity, Rat

Author Biography

ZINE KECHRID, Department of Biochemistry, Laboratory of Applied Biochemistry and Microbiology, Faculty of Sciences, Badji Mokhtar University, Annaba, Algeria.

Dr. Zine Kechrid, Department of Biochemistry, University of Annaba, Annaba, Algeria


1. Maity S, Roy S, Chaudhury S, Bhattacharya S. Antioxidant responses of the earthworm Lampito mauritii exposed to Pb and Zn contaminated soil. Environ Pollut 2008;151:1-7.
2. Sengupta P. Environmental and occupational exposure of metals and their role in male reproductive functions. Drug Chem Toxicol2013;36:353-68.
3. Cempel M, Nikel G. Nickel: A review of its sources and environmental toxicology. Pol J Environ Stud 2006;15:375-82.
4. Environmental Protection Agency United States. Health Assessment Document for Nickel. National Service Center for Environmental Assessment, Office of Research and Development. Washington DC: Environmental Protection Agency United States; 1985.
5. Buekers J, De Brouwere K, Lefebvre W, Willems H, Vandenbroele M, Van Sprang P, et al. Assessment of human exposure to environmental sources of nickel in Europe: Inhalation exposure. Sci Total Environ 2015;521-522:359-71.
6. Onkelinx C, Becker J, Sunderman FW Jr. Compartmental analysis of the metabolism of 63Ni(II) in rats and rabbits. Res Commun Chem Pathol Pharmacol 1973;6:663-76.
7. El-Bakry HA, El-Sherif G, Rostom RM. Therapeutic dose of green tea extract provokes liver damage and exacerbates paracetamol-induced hepatotoxicity in rats through oxidative stress and caspase 3-dependent apoptosis. Biomed Pharmacother 2017;96:798-811.
8. Adjroud O. The toxic effects of nickel chloride on liver, erythropoiesis, and development in wistar albino preimplanted rats can be reversed with selenium pretreatment. Environ Toxicol 2013;28:290-8.
9. Wang Y, Wang SY, Jia L, Zhang L, Ba JC, Han D, et al. Nickel-refining fumes induced DNA damage and apoptosis of NIH/3T3 cells via oxidative stress. Int J Environ Res Public Health 2016;13:629.
10. Vijayavel K, Gopalakrishnan S, Thiagarajan R, Thilagam H. Immunotoxic effects of nickel in the mud crab Scylla serrata. Fish Shellfish Immunol 2009;26:133-9.
11. Laylani LA. Effect of Carthamus tinctorius safflower aqueous extract against nickel chloride induces hematotoxicity and immunotoxicity in adult male rabbits. Ibn Al Haitham J Pure Appl Sci 2017;30:19-26.
12. Song X, Kenston SS, Kong L, Zhao J. Molecular mechanisms of nickel induced neurotoxicity and chemoprevention. Toxicology 2017;392:47 54.
13. Sun H, Wu W, Guo J, Xiao R, Jiang F, Zheng L, et al. Effects of nickel exposure on testicular function, oxidative stress, and male reproductive dysfunction in Spodoptera litura Fabricius. Chemosphere 2016;148:178-87.
14. Phillips JI, Green FY, Davies JC, Murray J. Pulmonary and systemic toxicity following exposure to nickel nanoparticles. Am J Ind Med 2010;53:763-7.
15. Bouhalit S, Kechrid Z. Protective role of L-cysteine against nickel induced hepatotoxicity in Albino Wistar rats. J Pharmacol Med Chem 2018;2:32-5.
16. Bouhalit S, Kechrid Z, EL-Feki A. Effect of silymarin extracted from Silybum marlanum on nickel hematotoxicity and nephrotoxicity in male albino Wistar rats. Int J Pharm Pharm Sci 2017;9:84-9.
17. Elangovan P, Amudha K, Shagirtha K. Naringin improves nickel-induced alterations of acetylcholinesterase, adenosine triphosphatases, and oxidative stress in brain of rats. J Nat Prod Biom Res 2015;1:21-8.
18. Anilakumar KR, Saritha V, Khanum F, Bawa AS. Ameliorative effect of ajwain extract on hexachlorocyclohexane-induced lipid peroxidation in rat liver. Food Chem Toxicol 2009;47:279-82.
19. Ahmad B, Rehman MU, Amin I, Arif A, Rasool S, Bhat SA, et al. A review on pharmacological properties of zingerone (4-(4-hydroxy-3-methoxyphenyl)-2-butanone). ScientificWorldJournal 2015;2015:816364.
20. Tao Y, Li W, Liang W, Van Breemen RB. Identification and quantification of gingerols and related compounds in ginger dietary supplements using high-performance liquid chromatography-tandem mass spectrometry. J Agric Food Chem 2009;57:10014-21.
21. Ali BH, Blunden G, Tanira MO, Nemmar A. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale roscoe): A review of recent research. Food Chem Toxicol 2008;46:409-20.
22. Jeena K, Liju VB, Kuttan R. Antioxidant, anti-inflammatory and antinociceptive activities of essential oil from ginger. Indian J Physiol Pharmacol 2013;57:51-62.
23. Khan AM, Shahzad M, Asim MB, Imran M, Shabbir A. Zingiber officinale ameliorates allergic asthma via suppression of th2-mediated immune response. Pharm Biol 2015;53:359-67.
24. Lete I, Allué J. The effectiveness of ginger in the prevention of nausea and vomiting during pregnancy and chemotherapy. Integr Med Insights 2016;11:11-7.
25. Murad S, Niaz K, Aslam H. Effects of ginger on LDL-C, total cholesterol and body weight. Clin Med Biochem 2018;4:1-3.
26. Nanjundaiah SM, Annaiah HN, Dharmesh SM. Gastroprotective effect of ginger rhizome (Zingiber officinale) extract: Role of gallic acid and cinnamic acid in H(+), K(+)-ATPase/H. pylori inhibition and anti-oxidative mechanism. Evid Based Complement Alternat Med 2011;2011:249487.
27. Chang JS, Wang KC, Yeh CF, Shieh DE, Chiang LC. Fresh ginger (Zingiber officinale) has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines. J Ethnopharmacol 2013;145:146-51.
28. Al-Amin ZM, Thomson M, Al-Qattan KK, Peltonen-Shalaby R, Ali M. Anti-diabetic and hypolipidaemic properties of ginger (Zingiber officinale) in streptozotocin-induced diabetic rats. Br J Nutr 2006;96:660-6.
29. Sidhu P, Garg ML, Dhawan DK. Protective role of zinc in nickel induced hepatotoxicity in rats. Chem Biol Interact 2004;150:199-209.
30. Krim M, Messaadia A, Maidi I, Aouacheri O, Saka S. Protective effect of ginger against toxicity induced by chromate in rats. Ann Biol Clin (Paris) 2013;71:165-73.
31. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1984;105:302-10.
32. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70-7.
33. 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;11:151-69.
34. Flohé L, Günzler WA. Assays of glutathione peroxidase. Methods Enzymol 1984;105:114-21.
35. Aebi H. Catalase in vitro. Methods Enzymol 1984;105:121-6.
36. Misra HP, Fridovich I. Superoxide dismutase: “Positive” spectrophotometric assays. Anal Biochem 1977;79:553-60.
37. Bradford MM. A 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.
38. Hould R. Techniques d’histopathologie et de Cytopathologie. Paris: Editions Maloine; 1984.
39. Layachi N, Kechrid Z. Combined protective effect of Vitamins C and E on cadmium induced oxidative liver injury in rats. Afr J Biot 2012;11:16013-20.
40. Gueroui M, Kechrid Z. Evaluation of some biochemical parameters and brain oxidative stress in experimental rats exposed chronically to silver nitrate and the protective role of vitamin E and selenium. Toxicol Res 2016;32:301-9.
41. Djemli S, Kechrid Z. Preventive effect of zinc on nickel-induced oxidative liver injury in rats. Afr J Biot 2013;12:7112-19.
42. Dahdouh F, Attalah S, Djabar MR, Kechrid Z. Effect of the joint supplementation of Vitamin C and Vitamin E on nickel heamatotoxicity and nephrotoxicity in male Swiss albino mice. Int J Pharm Pharm Sci 2016;8:234-9.
43. Hamdiken M, Kechrid Z. Chard (Beta vulgaris Var. Cilca) extract modulates status, glucose level and antioxidant values in diabetic rats fed zinc deficiency diet. Int J Pharm Pharm Sci 2017;9:297-304.
44. Egwurugwu JN, Ufearo CS, Abanobi OC, Nwokocha CR, Duruibe JO, Adeleye GS, et al. Effects of ginger (Zingiber officinale) on cadmium toxicity. Afr J Biot 2007;6:2078-82.
45. Sharma S, Singhgill A. Restorative effects of Zingber officinale on arsenic-induced genottoxic effects in chromosomal structure of mice. Asian J Pharm Clin Res 2018;11:471-5.
46. Dormer RL, Kerbey AL, McPherson M, Manley S, Ashcroft SJ, Schofield JG, et al. The effect of nickel on secretory systems. Studies on the release of amylase, insulin and growth hormone. Biochem J 1974;140:135-42.
47. Cartañà J, Arola L. Nickel-induced hyperglycaemia: The role of insulin and glucagon. Toxicology 1992;71:181-92.
48. Akash MS, Rehman K, Tariq M, Chen S. Zingiber officinale and Type 2 diabetes mellitus: Evidence from experimental studies. Crit Rev Eukaryot Gene Expr 2015;25:91-112.
49. Li Y, Tran VH, Duke CC, Roufogalis BD. Gingerols of Zingiber officinale enhance glucose uptake by increasing cell surface GLUT4 in cultured L6 myotubes. Planta Med 2012;78:1549-55.
50. Rani MP, Padmakumari KP, Sankarikutty B, Cherian OL, Nisha VM, Raghu KG, et al. Inhibitory potential of ginger extracts against enzymes linked to Type 2 diabetes, inflammation and induced oxidative stress. Int J Food Sci Nutr 2011;62:106-10.
51. Tikare SN, Yendigeri S, Das Gupta A, Dhundasi SA, Das KK. Protective effect of ?-tocopherol against hematotoxicity, hepatotoxicity and nephrotoxicity induced by nickel sulfate in male albino rats. Indian J Physiol Pharmacol 2013;57:280-92.
52. Sabiu S, Sunmonu TO, Ajani EO, Ajiboye TO. Combined administration of silymarin and Viamin C stalls acetaminophen-mediated hepatic oxidative insults in Wistar rats. Rev Bras Farmacogn 2015;25:9-34.
53. Chinoy NJ, Memon MR. Beneficial effects of some vitamins and calcium on fluoride and aluminium toxicity on gastrocnemius muscle and liver of male mice. Fluoride 2001;34:21-33.
54. Ajith TA, Nivitha V, Usha S. Zingiber officinale roscoe alone and in combination with alpha-tocopherol protect the kidney against cisplatin-induced acute renal failure. Food Chem Toxicol 2007;45:921-7.
55. Misra M, Rodriguez RE, Kasprzak KS. Nickel induced lipid peroxidation in the rat: Correlation with nickel effect on antioxidant defense systems. Toxicology 1990;64:1-7.
56. Rems L, Viano M, Kasimova MA, Miklav?i? D, Tarek M. The contribution of lipid peroxidation to membrane permeability in electropermeabilization: A molecular dynamics study. Bioelectrochemistry 2019;125:46-57.
57. Chen CY, Wang YF, Lin YH, Yen SF. Nickel-induced oxidative stress and effect of antioxidants in human lymphocytes. Arch Toxicol 2003;77:123-30.
58. Boulila S, Elfeki A, Oudadesse H, Elfeki H. Substitution effects of a carbonated hydroxyapatite biomaterial against intoxication chloride nickel-exposed rats. Toxicol Mech Methods 2015;25:155-65.
59. Hfaiedh N, Allagui MS, Hfaiedh M, Feki AE, Zourgui L, Croute F, et al. Protective effect of cactus (Opuntiac ficus indica) cladode extract upon nickel-induced toxicity in rats. Food Chem Toxicol 2008;46:3759-63.
60. Ihechiluru NB, Henry AN, Taiwo IE. Heavy metal bioaccumulation and oxidative stress in austroaeschnainermis (dragon fly) of the Lagos urban ecosystem. J Environ Chem Ecotoxicol 2015;7:11-19.
61. Reham ZH, Mohammad SA. Amelioration of paracetamol hepatotoxicity and oxidative stress on mice liver with silymarin and extract supplements. Asian Pac J Trop Biomed 2015;5:521-31.
62. Reddy YA, Chalamaiah M, Ramesh B, Balaji G, Indira P. Ameliorating activity of ginger (Zingiber officinale) extract against lead induced renal toxicity in male rats. J Food Sci Technol 2014;51:908-14.
63. Khattab HA, Al-Amoudi NS, Al-Faleh, AA. Effect of ginger, curcumin and their mixture on blood glucose and lipids in diabetic Rats. Life Sci J 2013;10:428-42.
64. Shobana S, Naidu KA. Antioxidant activity of selected Indian spices. Prostaglandins Leukot Essent Fatty Acids 2000;62:107-10.
281 Views | 110 Downloads
How to Cite
SARA DERBAL, and ZINE KECHRID. “THE BENEFIT EFFECT OF GINGER SUPPLEMENTATION AGAINST NICKEL-INDUCED HEPATOTOXICITY IN ALBINO WISTAR RATS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 9, July 2019, pp. 178-83, doi:10.22159/ajpcr.2019.v12i9.34393.
Original Article(s)