Hepatoprotective effect of curcumin and alpha-tocopherol against cisplatin-induced oxidative stress

BMC Complementary and Alternative Medicine

Prasit Suwannalert¹  Phanit Koomhin²  Chuchard Punsawad²  Sarawoot Palipoch² 

[1] Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand;School of Medicine, Walailak University, Nakhon Si Thammarat 80161, Thailand

关键词: Hepatotoxicity;    α-Tocopherol;    Curcumin;    Oxidative stress;    Cisplatin;   

Others  :  1220212
DOI  :  10.1186/1472-6882-14-111

 received in 2013-11-12, accepted in 2014-03-24,  发布年份 2014

【 摘 要 】

Background

cis-Diammineplatinum (II) dichloride (cisplatin) is the important anti-cancer agent useful in treatment of various cancers. Unfortunately, it can produce unwanted side effects in various tissues, including the liver. The present study investigated the possible protective role of curcumin and α-tocopherol against oxidative stress-induced hepatotoxicity in rats upon cisplatin treatment.

Methods

Male Wistar rats were divided into five groups (n = 5). Saline and Cis groups, rats were intraperitoneal (i.p.) injected with normal saline and cisplatin [20 mg/kg body weight (b.w.)], respectively. Cis + α-tocopherol group, Cis + Cur group and Cis + α-tocopherol + Cur group, rats were pre-treated with a single dose of α-tocopherol (250 mg/kg b.w.), curcumin (200 mg/kg b.w.) and combined α-tocopherol with curcumin, respectively, for 24 h prior the administration of cisplatin. After 72 h of first injection, specimens were collected. Liver enzyme, lipid peroxidation biomarker, liver histopathology and gene expression of liver nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were investigated.

Results

Cisplatin revealed a significant increase of hepatic malondialdehyde (MDA) levels and a significant reduction of hepatic superoxide dismutase (SOD) and catalase activities compared to the saline group. It elicited a marked increase of the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and demonstrated the liver pathologies including liver congestion, disorganization of hepatic cords and ground glass appearance of hepatocytes. It also demonstrated a significant increase of NADPH oxidase gene expression compared to saline group. Pre-treatment with combined curcumin and α-tocopherol improved the liver enzymes, lipid peroxidation biomarker, liver histopathology and gene expression of liver NADPH oxidase in cisplatin-treated rats.

Conclusions

The findings indicate that pre-treatment with combined curcumin and α-tocopherol can protect cisplatin-induced hepatotoxicity including the biochemical, histological and molecular aspects. The down-regulations of NADPH oxidase gene expression may be involved in abrogating oxidative stress via reduction of reactive oxygen species (ROS) production.

【 授权许可】

   
2014 Palipoch et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 2.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Rabik CA, Dolan ME: Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev 2007, 33:9-23.
• [2]Liao Y, Lu X, Lu C, Li G, Jin Y, Tang H: Selection of agents for prevention of cisplatin-induced hepatotoxicity. Pharmacol Res 2008, 57(2):125-131.
• [3]Palipoch S, Punsawad C: Biochemical and histological study of rat liver and kidney injury induced by Cisplatin. J Toxicol Pathol 2013, 26(3):293-299.
• [4]Arany I, Safirstein RL: Cisplatin nephrotoxicity. Semin Nephrol 2003, 23:460-464.
• [5]Robbins MEC, Zhao W, Davis CS, Toyokuni S, Bonsib SM: Radiation-induced kidney injury: a role for chronic oxidative stress? Micron 2002, 33(2):133-141.
• [6]MacNee W: Oxidative stress and lung inflammation in airways disease. Eur J Pharmacol 2001, 429(1–3):195-207.
• [7]Palipoch S: A review of oxidative stress in acute kidney injury: protective role of medicinal plants-derived antioxidants. Afr J Tradit Complement Altern Med 2013, 10:88-93.
• [8]Babior BM: NADPH oxidase. Curr Opin Immunol 2004, 16:42-47.
• [9]Pan X, Dai Y, Li X, Niu N, Li W, Liu F, Zhao Y, Yu Z: Inhibition of arsenic induced-rat liver injury by grape seed exact through suppression of NADPH oxidase and TGF-β/Smad activation. Toxicol Appl Pharmacol 2011, 254(3):323-331.
• [10]Fujimori N, Oono T, Igarashi H, Ito T, Nakamura T, Uchida M, Coy DH, Jensen RT, Takayanagi R: Vasoactive intestinal peptide reduces oxidative stress in pancreatic acinar cells through the inhibition of NADPH oxidase. Peptides 2011, 32(10):2067-2076.
• [11]Muller FL, Song W, Liu Y, Chaudhuri A, Pieke-Dahl S, Strong R, Huang T-T, Epstein CJ, Roberts LJ 2nd, Csete M, Faulkner JA, Van Remmen H: Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy. Free Radic Biol Med 2006, 40(11):1993-2004.
• [12]Kessova IG, Ho Y-S, Thung S, Cederbaum AI: Alcohol-induced liver injury in mice lacking Cu, Zn-superoxide dismutase. Hepatology 2003, 38(5):1136-1145.
• [13]Kim SJ, Lee JW, Jung YS, Kwon DY, Park HK, Ryu CS, Kim SK, Oh GT, Kim YC: Ethanol-induced liver injury and changes in sulfur amino acid metabolomics in glutathione peroxidase and catalase double knockout mice. J Hepatol 2009, 50(6):1184-1191.
• [14]M. Khopde S, Priyadarsini KI, Venkatesan P, Rao MNA: Free radical scavenging ability and antioxidant efficiency of curcumin and its substituted analogue. Biophys Chem 1999, 80(2):85-91.
• [15]Gao S, Duan X, Wang X, Dong D, Liu D, Li X, Sun G, Li B: Curcumin attenuates arsenic-induced hepatic injuries and oxidative stress in experimental mice through activation of Nrf2 pathway, promotion of arsenic methylation and urinary excretion. Food Chem Toxicol 2013, 59:739-747.
• [16]Palipoch S, Punsawad C, Chinnapun C, Suwannalert P: Amelioration of cisplatin-induced nephrotoxicity in rats by curcumin and α-tocopherol. Trop J Pharm Res 2013, 12(6):973-979.
• [17]Rashed LA, Hashem RM, Soliman HM: Oxytocin inhibits NADPH oxidase and P38 MAPK in cisplatin-induced nephrotoxicity. Biomed Pharmacother 2011, 65:474-480.
• [18]Horton AA, Fairhurst S: Lipid peroxidation and mechanisms of toxicity. Crit Rev Toxicol 1987, 18(1):27-79.
• [19]Etsuo N: Lipid peroxidation: Physiological levels and dual biological effects. Free Radic Biol Med 2009, 47(5):469-484.
• [20]Kart A, Cigremis Y, Karaman M, Ozen H: Caffeic acid phenethyl ester (CAPE) ameliorates cisplatin-induced hepatotoxicity in rabbit. Exp Toxicol Pathol 2010, 62(1):45-52.
• [21]Hassan I, Chibber S, Naseem I: Ameliorative effect of riboflavin on the cisplatin induced nephrotoxicity and hepatotoxicity under photoillumination. Food Chem Toxicol 2010, 48(8–9):2052-2058.
• [22]Molina-Jijón E, Tapia E, Zazueta C, El Hafidi M, Zatarain-Barrón ZL, Hernández-Pando R, Medina-Campos ON, Zarco-Márquez G, Torres I, Pedraza-Chaverri J: Curcumin prevents Cr(VI)-induced renal oxidant damage by a mitochondrial pathway. Free Radic Biol Med 2011, 51(8):1543-1557.
• [23]Aggarwal BB, Harikumar KB: Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 2009, 41(1):40-59.
• [24]Maheshwari RK, Singh AK, Gaddipati J, Srimal RC: Multiple biological activities of curcumin: a short review. Life Sci 2006, 78(18):2081-2087.
• [25]Ak T, Gülçin İ: Antioxidant and radical scavenging properties of curcumin. Chem Biol Interact 2008, 174(1):27-37.
• [26]Galano A, Álvarez-Diduk R, Ramírez-Silva MT, Alarcón-Ángeles G, Rojas-Hernández A: Role of the reacting free radicals on the antioxidant mechanism of curcumin. Chem Phys 2009, 363(1–3):13-23.
• [27]Jayaprakasha GK, Jaganmohan Rao L, Sakariah KK: Antioxidant activities of curcumin, demethoxycurcumin and bisdemethoxycurcumin. Food Chem 2006, 98(4):720-724.
• [28]Naik SR, Thakare VN, Patil SR: Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: Evidence of its antioxidant property. Exp Toxicol Pathol 2011, 63(5):419-431.
• [29]Eybl V, Kotyzova D, Koutensky J: Comparative study of natural antioxidants – curcumin, resveratrol and melatonin - in cadmium-induced oxidative damage in mice. Toxicology 2006, 225(2–3):150-156.
• [30]Banudevi S, Krishnamoorthy G, Venkataraman P, Vignesh C, Aruldhas MM, Arunakaran J: Role of α-tocopherol on antioxidant status in liver, lung and kidney of PCB exposed male albino rats. Food Chem Toxicol 2006, 44(12):2040-2046.
• [31]Sodhi S, Sharma A, Brar APS, Brar RS: Effect of α tocopherol and selenium on antioxidant status, lipid peroxidation and hepatopathy induced by malathion in chicks. Pestic Biochem Phys 2008, 90(2):82-86.
• [32]Khalil OAK, de Faria Oliveira OMM, Vellosa JCR, de Quadros AU, Dalposso LM, Karam TK, Mainardes RM, Khalil NM: Curcumin antifungal and antioxidant activities are increased in the presence of ascorbic acid. Food Chem 2012, 133(3):1001-1005.
• [33]Subudhi U, Chainy GBN: Expression of hepatic antioxidant genes in l-thyroxine-induced hyperthyroid rats: Regulation by vitamin E and curcumin. Chem Biol Interact 2010, 183(2):304-316.
• [34]Huang X, Sun M, Li D, Liu J, Guo H, Dong Y, Jiang L, Pan Q, Man Y, Wang S, Li J: Augmented NADPH oxidase activity and p22phox expression in monocytes underlie oxidative stress of patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2011, 91(3):371-380.
• [35]Qin F, Simeone M, Patel R: Inhibition of NADPH oxidase reduces myocardial oxidative stress and apoptosis and improves cardiac function in heart failure after myocardial infarction. Free Radic Biol Med 2007, 43(2):271-281.