TY - JOUR TT - The Effects of Curcuma Longa and Silybum Marianum on Carbon Tetrachloride Induced Chronic Hepatic Damage in Rats AU - Atasever, Ayhan AU - Baran, Oktay AU - Ekebaş, Görkem PY - 2017 DA - December JF - Sağlık Bilimleri Dergisi PB - Erciyes Üniversitesi WT - DergiPark SN - 1018-3655 SP - 240 EP - 248 VL - 26 IS - 3 KW - Karaciğer hasarı KW - karbon tetraklorür KW - meryemana dikeni KW - rat KW - zerdeçal. N2 - This study aims to evaluate the protective efficacy of Curcuma longa and Silybum marianum on lipid peroxidation and some serum biochemical parameters in liver damage induced with carbon tetrachloride (CCl4) in rats. In the study, 60 4 month old Wistar albino rats weighing 250gr on average were used. Application of the treatment in the control groups were performed with three groups. The group I was administered corn oil twice for one week, group V was administered 100 mg/kg silymarin and group VI was administrated 80 mg/kg turmeric for 12 weeks by oral gavage. In the experimental group, 0,5 ml/kg CCl4 was injected intraperitoneally twice a week (Group II). The application of the treatment was performed in two groups for 12 weeks in the treatment groups. While the 100 mg/kg silymarin was given in the CCl4+silymarin group by gavage (Group III), the 80 mg/kg turmeric was given in the CCl4+turmeric group following of the injection of 0,5 ml/kg CCl4 (Group IV). At the end of the study, all liver tissues were examined with both histopathological and serum biochemical parameters. While the normal tissue structure was observed in the control group in the histopathological examination of the experimental and control groups, it was shown that there were fatty degeneration in the hepatocytes, deterioration in the structure of remark cords, hepatocyte degeneration, mononuclear cell infiltration areas composed of majority lymphocytes in the portal area and parenchyma, especially at portal area increasing connective tissue spread to parenchyma due to formation of lobulation. The liver lesions were found in the CCl4+silymarin and CCl4+turmeric groups as in Group II. While serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), low density lipoprotein (LDL) levels, liver malondialdehyde (MDA) and nitric oxide (NO) were increased in the CCl4-treated groups; the levels of high-density lipoprotein (HDL) and albumin values were decreased compared to the control group. When compared with the CCl4-treated group, it was observed that there was no statistically significant difference in the serum levels of CCl4+silymarin and CCl4+turmeric groups. It was observed that the serum biochemistry parameters were not significant change in the silymarin and turmeric groups compared with control group. In this study it has been concluded that there is a need for future studies in which different doses of silymarin and turmeric are used to reverse the liver damage and determine their efficacy. CR - 1. Dündar Y. Fitokimyasallar ve sağlıklı yaşam. Kocatepe Tıp Dergisi 2001; 2:131-138. CR - 2. Burroughs AK, Westaby D. Liver, biliary tract and pancreatic disease. In: Kumar P, Clark M (eds), Clinical Medicine. 6 th ed. Elsevier Saunders, 2005; pp 347-417. CR - 3. Moeller RB. Hepatobiliary system. In: Plumlee KH. (ed), Clinical Veterinary Toxicology. United States 2004: pp 61-62. CR - 4. Sherlock S. Chronic hepatitis and cirrhosis. Hepatology 1984; 4:5-28. CR - 5. Natarajan SK, Thomas S, Ramamoorthy P, et al. Oxidative stress in the development of two different experimental models. J Gastroen Hepatol 2006; 21:947-957. CR - 6. McCord JM. The evolution of free radicals and oxidative stress. Am J Meb 2000; 108:652. 7. Betteridge DJ. What is oxidative stress? Metabolism 2000; 49:3-8. CR - 8. Aruoma OI. Nutrition and health aspects of free radicals and antioxidants. Food Chem, 1994; 32:671-683. CR - 9. Halliwell B. How to characterize a biological antioxidant. Free Radical Res Commun 1990; 9:1-32. CR - 10. Southorn PA, Powis G. Free radicals in medicine. Chemical 1988; 29:1516-1523. CR - 11. Sies H. Oxidative stress: Oxidants and antioxidants. Exp Physiol 1997; 82:291-295. CR - 12. Palmieri B, Sblendorio V. Oxidative stress detection: What for? Eur Rev Med Pharmacol Sci 2006; 10:291-317. CR - 13. Moure A, Cruz JM, Franco D, et al. Natural antioxidants from residual sources. Food Chemistry 2001; 72:145-171. CR - 14. Naczk M, Shahidi F. Extraction and analysis of phenolics in food. Journal of Chromatography 2004; 1054:95-111. CR - 15. Muriel P, Espinoza YR. Beneficial drugs for liver disease: A review. J Appl Toxicol 2008; 28:93-103. CR - 16. Anthony KP, Saleh MA. Free radical scavenging and antioxidant activities of silymarin components. Antioxidants 2013; 2:398-407. CR - 17. Muriel P, Mourelle M. Prevention by silymarin of membrane alterations in acute carbon tetrachloride liver damage. J Appl Toxicol 1990; 10:275-279. CR - 18. Wang DH, Ishii K, Zhen LX, Taketa K. Enhanced liver injury in acatalasemic mice following exposure to carbon tetrachloride. Arch Toxicol 1996; 70:189-194. CR - 19. Eminzade S, Uras F, Izzettin FV. Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals. Nutr Metab 2008; 5:18. CR - 20. Das KC, Das CK. Curcumin (diferuloylmethane), a singlet oxygen (1O2) quencher. Biochemical and Biophysical Research Communications 2002; 295,62–66. CR - 21. Naik SR, Thakare VN, Paitl SR. Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: Evidence of its antioxidant property. Exp Toxicol Pathol 2011; 63:419-431. CR - 22. Maheswari RK, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: A short review. Life Sci 2006; 78:2081-2087. CR - 23. Ammon HP, Walh MA. Pharmacology of Curcuma longa. Planta Med 1991; 57:1-7. CR - 24. Luper S. A review of plants used in the treatment liver disease. Altern Med Rev 1998; 3:410-421. CR - 25. Sung-Hwa K, Ho JC, Nari Y, Oh ST, Shin E, Shim KS, Lee SM. Protective effect of a mixture of Aloe vera and Silybum marianum against carbon tetrachloride induced acute hepatotoxicity and liver fibrosis. J Pharmacol Sci 2009; 109:119-127. CR - 26. Kamalakkannan N, Rukkumani R, Varma PS, Viswanathan P, Rajasekharan KN, Menon VP: Comparative effects of curcumin and an analogue of curcumin in carbon tetrachloride induced hepatotoxicity in rats. Basic Clin Pharmacol 2005; 97:15- 21. CR - 27. Lowry OH, Rosebrough NJ, Farr AL Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193:265-75. CR - 28. Miller NJ, Rice-Evans C, Davies MJ, Gopinathan V. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci 1993; 84:407. CR - 29. Yoshioka T, Kawada K, Shimada T. Lipid peroxidation in material and cord blood and protective mechanism against activatedoxygen toxicity in the blood. Am J Obstet Gynecol 1979; 135:372-376. CR - 30. Tracey WR, Tse J, Carter G. Lipopolysaccharideinduced changes in plasma nitrite and nitrate concentrations in rats and mice: Pharmacological evaluation of nitric oxide synthase inhibitors. J Pharmacol Exp Ther 1995; 272:1011-1015. CR - 31. Shimiziu I. Antifibrogenic therapies in chronic HCV infection. Curr Drug Targets Infect Disord 2001; 1:227-240. CR - 32. Hagerman AE, Riedl KM, Jones GA, Sovik KN, Ritchard NT, Hartzfeld PW, Riechel TL. High molecular weight plant polyphenolics (tannins) as biological antioxidants. J Agric Food Chem 1998; 46:1887-1892. CR - 33. Fu Y, Zheng S, Lin J, Ryerse J, Chen A. Curcumin protects the rat liver from CCl4 caused injury and fibrogenesis by attenuating oxidative stres and suppressing inflammation. Mol Pharmacol 2008; 73:399-409. CR - 34. Kevin PA, Mahmoud AS. Free radical scavenging and antioxidant activities of silymarin components. Antioxidants 2013; 2:398-407. CR - 35. Tamayo RP. Is cirrhosis of the liver experimentally produced by CCl4 and adequate model of human cirrhosis? Hepatology 1983; 3:112-120. CR - 36. Recknagel RO, Glende EA, Dolak JA, Waller RL. Mechanism of carbon tetrachloride toxicity. Pharmacol Ther 1989; 43:139-154. CR - 37. Sarhan NAZ, El-Denshary ES, Hassan NS, AbuSalem FM, Abdel-Wahhab MA. Isoflavones enriched soy protein prevents CCl4-induced hepatotoxicity in rats. ISRN Pharmacol 2012; 8. CR - 38. Eidi A, Mortazavi P, Behzadi K, Rohani AH, Safi S. Hepatoprotective effect of manganese chloride against CCl4-induced liver injury in rats. Biol Trace Elem Res 2013; 155:267-275. CR - 39. Lee TY, Wang GJ, Chiu JH, Lin HC. Long-term administration of Salvia miltiorrhiza ameliorates carbon tetrachloride induced hepatic fibrosis in rats. J Pharm Pharmacol 2003; 55:1561-1568. CR - 40. Kus I, Ogeturk M, Oner H, Sahin S, Yekeler H, Sarsilmaz M. Protective effects of melatonin against carbontetrachloride induced hepatotoxicity in rats: A light microscopic and biochemical study. Cell Biochem Funct 2005; 23:169-174. CR - 41. Chamulitrat W, Jordan SJ, Mason RP. Nitric oxide production during endotoxic shock in carbon tetrachloride treated rats. Mol Pharm 1994; 46:391- 397. CR - 42. Srinivasan M, Rukkumani A. Sudheer R, Menon VP. Ferulic acid, a natural protector against carbon tetrachloride induced toxicity. Fundam Clin Pharmacol 2005; 19:491-496. CR - 43. Yılmaz S, Bahçecioğlu İH. Karbon tetraklorür ile siroz oluşturulmuş ratlarda lipid peroksidasyonu, antioksidan enzim ve pirüvat kinaz aktiviteleri. Turk J Vet Anim Sci 2000; 24:25-28. CR - 44. Wu SJ, Lin YH, Chu CC, Tsai YH, Chao JCJ. Curcuminor saikosaponin a improves hepatic antioxidant capacity and protects against CCl4-induced liver injury in rats. J Med Food 2008; 11:224-229. CR - 45. Rajesh MG, Latha MS. Preliminary evaluation of the antihepatotoxic activity of Kamilari, a polyherbal formulation. J Ethanopharmacol 2004; 91:99-104. CR - 46. Muriel P, Moreno MG, Hernandez MC, Chávez E, Alcantar LK. Resolution of liver fibrosis in CCl4 administration in the rat after discontinuation of treatment: Effect of silymarin, silibinin, colchicine and trimethyl colchicinic acid. Basic Clin Pharmacol Toxicol 2005; 96:375-380. CR - 47. Tsai JH, Liu JY, Wu TT, et al. Effects of silymarin on the resolution of liver fibrosis induced by carbon tetrachloride in rats. J Viral Hepatitis 2008; 15:508- -514. CR - 48. Park EJ, Jeon CH, Ko G, Kim J, Sohn DH. Protective effect of curcumin in rat liver injury induced by carbon tetrachloride. J Pharm Pharmacol 2000; 52:437-440. UR - https://dergipark.org.tr/tr/pub/eujhs/article/553096 L1 - https://dergipark.org.tr/tr/download/article-file/693935 ER -