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BMC Complementary Medicine and Therapies

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Open Access 01-12-2014 | Research article

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

Authors: Sarawoot Palipoch, Chuchard Punsawad, Phanit Koomhin, Prasit Suwannalert

Published in: BMC Complementary Medicine and Therapies | Issue 1/2014

Abstract

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.

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Rabik CA, Dolan ME: Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev. 2007, 33: 9-23. 10.1016/j.ctrv.2006.09.006.CrossRefPubMed

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. 10.1016/j.phrs.2008.01.001.CrossRefPubMed

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. 10.1293/tox.26.293.CrossRefPubMedPubMedCentral

Arany I, Safirstein RL: Cisplatin nephrotoxicity. Semin Nephrol. 2003, 23: 460-464. 10.1016/S0270-9295(03)00089-5.CrossRefPubMed

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. 10.1016/S0968-4328(01)00006-3.CrossRefPubMed

MacNee W: Oxidative stress and lung inflammation in airways disease. Eur J Pharmacol. 2001, 429 (1–3): 195-207.CrossRefPubMed

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.PubMedPubMedCentral

Babior BM: NADPH oxidase. Curr Opin Immunol. 2004, 16: 42-47. 10.1016/j.coi.2003.12.001.CrossRefPubMed

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. 10.1016/j.taap.2011.04.022.CrossRefPubMed

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. 10.1016/j.peptides.2011.08.027.CrossRefPubMed

11.

Muller FL, Song W, Liu Y, Chaudhuri A, Pieke-Dahl S, Strong R, Huang T-T, Epstein CJ, Roberts LJ, 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. 10.1016/j.freeradbiomed.2006.01.036.CrossRefPubMed

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. 10.1053/jhep.2003.50450.CrossRefPubMed

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. 10.1016/j.jhep.2009.01.030.CrossRefPubMed

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. 10.1016/S0301-4622(99)00070-8.CrossRefPubMed

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.CrossRefPubMed

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.CrossRef

17.

Rashed LA, Hashem RM, Soliman HM: Oxytocin inhibits NADPH oxidase and P38 MAPK in cisplatin-induced nephrotoxicity. Biomed Pharmacother. 2011, 65: 474-480. 10.1016/j.biopha.2011.07.001.CrossRefPubMed

18.

Horton AA, Fairhurst S: Lipid peroxidation and mechanisms of toxicity. Crit Rev Toxicol. 1987, 18 (1): 27-79. 10.3109/10408448709089856.CrossRefPubMed

19.

Etsuo N: Lipid peroxidation: Physiological levels and dual biological effects. Free Radic Biol Med. 2009, 47 (5): 469-484. 10.1016/j.freeradbiomed.2009.05.032.CrossRef

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. 10.1016/j.etp.2009.02.066.CrossRefPubMed

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.CrossRefPubMed

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. 10.1016/j.freeradbiomed.2011.07.018.CrossRefPubMed

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. 10.1016/j.biocel.2008.06.010.CrossRefPubMed

24.

Maheshwari RK, Singh AK, Gaddipati J, Srimal RC: Multiple biological activities of curcumin: a short review. Life Sci. 2006, 78 (18): 2081-2087. 10.1016/j.lfs.2005.12.007.CrossRefPubMed

25.

Ak T, Gülçin İ: Antioxidant and radical scavenging properties of curcumin. Chem Biol Interact. 2008, 174 (1): 27-37. 10.1016/j.cbi.2008.05.003.CrossRefPubMed

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.CrossRef

27.

Jayaprakasha GK, Jaganmohan Rao L, Sakariah KK: Antioxidant activities of curcumin, demethoxycurcumin and bisdemethoxycurcumin. Food Chem. 2006, 98 (4): 720-724. 10.1016/j.foodchem.2005.06.037.CrossRef

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. 10.1016/j.etp.2010.03.001.CrossRefPubMed

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.CrossRefPubMed

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. 10.1016/j.fct.2006.07.017.CrossRefPubMed

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. 10.1016/j.pestbp.2007.08.002.CrossRef

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. 10.1016/j.foodchem.2012.02.009.CrossRef

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. 10.1016/j.cbi.2009.11.004.CrossRefPubMed

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. 10.1016/j.diabres.2010.12.026.CrossRefPubMed

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. 10.1016/j.freeradbiomed.2007.04.021.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6882/14/111/prepub

Title: Hepatoprotective effect of curcumin and alpha-tocopherol against cisplatin-induced oxidative stress
Authors: Sarawoot Palipoch
Chuchard Punsawad
Phanit Koomhin
Prasit Suwannalert
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2014
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/1472-6882-14-111

2024 ASCO Annual Meeting

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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