Similar articles

Abstract: paracetamol (PCM) overdose can cause nephrotoxicity with oxidative stress as one of the possible mechanisms mediating the event. In this study, the effects of ethyl acetate extract of Zingiber zerumbet rhizome [200 mg per kg of body weight (mg/kg) and 400 mg/kg] on PCM-induced nephrotoxicity were examined. Rats were divided into five groups containing 10 rats each. The control group received distilled water while other groups were treated with extract alone (400 mg/kg), PCM alone (750 mg/kg), 750 mg/kg PCM+200 mg/kg extract (PCM+200-extract), and 750 mg/kg PCM+400 mg/kg extract (PCM+400-extract), respectively, for seven consecutive days. The Z. zerumbet extract was given intraperitoneally concurrent with oral administration of PCM. Treatment with Z. zerumbet extract at doses of 200 and 400 mg/kg prevented the PCM-induced nephrotoxicity and oxidative impairments of the kidney, as evidenced by a significantly reduced (P<0.05) level of plasma creatinine, plasma and renal malondialdehyde (MDA), plasma protein carbonyl, and renal advanced oxidation protein product (AOPP). Furthermore, both doses were also able to induce a significant increment (P<0.05) of plasma and renal levels of glutathione (GSH) and plasma superoxide dismutase (SOD) activity. The nephroprotective effects of Z. zerumbet extract were confirmed by a reduced intensity of renal cellular damage, as evidenced by histological findings. Moreover, Z. zerumbet extract administered at 400 mg/kg was found to show greater protective effects than that at 200 mg/kg. In conclusion, ethyl acetate extract of Z. zerumbet rhizome has a protective role against PCM-induced nephrotoxicity and the process is probably mediated through its antioxidant properties.

[1]Abdel-Zaher, A.O., Abdel-Rahman, M.M., Hafez, M.M., Omran, F.M., 2007. Role of nitric oxide and reduced glutathione in the protective effects of aminoguanidine, gadolinium chloride and oleanolic acid against acetaminophen-induced hepatic and renal damage. Toxicology, 234(1-2):124-134.

[2]Abdul, A.B., Abdelwahab, S.I., Al-Zubairi, A.S., Elhassan, M.M., Murali, S.M., 2008. Anticancer and antimicrobial activities of zerumbone from the rhizomes of Zingiber zerumbet. Int. J. Pharmacol., 4(4):301-304.

[3]Alderman, C.J., Shah, S., Foreman, J.C., Chain, B.M., Katz, D.R., 2002. The role of advanced oxidation protein products in regulation of dendritic cell function. Free Radic. Biol. Med., 32(5):377-385.

[4]Beyer, W., Fridovich, I., 1987. Assaying for superoxide dismutase activity: some large consequences of minor changes in conditions. Anal. Biochem., 161(2):559-566.

[5]Blakely, P., McDonald, B.R., 1995. Acute renal failure due to acetaminophen ingestion: a case report and review of the literature. J. Am. Soc. Nephrol., 6(1):48-53.

[6]Borne, R.F., 1995. Nonsteroidal Anti-Inflammatory Drugs. In: Foye, W.O., Lemke, T.L., Williams, D.A. (Eds.), Principles of Medicinal Chemistry. Williams & Wilkins, p.535-580.

[7]Boutis, K., Shannon, M., 2001. Nephrotoxicity after acute severe acetaminophen poisoning in adolescents. Clin. Toxicol., 39(5):441-445.

[8]Brown, R.A., 1968. Hepatic and renal damage with paracetamol overdosage. J. Clin. Pathol., 21(6):793.

[9]Carpenter, H.M., Mudge, G.H., 1981. Acetaminophen nephrotoxicity: studies on renal acetylation and deacetylation. J. Pharmacol. Exp. Ther., 218(1):161-167.

[10]Chevion, M., Berenshtein, E., Stadtman, E.R., 2000. Human studies related to protein oxidation: protein carbonyl content as a marker of damage. Free Radic. Res., 11(33):S99-S108.

[11]Das, J., Ghosh, J., Manna, P., Sil, P.C., 2010. Taurine protects acetaminophen-induced oxidative damage in mice kidney through APAP urinary excretion and CYP2E1 inactivation. Toxicology, 269(1):24-34.

[12]Dilger, R.N, Baker, D.H., 2007. Oral N-acetyl-L-cysteine is a safe and effective precursor of cysteine. J. Anim. Sci., 85(7):1712-1718.

[13]Ellman, G.L., 1959. Tissue sulphydryl groups. Arch. Biochem., 82(1):70-77.

[14]Esterbauer, H., Cheeseman, K.H., 1990. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Meth. Enzymol., 186:407-421.

[15]Gunnell, D., Murray, V., Hawton, K., 2000. Use of paracetamol (acetaminophen) for suicide and nonfatal poisoning: worldwide patterns of use and misuse. Suicide Life Threat. Behav., 30(4):313-326.

[16]Hart, S.G., Beierschmitt, W.P., Wyand, D.S., Khairallah, E.A., Cohen, S.D., 1994. Acetaminophen nephrotoxicity in CD-1 mice. I. Evidence of a role for in situ activation in selective covalent binding and toxicity. Toxicol. Appl. Pharmacol., 126(2):267-275.

[17]Hemabarathy, B., Budin, S.B., Feizal, V., 2009. Paracetamol hepatoxicity in rats treated with crude extract of Alpinia galanga. J. Biol. Sci., 9(1):57-62.

[18]Huang, G.C., Chien, T.Y., Chen, L.G., Wang, C.C., 2005. Antitumor effects of zerumbone from Zingiber zerumbet in P-388D1 cells in vitro and in vivo. Planta Med., 71(3):219-224.

[19]Ibrahim, M.Y., Abdul, A.B., Ibrahim, T.A., AbdelWahab, S.I., Elhassan, M.M., Mohan, S., 2010. Attenuation of cisplatin-induced nephrotoxicity in rats using zerumbone. Afr. J. Biotechnol., 9(28):4434-4441.

[20]Jaganath, I.B., Ng, L.T., 2000. Herbs: The Green Pharmacy of Malaysia. Vinpress Sdn. Bhd, Malaysia, p.95-99.

[21]Kaderi, M.G., Habib, M.R., Nikkon, F., Yeasmin, T., Rashid, M.A., Rahman, M.M., Gibbons, S., 2010. Zederone from the rhizomes of Zingiber zerumbet and its antistaphylococcal activity. Latin Am. Caribbean Bull. Med. Arom. Plants, 9(1):63-68 (in Spanish).

[22]Kaplowitz, N., 2000. Mechanism of liver cell injury. J. Hepatol., 32(S1):39-47.

[23]Kheradpezhouh, E., Panjehshahin, M.R., Miri, R., Javidnia, K., Noorafshan, A., Monabati, A., Dehpour, A.R., 2010. Curcumin protects rats against acetaminophen-induced hepatorenal damages and shows synergistic activity with N-acetyl cysteine. Eur. J. Pharmacol., 628(1-3):274-281.

[24]Levine, R.L., Williams, J., Stadtman, E.R., Shacter, E., 1990. Carbonyl assays for determination of oxidatively modified proteins. Meth. Enzymol., 233:346-357.

[25]Margetis, P.I., Antonelou, M.H., Petropoulos, I.K., Margaritis, L.H., Papassideri, I.S., 2009. Increased protein carbonylation of red blood cell membrane in diabetic retinopathy. Exp. Mol. Pathol., 87(1):76-82.

[26]McMurtry, R.J., Snodgrass, W.R., Mitchell, J.R., 1978. Renal necrosis, glutathione depletion, and covalent binding after acetaminophen. Toxicol. Appl. Pharmacol., 46(1):87-100.

[27]Mitchell, J.R., McMurtry, R.J., Statham, C.N., Nelson, S.D., 1977. Molecular basis for several drug-induced nephropathies. Am. J. Med., 62(4):518-526.

[28]Nakamura, Y., Yoshida, C., Murakami, A., Ohigashi, H., Osawa, T., Uchida, K., 2004. Zerumbone, a tropical ginger sesquiterpene, activates phase II drug metabolizing enzymes. FEBS Lett., 572(1-3):245-250.

[29]Nelson, S.D., 1995. Mechanisms of the formation and disposition of reactive metabolites that can cause acute liver injury. Drug Metab. Rev., 27(1-2):147-177.

[30]Newton, J.F., Yoshimoto, M., Bernstein, J., Rush, G.F., Hook, J.B., 1983. Acetaminophen nephrotoxicity in the rat. 1. Strain differences in nephrotoxicity and metabolism. Toxicol. Appl. Pharmacol., 69(2):291-306.

[31]Pietta, P.G., 2000. Flavonoids as antioxidants. J. Nat. Prod., 63(7):1035-1042.

[32]Placke, M.E., Wyand, D.S., Cohen, S.D., 1987. Extrahepatic lesions induced by acetaminophen in the mouse. Toxicol. Pathol., 15(4):381-387.

[33]Rashid, R.A., Hawariah, A., Pihie, L., 2005. The antiproliferative effects of Zingiber zerumbet extracts and fractions on the growth of human breast carcinoma cell lines. Malays. J. Pharma. Sci., 3(1):45-52.

[34]Ruslay, S., Abas, F., Shaari, K., Zainal, Z., Maulidiani, Sirat, H., Israf, D.A., Lajis, N.H., 2007. Characterization of the components present in the active fractions of health gingers (Curcuma xanthorrhiza and Zingiber zerumbet) by HPLC-DAD-ESIMS. Food Chem., 104(3):1183-1191.

[35]Saadiah, M.S., Halijah, I., 1995. Zingiberaceae. Proceedings of the National Convention on Herbal Medicine. Forest Research Institute Malaysia, Kuala Lumpur, p.205-207.

[36]Sharifah Sakinah, S.A., Handayani, S.T., Azimahtol, L.P., 2007. Zerumbone induced apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio. Cancer Cell Inter., 7(1):4.

[37]Slot, C., 1965. Plasma creatinine determination. A new & specific Jaffe reaction method. Scand. J. Clin. Lab. Invest., 17(4):381-387.

[38]Somchit, M.N., Shukriyah, M.H., 2003. Anti-inflammatory property of ethanol and water extracts of Zingiber zerumbet. Ind. J. Pharmacol., 35:181-182.

[39]Witko-Sarsat, V., Friedlander, M., Capeillere-Blandin, C., Nguyen-Khoa, T., Nguyen, A.T., Zingraff, J., Jungers, A.T., Descamps-Latscha, B., 1996. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int., 49(5):1304-1313.

[40]Yousef, M.I., Omar, S.A., El-Guendi, M.I., Abdelmegid, L.A., 2010. Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, liver and kidney functions and haematotoxicity in rat. Food Chem. Toxicol., 48(11):3246-3261.