Lipid-lowering and hepatoprotective effects of Vitis vinifera dried seeds on paracetamol-induced hepatotoxicity in rats

  • Almajwal, Ali Madi (Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University) ;
  • Elsadek, Mohamed Farouk (Nutrition and Food Science Department, Faculty of Home Economics, Helwan University)
  • Received : 2014.04.16
  • Accepted : 2014.09.01
  • Published : 2015.02.01


BACKGROUND/OBJECTIVES: Red grape seeds as functional food are a good source of important bioactive components such as phenolics and antioxidants, which decrease oxidative stress that contributes to the pathogenesis of hepatotoxicity. The current study was conducted in order to evaluate the protective effect of red grape dried seeds (RGDS) on antioxidant properties, lipid metabolism, and liver and kidney functions of rats with paracetamol (750 mg/kg) induced hepatotoxicity. MATERIALS/METHODS: RGDS was added to the basal diet at 5, 10, and 20%. Thirty five adult male rats were assigned to five groups (n = 7) for a six-week feeding period; group (1) normal control, group (2) induced control, groups (3, 4, and 5) fed a diet with RGPS at different levels, 5, 10, and 20%, respectively. At the end of the feeding period, animals' blood and tissues were collected for estimation of serum lipid profile, serum liver, and kidney biomarkers. The protection was measured by detecting lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD), Catalase (CAT) (in liver tissues), and liver histological examination. RESULTS: The results showed a significant (P < 0.05) decrease in levels of serum cholesterol, triglycerides, low density lipoprotein (LDL-C), and very low density lipoprotein (VLDL-C), with a significant increase in level of high density lipoprotein (HDL-C) for RGDS groups compared to induced control. Rats administered a diet containing RGDS levels produced significant (P < 0.05) hepatoprotection by decreasing the activities of liver enzymes, kidney parameters, and lipid peroxidation, while levels of GSH, SOD, and CAT were increased significantly to near the normal levels. CONCLUSION: The RGDS 20% group was more effective than others against hepatotoxicity of paracetamol, which may be attributed to RGDS total phenols and antioxidant contents, which were 1.438 mg and 1.231 mg, respectively.


Supported by : King Saudi University


  1. Halliwell B, Gutteridge JM. Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol 1990;186:1-85.
  2. Steinbrecher UP, Zhang HF, Lougheed M. Role of oxidatively modified LDL in atherosclerosis. Free Radic Biol Med 1990;9:155-68.
  3. Sohn SH, Kim SK, Kim YO, Kim HD, Shin YS, Yang SO, Kim SY, Lee SW. A comparison of antioxidant activity of Korean White and Red Ginsengs on H2O2-induced oxidative stress in HepG2 hepatoma cells. J Ginseng Res 2013;37:442-50.
  4. Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 2012;24:981-90.
  5. Jeon SM, Bok SH, Jang MK, Kim YH, Nam KT, Jeong TS, Park YB, Choi MS. Comparison of antioxidant effects of naringin and probucol in cholesterol-fed rabbits. Clin Chim Acta 2002;317:181-90.
  6. Ghafoor K, Al-Juhaimi F, Choi YH. Effects of grape (vitis labrusca b.) peel and seed extracts on phenolics, antioxidants and anthocyanins in grape juice. Pak J Bot 2011;43:1581-6.
  7. Hassan HM. Protective effects of red grape seed extracts on DNA, brain and erythrocytes against oxidative damage. Glob J Pharmacol 2013;7:241-8.
  8. Shaker ES. Antioxidative effect of extracts from red grape seed and peel on lipid oxidation in oils of sunflower. Lebenson Wiss Technol 2006;39:883-92.
  9. Fujishita K, Ozawa T, Shibata K, Tanabe S, Sato Y, Hisamoto M, Okuda T, Koizumi S. Grape seed extract acting on astrocytes reveals neuronal protection against oxidative stress via interleukin-6-mediated mechanisms. Cell Mol Neurobiol 2009;29:1121-9.
  10. Tsao R. Chemistry and biochemistry of dietary polyphenols. Nutrients 2010;2:1231-46.
  11. Sanchez-Moreno C, Cao G, Ou B, Prior RL. Anthocyanin and proanthocyanidin content in selected white and red wines. Oxygen radical absorbance capacity comparison with nontraditional wines obtained from highbush blueberry. J Agric Food Chem 2003;51:4889-96.
  12. Goni I, Martin N, Saura-Calixto F. In vitro digestibility and intestinal fermentation of grape seed and peel. Food Chem 2005;90:281-6.
  13. da Silva TL, Bernardo EC, Nobre B, Mendes RL, Reis A. Extraction of victoria and red globe grape seed oils using supercritical carbon dioxide with and without ethanol. J Food Lipids 2008;15:356-69.
  14. Slinkard K, Singleton VL. Total phenol analysis; automation and comparison with manual methods. Am J Enol Vitic 1977;28:49-55.
  15. Prieto P, Pineda M, Aguilar M. Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: specific application to the determination of vitamin E. Anal Biochem 1999;269:337-41.
  16. Reeves PG, Nielsen FH, Fahey GC Jr. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 1993;123:1939-51.
  17. Chapman DG, Castillo R, Campbell JA. Evaluation of protein in food: 1. A method for the determination of protein efficiency ratios. Can J Biochem Physiol 1959;37:679-86.
  18. Jaishree V, Badami S. Antioxidant and hepatoprotective effect of swertiamarin from Enicostemma axillare against D-galactosamine induced acute liver damage in rats. J Ethnopharmacol 2010;130: 103-6.
  19. Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957;28:56-63.
  20. King J. The hydrolases-acid and alkaline phosphatases. In: Practical Clinical Enzymology. London: Van Nostrand; 1965 p.191-208.
  21. Patton CJ, Crouch SR. Spectrophotometric and kinetics investigation of the Berthelot reaction for the determination of ammonia. Anal Chem 1977;49:464-9.
  22. Fossati P, Prencipe L, Berti G. Use of 3,5-dichloro-2-hydroxybenzenesulfonic acid/4-aminophenazone chromogenic system in direct enzymic assay of uric acid in serum and urine. Clin Chem 1980; 26:227-31.
  23. Husdan H, Rapoport A. Estimation of creatinine by the Jaffe reaction. A comparison of three methods. Clin Chem 1968;14: 222-38.
  24. Allain CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic determination of total serum cholesterol. Clin Chem 1974;20:470-5.
  25. Bergmeyer HU, Gawehn K. Methods of Enzymatic Analysis. New York (NY): Academic Press; 1974.
  26. Warnick GR, Benderson JM, Albers JJ. Interlaboratory proficiency survey of high-density lipoprotein cholesterol measurement. Clin Chem 1983;29:516-9.
  27. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
  28. Rudnicki M, de Oliveira MR, da Veiga Pereira T, Reginatto FH, Dal-Pizzol F, Moreira JC. Antioxidant and antiglycation properties of Passiflora alata and Passiflora edulis extracts. Food Chem 2007; 100:719-24.
  29. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959; 82:70-7.
  30. Spitz DR, Oberley LW. An assay for superoxide dismutase activity in mammalian tissue homogenates. Anal Biochem 1989;179:8-18.
  31. Sinha AK. Colorimetric assay of catalase. Anal Biochem 1972;47: 389-94.
  32. Tirmenstein MA, Nelson SD. Subcellular binding and effects on calcium homeostasis produced by acetaminophen and a nonhepatotoxic regioisomer, 3'-hydroxyacetanilide, in mouse liver. J Biol Chem 1989;264:9814-9.
  33. Vermeulen NP, Bessems JG, Van de Straat R. Molecular aspects of paracetamol-induced hepatotoxicity and its mechanism-based prevention. Drug Metab Rev 1992;24:367-407.
  34. Kanungo SK, Panda DS, Swain SR, Barik BB, Tripathi DK. Comparative evaluation of hypolipidemic activity of some marketed herbal formulations in triton induced hyperlipidemic rats. Pharmacologyonline 2007;3:211-21.
  35. Duda-Chodak A, Tarko T. Antioxidant properties of different fruit seeds and peels. Acta Sci Pol Technol Aliment 2007;6:29-36.
  36. Patel DK, Patel KA, Patel UK, Thounaojam MC, Jadeja RN, Ansarullah, Padate GS, Salunke SP, Devkar RV, Ramachandran AV. Assessment of lipid lowering effect of Sida rhomboidea. Roxb Methanolic extract in experimentally induced hyperlipidemia. J Young Pharm 2009;1: 233-8.
  37. Pedraza-Chaverri J, Barrera D, Hernandez-Pando R, Medina-Campos ON, Cruz C, Murguia F, Juarez-Nicolas C, Correa-Rotter R, Torres N, Tovar AR. Soy protein diet ameliorates renal nitrotyrosine formation and chronic nephropathy induced by puromycin aminonucleoside. Life Sci 2004;74:987-99.
  38. Yang D, Lin S, Yang D, Wei L, Shang W. Effects of short- and long-term hypercholesterolemia on contrast-induced acute kidney injury. Am J Nephrol 2012;35:80-9.
  39. Hassan HM. Hepatoprotective effect of red grape seed extracts against ethanol-induced cytotoxicity. Glob J Biotechnol Biochem 2012;7:30-7.
  40. Dash DK, Yeligar VC, Nayak SS, Ghosh T, Rajalingam D, Sengupta P, Maiti BC, Maity TK. Evaluation of hepatoprotective and antioxidant activity of Ichnocarpus frutescens (Linn.) R.Br. on paracetamolinduced hepatotoxicity in rats. Trop J Pharm Res 2007;6:755-65.

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