Evaluating the effects of different fractions obtained from Gundelia tournefortii extract against carbon tetrachloride-induced liver injury in rats

Document Type : Research(Original) Article

Authors

1 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. & Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

2 Shiraz University of Medical Sciences, Pharmaceutical Sciences Research Center

3 Student Research Committee, International branch, Shiraz University of Medical Sciences, Shiraz, Iran

4 Department of Pharmacognosy, School of Pharmacy, Shiraz University of Medical Sciences, International Branch, Shiraz, Iran

5 Food and Drug Organization, Ministry of Health, Tehran, Iran

6 Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Xenobiotics-induced liver injury is a major challenge for clinicians and pharmaceutical industry. Hence, finding new therapeutic molecules against this complication has clinical value. The current investigation aimed to evaluate the potential protective effects of different fractions obtained from Gundelia tournefortii (GT) hydroalcoholic extract in a rat model of acute hepatic injury. Male Sprague-Dawley rats (200‑250 g) were treated with carbon tetrachloride (CCl4) (1.5 ml/kg, i.p), then ethanol, water, chloroform, ethyl acetate, and n-Butanol fractions of GT extract were administered. Biochemical and histopathological markers of hepatic injury were assessed and glutathione (GSH) and lipid peroxidation were monitored in liver samples. CCl4 administration caused hepatotoxicity as revealed by an increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) activity, as well as pathological changes of the liver. Furthermore, a significant reduction in hepatic glutathione content and an elevation in lipid peroxidation were observed in CCl4‑treated rats. It was found that the n‑butanol (200 mg/kg) and the ethyl acetate (300 mg/kg) fractions of GT extract protected liver against CCL4‑induced damage as judged by lower AST, ALT, LDH and lipid peroxidation, prevention of tissue glutathione depletion, and alleviation of histopathological damages of liver in extract‑treated animals. As n‑butanol and the ethyl acetate fractions of GT effectively alleviated the liver injury induced by CCl4 and provide antioxidant properties, we might be able to propose that the hepatoprotective chemicals of Gundelia extract are present in these fractions.

Keywords


  1. References
  2. Lee WM. Drug-induced hepatotoxicity. New Eng J Med. 2003; 349;474-485.
  3. Abdoli N, Heidari R, Azarmi Y, Eghbal MA. Mechanisms of the Statins Cytotoxicity in Freshly Isolated Rat Hepatocytes. J Biochem Mol Toxicol. 2013; 27;287-294.
  4. Heidari R, Niknahad H, Jamshidzadeh A, Eghbal MA, Abdoli N. An Overview on the Proposed Mechanisms of Antithyroid Drugs-Induced Liver Injury. Adv Pharm Bull. 2015; 5;1-11.
  5. Heidari R, Niknahad H, Jamshidzadeh A, Abdoli N. Factors affecting drug-induced liver injury: antithyroid drugs as instances. Clin Mol Hepatol. 2014; 20;237-248.
  6. Yilmaz O, Ersan Y, Ozsahin AD, Ozturk AI, Ozkan Y. Consequences of the Combined α-tocopherol, Ascorbic Acid and α-lipoic Acid on the Glutathione, Cholesterol and Fatty Acid Composition in Muscle and Liver of Diabetic Rats. Iran J Bas Med Sci. 2013; 16;165-172.
  7. Heidari R, Babaei H, Eghbal MA. Cytoprotective effects of taurine against toxicity induced by isoniazid and hydrazine in isolated rat hepatocytes. Arch Indust Hyg Toxicol. 2013; 64;201-210.
  8. Heidari R, Babaei H, Eghbal MA. Amodiaquine-induced toxicity in isolated rat hepatocytes and the cytoprotective effects of taurine and/or N-acetyl cysteine. Res Pharm Sci. 2014; 9;97-105.
  9. Sharma V, Singh M. Attenuation of N-nitrosodimethylamine induced hepatotoxicity by Operculina turpethum in Swiss Albino mice. Iran J Basic Med Sci. 2014; 17;73-80.
  10. Weber LWD, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol. 2003; 33;105-136.
  11. Tong J, Yao X, Zeng H, Zhou G, Chen Y, Ma B, Wang Y. Hepatoprotective activity of flavonoids from Cichorium glandulosum seeds in vitro and in vivo carbon tetrachloride-induced hepatotoxicity. J Ethnopharmacol. 2015; 174;355-363.
  12. Farida T, Salawu OA, Tijani AY, Ejiofor JI. Pharmacological evaluation of Ipomoea asarifolia (Desr.) against carbon tetrachloride-induced hepatotoxicity in rats. J Ethnopharmacol. 2012; 142;642-646.
  13. Niranjana Murthy H, Dandin VS, Yoeup Paek K. Hepatoprotective activity of ginsenosides from Panax ginseng adventitious roots against carbon tetrachloride treated hepatic injury in rats. J Ethnopharmacol. 2014; 158, Part A;442-446.
  14. Jadon A, Bhadauria M, Shukla S. Protective effect of Terminalia belerica Roxb. and gallic acid against carbon tetrachloride induced damage in albino rats. J Ethnopharmacol. 2007; 109;214-218.
  15. Mosaddegh M, Naghibi F, Moazzeni H, Pirani A, Esmaeili S. Ethnobotanical survey of herbal remedies traditionally used in Kohghiluyeh va Boyer Ahmad province of Iran. J Ethnopharmacol. 2012; 141;80-95.
  16. Hajimahmoodi M, Shams-Ardakani M, Saniee P, Siavoshi F, Mehrabani M, Hosseinzadeh H, Foroumadi P, Safavi M, Khanavi M, Akbarzadeh T, others. In vitro antibacterial activity of some Iranian medicinal plant extracts against Helicobacter pylori. Nat Prod Res. 2011; 25;1059-1066.
  17. Ghasemi PA, Momeni M, Bahmani M. Ethnobotanical study of medicinal plants used by Kurd tribe in Dehloran and Abdanan districts, Ilam province, Iran. Afr J Trad Compl Alt Med. 2013; 10;368-385.
  18. Jamshidzadeh A, Fereidooni F, Salehi Z, Niknahad H. Hepatoprotective activity of Gundelia tourenfortii. J Ethnopharmacol. 2005; 101;233-237.
  19. Janbaz KH, Saeed SA, Gilani AH. Protective effect of rutin on paracetamol-and CCl4-induced hepatotoxicity in rodents. Fitoterapia. 2002; 73;557-563.
  20. Mourelle M, Muriel P, Favari L, Franco T. Prevention of ccl4-induced liver cirrhosis by silymarin. Fundament Clin Pharmacol. 1989; 3;183-191.
  21. Kim S-H, Cheon HJ, Yun N, Oh S-T, Shin E, Shim KS, Lee S-M. 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.
  22. Heidari R, Jamshidzadeh A, Keshavarz N, Azarpira N. Mitigation of Methimazole-Induced Hepatic Injury by Taurine in Mice. Sci Pharm. 2014; In Press.
  23. Jamshidzadeh A, Heidari R, Razmjou M, Karimi F, Moein MR, Farshad O, Akbarizadeh AR, Shayesteh MRH. An in vivo and in vitro investigation on hepatoprotective effects of Pimpinella anisum seed essential oil and extracts against carbon tetrachloride-induced toxicity. Iran J Bas Med Sci. 2015; 18;205-211.
  24. Heidari R, Niknahad H, Jamshidzadeh A, Azarpira N, Bazyari M, Najibi A. Carbonyl Traps as Potential Protective Agents against Methimazole-Induced Liver Injury. J Biochem Mol Toxicol. 2015; 29;173-181.
  25. Moezi L, Heidari R, Amirghofran Z, Nekooeian AA, Monabati A, Dehpour AR. Enhanced anti-ulcer effect of pioglitazone on gastric ulcers in cirrhotic rats: The role of nitric oxide and IL-1b. Pharmacol Rep. 2013; 65;134-143.
  26. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968; 25;192-205.
  27. Heidari R, Taheri V, Rahimi HR, Shirazi Yeganeh B, Niknahad H, Najibi A. Sulfasalazine-induced renal injury in rats and the protective role of thiol-reductants. Renal failure. 2015; In Press;1-5.
  28. Heidari R, Babaei H, Roshangar L, Eghbal MA. Effects of enzyme induction and/or glutathione depletion on methimazole-induced hepatotoxicity in mice and the protective role of N-acetylcysteine. Advanc Pharm Bull. 2013; In Press.
  29. Heidari R, Jamshidzadeh A, Keshavarz N, Azarpira N. Mitigation of Methimazole-Induced Hepatic Injury by Taurine in Mice. Sci Pharm. 2015; 83;143-158.
  30. Uchiyama M, Mihara M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978; 86;271-278.
  31. Gaudio E, Onori P, Franchitto A, Sferra R, Riggio O. Liver metabolic zonation and hepatic microcirculation in carbon tetrachloride-induced experimental cirrhosis. Digest Dise Sci. 1997; 42;167-177.
  32. Ritter C, Reinke A, Andrades M, Martins MR, Rocha J, Menna-Barreto S, Quevedo J, Moreira JCF, Dal-Pizzol F. Protective effect of N-acetylcysteine and deferoxamine on carbon tetrachloride-induced acute hepatic failure in rats. Crit Care Med. 2004; 32;2079-2083.
  33. Vargas-Mendoza N, Madrigal-Santillan E, Morales-Gonzalez A, Esquivel-Soto J, Esquivel-Chirino C, Garcia-Luna Y Gonzalez-Rubio M, Gayosso-de-Lucio JA, Morales-Gonzalez JA. Hepatoprotective effect of silymarin. World J Hepatol. 2014; 6;144-149.
  34. Czaja MJ, Xu J, Alt E. Prevention of carbon tetrachloride-induced rat liver injury by soluble tumor necrosis factor receptor. Gastroenterology. 1995; 108;1849-1854.
  35. Weber LWD, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. CRC Crit Rev Toxicol. 2003; 33;105-136.
  36. Sabahi M, Ramezanian M, Jaffari G, Heravi G, Bahaeddini F, Aynehchi Y. Survey of Iranian plants for saponins, alkaloids, flavonoids, and tannins. IV. The plants of Kerman Province. Pharm Biol. 1985; 23;165-175.
  37. Halabi S, Battah AA, Aburjai T, Hudaib M. Phytochemical and Antiplatelet Investigation of Gundelia tournifortii. Pharm Biol. 2005; 43;496-500.
  38. Haghi G, Hatami A, Arshi R. Distribution of caffeic acid derivatives in Gundelia tournefortii L. Food Chem. 2011; 124;1029-1035.
  39. Haghi G, Hatami A. Simultaneous quantification of flavonoids and phenolic acids in plant materials by a newly developed isocratic high-performance liquid chromatography approach. J Agr Food Chem. 2010; 58;10812-10816.
  40. Adzet T, Camarasa J, Laguna JC. Hepatoprotective activity of polyphenolic compounds from Cynara scolymus against CCl4 toxicity in isolated rat hepatocytes. J Nat Prod. 1987; 50;612-617.
  41. Wang M, Simon JE, Aviles IF, He K, Zheng Q-Y, Tadmor Y. Analysis of antioxidative phenolic compounds in artichoke (Cynara scolymus L.). J Agricult Food Chem. 2003; 51;601-608.
  42. Tirkey N, Pilkhwal S, Kuhad A, Chopra K. Hesperidin, a citrus bioflavonoid, decreases the oxidative stress produced by carbon tetrachloride in rat liver and kidney. BMC Pharmacol. 2005; 5.
  43. Tipoe GL, Leung TM, Liong EC, Lau TYH, Fung ML, Nanji AA. Epigallocatechin-3-gallate (EGCG) reduces liver inflammation, oxidative stress and fibrosis in carbon tetrachloride (CCl 4)-induced liver injury in mice. Toxicology. 2010; 273;45-52.
  44. Kapil A, Koul IB, Suri OP. Antihepatotoxic Effects of chlorogenic acid from Anthocephalus cadamba. Phytother Res. 1995; 9;189-193.
  45. Lee KJ, Choi JH, Khanal T, Hwang YP, Chung YC, Jeong HG. Protective effect of caffeic acid phenethyl ester against carbon tetrachloride-induced hepatotoxicity in mice. Toxicology. 2008; 248;18-24.
  46. Pavanato A, Tuñon MJ, Sanchez-Campos S, Marroni CA, Llesuy S, Gonzalez-Gallego J, Marroni N. Effects of quercetin on liver damage in rats with carbon tetrachloride-induced cirrhosis. Dig Dis Sci. 2003; 48;824-829.
  47. Cui Y, Han Y, Yang X, Sun Y, Zhao Y. Protective effects of quercetin and quercetin-5',8-disulfonate against carbon tetrachloride-caused oxidative liver injury in mice. Molecules. 2013; 19;291-305.
  48. Jadon A, Bhadauria M, Shukla S. Protective effect of Terminalia belerica Roxb. and gallic acid against carbon tetrachloride induced damage in albino rats. J Ethnopharmacol. 2007; 109;214-218.
  49. Tung Y-T, Wu J-H, Huang C-C, Peng H-C, Chen Y-L, Yang S-C, Chang S-T. Protective effect of Acacia confusa bark extract and its active compound gallic acid against carbon tetrachloride-induced chronic liver injury in rats. Food Chem Toxicol. 2009; 47;1385-1392.
  50. Halliwell B, Chirico S. Lipid peroxidation: its mechanism, measurement, and significance. American J Clin Nut. 1993; 57;715S-724S.
  51. Forman HJ, Zhang H, Rinna A. Glutathione: Overview of its protective roles, measurement, and biosynthesis. Mol Asp Med. 2009; 30;1-12.
  52. Bhadauria M, Nirala SK, Shukla S. Propolis protects CYP 2E1 enzymatic activity and oxidative stress induced by carbon tetrachloride. Mol Cell Biochem. 2007; 302;215-224.