The protective effect of hydroalcoholic extract of Ginger (Zingiber officinale Rosc.) against iron-induced functional and histological damages in rat liver and kidney

Document Type : Original Research Article


1 Department of Biology, School of Sciences, Shiraz University, Shiraz, Iran

2 Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran


Objective: Iron overload in the body is related with toxic effects and threatens the health. The aim of this study was to evaluate the protective role of hydroalcoholic extract of ginger (Zingiber officinale) against ferrous sulfate-induced hepatic and renal functional disorders and histological damages in rats.
Materials and Methods: The rats were divided into four groups (n=7): Sham, Sham + G.E (ginger extract, 400 mg/kg/day for 14 days), FS (ferrous sulfate, 30 mg/kg/day for 14 days), FS+G.E (ferrous sulfate, 30 mg/kg/day for 14 days; ginger extract, 400 mg/kg/day for 11 days from the fourth day of ferrous sulfate injection). After 24 hr, blood, urine and tissue samples were collected.
Results: Compared with Sham and Sham + G.E groups, administration of ferrous sulfate resulted in liver and kidney dysfunction as evidenced by significantly higher levels of serum hepatic markers and bilirubin, and lower levels of serum albumin, total protein, triglyceride, cholesterol and glucose, as well as lower creatinine clearance and higher fractional excretion of sodium (p<0.001). This was accompanied by increased malondialdehyde levels and histological damages (p<0.001). In the FS + G.E, ginger extract significantly (p<0.01) reversed the levels of serum hepatic markers, renal functional markers and lipid peroxidation marker. Furthermore, it restored the levels of serum total protein, albumin, glucose, triglycerides and cholesterol and decreased bilirubin concentration in the blood. All these changes were corroborated by histological observations of liver and kidney.
Conclusion: In conclusion, ginger extract appears to exert protective effects against ferrous sulfate-induced hepatic and renal toxicity by reducing lipid peroxidation and chelating iron.


Main Subjects

Ajith TA, Nivitha V, Usha S. 2007. Zingiber officinale Roscoe alone and in combination with alpha-tocopherol protect the kidney against cisplatin-induced acute renal failure. Food Chem Toxicol, 45: 921-927.
Ali BH, Blunden G, Tanira MO, Nemmar A.  2008. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem Toxicol, 46:409-420.
Bhandari U, Kanojia R, Pillai KK. 2005. Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats. J Ethnopharmacol, 97:227-230
Czaja MJ. 2004. Induction and regulation of hepatocyte apoptosis by oxidative stress. Antioxid Redox Signal, 4: 759-767.
Dimitriou E, Kairis M, Sarafidou J, Michelakakis H. 2000. Iron overload and kidney alyssums. Biochemical ETBiophysical Act,1501: 138-148.
Egwurugwu JN, Ufearo CS, Abanobi OC, Nwokocha CR, Duruibe JO, Adeleye GS, Ebunlomo AO, Odetola AO, Onwufuji O. 2007. Effects of ginger (Zingiber officinale) on cadmium toxicity. Afr J Biotechnol, 6: 2078-2082.
Eton JW, Qian M. 2002. Mollecular bases of cellular iron toxicity. Free Radic Biol Med, 32: 833-840.
Hall P, Cash J. 2012. What is the real function of the liver function tests? Ulster Med J,81: 30-36.
Halliwell B, Gutteridge JM. 1990. Role of free radicals and catalytic metal ions in human disease: An overview. Methods Enzymol,186: 1-85.
Hamed MA, Ali SA, El-Rigal NS. 2012. Therapeutic potential of ginger against renal injury induced by carbon tetrachloride in rats. Sci World J Journal, 2012: 1-12.
Hampton MB, Fadeel B, Orrenius S, Ann NY. 1998. Redox regulation of the caspases during apoptosis.Acad Sci, 854: 328-335.
Harper HA, Rodwell VW, Mayes PA, Cochrum KC, Grodsky GM, Martin DWJ, Tyler DD, Wallin JD. 1979. Review of Physiological Chemistry (17th ed ed.).PP 419-492 Los Altos, California, USA Lange Medical Publications.
Jagetia G C, Baliga MS, Venkatesh P, Ulloor JN. 2003. Influence of ginger rhizome (Zingiber officinale Rosc) on survival, glutathione and lipid peroxidation in mice after whole-body exposure to gamma radiation. Radiat Res,160: 584-592.
Kadnur, SV, Goyal RK. 2005. Beneficial effects of Zingiber officinale Roscoe on fructose induced hyperipidemia and hyperinsulinemia in rats. Indian J Exp Biol,43: 1161-1164.
Kehrer JP. 2000. The Haber–Weiss reaction and mechanisms of toxicity. Toxicology,149: 43-50.
Kojima R, Randall JD, Ito E, Manshio H, Suzuki, Y, Gullans, SR. 2004 Regulation of expression of the stress response gene, Osp94 : identification of the tonicity response element and intracellular signalling pathways. Biochem,380: 783-794.
Madhusudhan K S, Oberoi R. 2011. Renal iron deposition in aplastic ane-mia: magnetic resonance imaging appearance. Indian J Nephrol , 21: 134-135.
Motawi T, Hamed M, Shabana M, Hashem R, Aboul Naser A. 2011. Zingiber officinale acts as a nutraceutical agent against liver fibrosis. Nutr and Metabolis, 8: 1-11.
Oboh G, Akinyemi AJ, Ademiluyi AO. 2012. Antioxidant and inhibitory effect of red ginger (Zingiber officinale var. Rubra) and white ginger (Zingiber officinale Roscoe) on Fe (2+) induced lipid peroxidation in rat brain in vitro. Exp Toxicol Pathol, 64: 31-36.
Papanastasiou, DA, Vayenas, DV, Vassilopoulos A, Repanti M. 2000. Concentration of iron and distribution of iron and transferrin afterexperimental iron overload in rat tissues in vivo: study of the liver,the spleen, the central nervous system and other organs. Pathol ResPract,1: 47-54.
Pari L, Asaithambi K, Paramasivam K, Ayyasamy R. 2015. Protective effects of hesperidin on oxidative stress, dyslipidaemia and histological changes in iron-induced hepatic and renal toxicity in rats. Toxicol Rep, 2: 46-55.
Pawa, N, Nimbalkar V, Gaikvad P. 2012. Hepatoprotective activity of a polyherbal mixture in ferrous sulphate and ethanol induced hepatotoxicity experimental animals. Der Pharmacia Sinica, 3: 594-597.
Poorrostami A, Farokhi F, Heidari R. 2014. Effect of hydroalcoholic extract of ginger on the liver of epileptic female rats treated with lamotrigine. Avicenna J Phytomed, 4: 276-286.
Powell LW, Basset, M L, Halliday, JW. 1980. Hemochromatosis: 1980 update. Gastroenterology, 78: 374-381.
Rhodes R S, DePalma, RG. (1980. Mitochondrial dysfunction of the liver and hypoglycemia in hemorrhagic shock. Surg Gynecol Obstet, 150: 347-352.
Rodrigues FA, Prata, MM, Oliveira IC, Alves NT, Freitas RE, Monteiro HS. Silva, JA, Vieira PC,Viana DA, Liborio AB, Havt A. 2014. Gingerol fraction from Zingiber officinale protects against gentamicin-induced nephrotoxicity. Antimicrob Agents Chemother, 58: 1872-1878.
Sarkar R, Hazra B, Mnndal N. 2013. Anti-oxidative protection against iron overload-induced liver damage in mice by cajanus cajan (L.) Millsp. Leaf extract. Indian J Exp Biol., 15: 165-173.
Selvi RS. 2012. Hepatoprotective effect of Camellia sinesis L. against Ferrous Sulphate induced Toxicity in Swiss Albino Rats.  Int J Med Biosci , 1: 49-54.
Thomson M, Al-Qattan KK, Al-Sawan SM, Alnaqeeb MA, Khan I, Ali M. 2002. The use of ginger (Zingiber officinale Rosc.) as a potential anti-inflammatory and antithrombotic agent. Prostaglandins Leukot. Essent. Fatty Acids,67: 475-478.
Videla L A, Fernandez V, Tapia G, Varela P. 2003. Oxidative stress mediated hepatotoxicity of iron and copper: role of Kupffer cells. Biometals, 16: 103-111.
Vishwakarma SL, Pal, SC, Kasture VS, Kasture, SB. 2002. Anxiolytic and antiemetic activity of Zingiber officinale. Phytother Res,16: 621-626.
Zager, RA, Johnson, ACM, Hanson SY. 2004. Parenteral iron nephrotoxicity: Potential mechanisms and consequences. Kidney Int, 66:144-156.