Nurşah BAŞOL, Cansel ÖZMEN, Seda OCAKLI, Selçuk ÇETİN

Evaluation of the effects of curcumin, erdosteine, vitamin E and vitamin C on paracetamol toxicity

Paracetamol toxicity is one of the most common causes of drug induced toxicity in the world. This study aims to investigate the efficacy of curcumin, erdosteine, vitamin E and vitamin C administration in paracetamol-induced liver damage in comparison with N-acetyl cysteine (NAC) in the treatment and prevention of liver toxicity due to paracetamol poisoning. 49 Wistar-Albino rats were used for this study. The rats were randomly divided into 7 groups. Group 1, which was the control group, received no drug administration. All the other groups received the minimum toxic dosage of paracetamol (1 gr/kg). Group 2 was not administered any other drug. Curcumin (100 mg/kg) was administered to Group 3. Group 4 received Vitamin E (170 mg/kg) and Group 5 received Vitamin C (300 mg/kg). Erdosteine (150 mg/kg) was administered to Group 6 and the last group (group 7) was received NAC for 2 days. After 72 hours, the experiment was completed. Liver and kidney tissues and blood samples were collected. AST and ALT values were higher in PCT group compared with the control group. Additionally, in PCT group, SOD and GSH-PX levels were lower while MDA levels were found to be higher in comparison to the control group. In the treatment groups, curcumin proved to be the most efficient agent, with NAC and erdosteine following. Histopathological images supported that curcumin played a key role in preventing liver damage. On the other hand, the results indicated no significant contribution of vitamin E and C in reducing paracetamol induced liver damage. In the light of the results, it is indicated that oxidative stress and lipid peroxidation are principal mechanisms of paracetamol induced liver damage, whereas curcumin and erdosteine are efficient agents in preventing said damage. Furthermore, the findings of the study suggest that curcumin in particular can be used as an alternative drug to NAC after further research on humans.

PDF

___

1. Guggenheimer J, Moore PA. The therapeutic applications of and risks associated with acetaminophen use: a review and update. J Am Dent Assoc. 2011;142:38-44.
2. Lee WM. Acetaminophen toxicity: Changing Perceptions on a Social/ Medical Issue. Hepatology. 2007;46:966-70.
3. Larson AM, Polson J, Fontana RJ, et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005;42:1364-72.
4. Akkose S, Bulut M, Armagan E, et al. Acute poisoning in adults in the years 1996-2001 treated in the Uludag University Hospital, Marmara Region, Turkey. Clinical Toxicology (Phila). 2005;43:105-9.
5. Burke A, Smyth EM, Fitzgerald GA. Analgesic-antipyretic agents: pharmacotherapy of gout. In: Brunton LL, Lazo JS, Parker K, eds, Goodman and Gilman’s the Pharmacological Basis of Therapeutics. 11th edition. McGraw-Hill, New York, 2006; 671-716.
6. Makin AJ, Williams R. Acetaminophen-induced hepatotoxicity: predisposing factors and treatments. Advances Int Med. 1997;42:453-83.
7. Schilling A, Corey R, Leonard M, Eghtesad B. Acetaminophen: old drug, new warnings. Cleveland Clin J Med. 2010;77:19-27.
8. Larson AM. Acetaminophen hepatotoxicity. Clinics in liver disease. 2007;11:525-48.
9. Brok J, Buckley N, Gluud C. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database of Systematic Reviews. 2006;CD003328.
10. Waring WS, Jamie H, Leggett GE. Delayed onset of acute renal failure after significant paracetamol overdose: a case series. Hum Exp Toxicol. 2010;29:63–8.
11. Mercan U. Importance of Free Radicals in Toxicology. Van Vet. J. 2004;15:91-6.
12. Piper JT, Singhal SS, Salameh M, et al. Mechanisms of anticarcinogenic properties of curcumin: the effect of curcumin on glutathione linked detoxification enzymes in rat liver. Int J Biochem Cell Biol. 30; 445–56.
13. Akpolat M, Topçu Y, Kanter M. Investigation Protective Effects of Curcumin and Vitamin C on Ionizing Radiation-Induced Morphological Destruction of Intestinal Mucosa in Rats. J Med Invest. 2008;6:77-85.
14. Baniasadi S, Eftekhari P, Tabarsi P, et al. Protective effect of N-acetylcysteine on antituberculosis druginduced hepatotoxicity. Eur J Gastroenterol Hepatol. 2010;22:1235–8.
15. Dechant KL, Noble S. Erdosteine. Drugs. 1996;52:875–81.
16. Dökmenci İ. Farmakoloji Temel Kavramlar (Pharmacology Basic Concepts). Nobel Tıp Kitabevi, İstanbul, 2000;406:153–9.
17. Kayaalp SO. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji (Medical Pharmacology in terms of Rational Treatment). Hacettepe-Taş Kitapçılık Ltd.Şti, Ankara, 2005;125–9;848–50.
18. Dworkin PD. NMS Pediatri (NMS Pediatrics), 3rd. edition. Nobel Tıp Kitabevi, İstanbul, 2000;53-7.
19. Hinson JA. Reactive metabolites of phenacetin and acetaminophen. environmental health perspectives. University of Melbourne. Australia. 1983;49:71-9.
20. Potter DW, Hinson JA. Mechanisms of Acetaminophen Oxidation to N-Acetyl- benzoquinone imine by horseradish peroxidase and cytochrome P-450. The Journal of Biological Chemistry. 1987;3:966-73.
21. Ranganathan S. Sri, Sathiadas MG, Sumanasena S, et al. Fulminant hepatic failure and paracetamol overuse with Therapeutic intent in febrile children. The Indian Journal of Pediatrics. 2006;73: 871-5.
22. Lauterburg BH, Corcoran GB, Mitchell JR. Mechanism of Action of N-Acetylcysteine in the protection against the hepatotoxicity of acetaminophen in rats in vivo. J Clin Invest. 1983;71:980-91.
23. James LP, Mayeux PR, Hinson JA. Acetaminophen-Induced Hepatotoxicity: Drug Metabolism and Disposition. 2003;31:1499-506.
24. Lei XG, Zhu JH, Mcclung JP, et al. Mice deficient in Cu, Zn-superoxide dismutase are resistant to acetaminophen toxicity. Biochem J. 2006;399:455- 61.
25. Kim SJ, Lee MY, Kwon DY, et al. Alteration in metabolism and toxicity of acetaminophen upon repeated administration in rats. J Pharmacol Sci. 2009;111:175-81.
26. Zhu JH, Zhang X, McClung JP, et al. Impact of cu, zn-superoxide dismutase and se-dependent glutathione peroxidase-1 knockouts on acetaminopheninduced cell death and related signaling in murine liver. Exp Biol Med. 2006;231:1726-32.
27. Cheng WH, Quimby FW, Lei XG. Impacts of glutathione peroxidase-1 knockout on the protection by injected selenium against the pro-oxidantinduced liver aponecrosis and signaling in selenium-deficient mice. Free Radic Biol Med. 2003;34:918-27.
28. Farag MM, Mohamed MB, Youssef EA. Assessment of hepatic function, oxidant/antioxidant status, and histopathological changes inrats treated with atorvastatin: Effect of dose and acute intoxication with acetaminophen. Hum Exp Toxicol. 2015;34:828-37.
29. Jaeschke H, Knight TR, Bajt ML. The role of oxidant stres and reactive nitrogen species in acetaminophen hepatotoxicity. Toxicology Letters. 2003;144:279-88.
30. Atkuri KR, Mantovani JJ, Herzenberg LA, et al. NAcetylcysteine - a Safe antidote for cysteine/glutathione deficiency. Current Opinion in Pharmacology. 2007;7:355-9
31. Saritas A, Kandis H, Baltaci D, et al. N-Acetyl cysteine and erdosteine treatment in acetaminophen-induced liver damage. Toxicol Ind Health. 2014;30:670-8.
32. Li G, Chen JB, Wang C, et al. Curcumin protects against acetaminopheninduced apoptosis in hepatic injury. World J Gastroenterol. 2013;14:7440-6.