Effects of Green tea extract on liver histopathology and serum biomarkers of hepatic tissue injury in streptozotocin-induced diabetic rats
Subject Areas : Veterinary Clinical PathologyA.A Abolfathi 1 , علی Rezaie 2 , GH Mousavi 3 , M.R Valilou 4 , بهبود Jafari 5
1 - Department of Biological Science, Ahar Branch, Islamic Azad University, Ahar, Iran
2 - Department of Clinical Sciences, Tabriz Branch, Islamic Azad University, Tabriz, Iran
3 - Department of Clinical Sciences, Tabriz Branch, Islamic Azad University, Tabriz, Iran
4 - Department of Veterinary Medicine, Shabestar Branch, Islamic Azad University, Shabestar, Iran
5 - Department of Microbiology, Ahar Branch, Islamic Azad University, Ahar, Iran
Keywords: liver, Diabetes mellitus, Rat, Histopathology, Green tea, Biomarkers of hepatic tissue injury,
Abstract :
The aim of present study was to evaluate the liver injury as a complication of diabetes mellitus and to assess the hepatoprotective properties of Green tea extract in streptozotocin-induced diabetic rats. For this purpose, 40 male Wistar rats were randomly separated into four groups, each containing 10 animals: Group 1, healthy control rats; Group 2, normal rats treated with Green tea extract (1.5%, w/v) was given in drinking water; Group 3, diabetic rats and Group 4, diabetic rats treated with Green tea extract (1.5%, w/v) in drinking water. The extract was injected in intraperitoneal route for a period of 8 weeks. Control groups received normal saline in similar manner. Diabetes was induced by single injection of STZ (75 mg/kg i.p.). At the end of experiment, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin and bilirubin were measured. For histopathological evaluation, tissue specimens were fixed in 10% buffered formalin and 5 micron thick sections with H&E stain were prepared using routine hitopathological techniques. In diabetic rats, serum levels of functional liver markers were found to be significantly increased in comparison with control group (p<0.05), while this markers in diabetic rats treated with Green tea extract significantly decreased as compared to diabetic rats. Histopathological findings were in consistent with biochemical results. The data obtained proved that Green tea extract has hepatoprotective activity against diabetic hepatopathy in streptozotocin-induced diabetic rats.
- Akhtar, M.S. and Iqbal J. 1991. Evaluation of the hypoglycemic effect of achyranthes aspera in normal and alloxan diabetic rabbits. J. Ethnopharmacol., 31: 49-57.
- Athyros, V.G., Mikhailidis, D.P. and Didangelos, T.P. 2006. Effect of multifactorial treat- ment on nonalcoholic fatty liver disease in metabolic syndrome: a randomised study. Curr Med Res Opin., 22:873-883.
- Baynes, J.W. 1991. Role of oxidative stress in the development of complications in diabetes. Diabetes 40:405-412.
- Benelli, R., Vene, R., Bisacchi, D., Garbisa, S. and Albini, A. 2002. Anti-invasive effects of green tea polyphenol epigallocatechin-3-galleate (EGCG), a natural inhibitor of metallo and serine proteases. Biol Chem., 383: 101-105.
- Cameron, N.E., Gibson, T.M., Nangle, M.R. and Cotter, M.A. 2005. Inhibitors of advanced glycation end product formation and neurovascular dysfunction in experimental diabetes. Ann N Y Acad Sci., 1043: 784-792.
- Crespy, V. and Williamson, G. 2004. A review of the health effects of green tea catechins in in vivo animal models, J Nutr., 134: 3431S-3440S.
- Curcio, F., Pegoraro, I., Dello Russo, P., Falleti, E., Perrella, G. and Ceriollo A. 1995. SOD and GSH inhibit the high glucose induced oxidative damage and the PGDF increased secretion in cultured human endothelial cells. Thromb Haemost, 74: 969-973.
- de Marco, R., Locatelli, F., Zoppini, G., Verlato, G., Bonora, E. and Muggeo, M. 1999. Cause-specific mortality in type 2 diabetes: The Verona Diabetes Study. Diabetes Care, 22:756-761.
- Drotman, R. and Lawhan, G. 1978. Serum enzymes are indications of chemical induced liver damage. Drug Chem Toxicol., 1(2): 163-171.
- Eddouks, M., Maghrani, M. and Michel, J.B. 2005. Hypoglycaemic effect of Triticum repens P. Beauv. in normal and diabetic rats. Journal of Ethnopharmacology, 102( 2): 228-232.
- Feillet-Coudray, C., Rock, E., Coudray, C., Grzelkowska, K., Azais-Braesco, V., Dardevet D. and Mazur, A. 1999. Lipid peroxidation and antioxidant status in experimental diabetes. Clinica Chimica Acta., 284(1): 31-43.
- Griesmacher, A., KinderHauser, M. and Andert, S. 1995. Enhanced serum levels of thiobarbituric acid-reactive substances in diabetes mellitus. Am J Med., 98:469-475.
- Gupta, R.K., Kesari, A.N., Murthy, P.S., Chandra, R., Tandon, V. and Watal, G. 2005. Hypoglycemic and antidiabetic effect of ethanolic extract of leaves of Annona squamosa L. in experimental animals. Journal of Ethnopharmacology, 99(1): 75-81.
- Halliwell, B. and Gutteridge, J.M.C. 1989. Free radicals in biology and medicine (2nd ed.), Clarendon Press, Oxford.
- Harris, E.H. 2005. Elevated Liver Function Tests in Type 2 Diabetes. Clinical diabetes, 23(3): 115-119.
- Hendriksen, P.H., Oey, P.L., Wieneke, G.H., Bravenboer, B. and Banga, J.D. 1992. Subclinical diabetic neuropathy: similarities between electrophysiological results of patients with type 1 (insulin-dependent) and type 2 (non-insulin dependent) diabetes mellitus, Diabetologia, 35: 690-695.
- Jacqueline, M.S., Jongsoon, L. and Paul, F.P. 1997. Tumor necrosis factor-α -induced insulin resistance in 3T3- L1 adipocytes is accompanied by a loss of insulin receptor substrate-1 and GLUT4 expression without a loss of insulin receptor-mediated signal transduction. J Biol Chem., 272(2): 971-976.
- Jandeleit-Dahm, K.A., Lassila, M. and Allen, T.J. 2005. Advanced glycation end products in diabetes-associated atherosclerosis and renal disease: interventional studies. Ann N Y Acad Sci., 1043: 759-766.
- Jennings, P.B., Chirico, S. Jones, A.F., Lunec, J. and Barnett, A.H. 1987. Vitamin C metabolites and microangiopathy in diabetes mellitus. Diab Res., 6:151-154.
- Jin, X., Zheng, R.H. and Li, Y.M. 2008. Green tea consumption and liver disease: a systematic review. Liver Int. 28(7): 990-996.
- Kakkar, R., Kalra, J., Mantha, S.V. and Prasad, K. 1995. Lipid peroxidation and activity of antioxidant enzymes in diabetic rats. Mol Cell Biochem., 151: 113-119.
- Kakkar, R., Mantha, S.V., Radhi, J., Prasad K. and Kalra, J. 1998. Increased oxidative stress in rat liver and pancreas during progression of streptozotocin-induced diabetes. J Clin Sci., 94: 623-632.
- Kalia, K., Sharma, S., Mistry, K. 2004. Non-enzymatic glycosylation of immunoglobulins in diabetic nephropathy. Clinical & Chemical Acta., 347(1-2): 169-176.
- Kasahara, T. and Kato, T. 1993. A new redox-cofactor vitamin for mammals. Nature, 422:832
- Kaszkin, M., Beck K-F., Eberhardt, W. and Pfeilschfter, J. 2004. Unravelling green tea's mechanisms of action: More than meets the eye. Mol Pharmacol., 65: 15-17.
- Kind, P.R. and King, E.J. 1954. Estimation of plasma phosphates by determination of hydrolyzed phenol with antipyrin. J Clin Pathol., 7(4): 322-326.
- Kobayashi, Y., Suzuki, M., Satsu, H., Arai, S., Hara, Y., Suzuki, K., Miyamaoto, Y., Shimizu, M. 2000. Green tea polyphenols inhibit the sodium-dependent glucose transporter of intestinal epithelial cells by a competitive mechanism. J Agric Food Chem., 48: 5618-5623.
- Liu, H.R., Tang, X.Y., Dai, D.Z. and Dai, Y. 2008. Ethanol extracts of Rehmannia complex (Di Huang) containing no corni fructus improve early diabetic nephropathy by combining suppression on the ET-ROS axis with modulate hypoglycemic effect in rats. J Ethnopharmacol., 118(3): 466-472.
- Loew, D. and Kaszkin, M. 2002. Approaching the problem of bioequivalence of herbal medicinal products. Phytother Res., 16: 705-711.
- Lowry, O.H., Rosebrough, N.J. and Farr, A.L. 1951. Protein measurement with the folin phenol reagent. J Biol Chem., 193(1): 265-275.
- MacRury, S.M., Gordon, D. and Wilson, R. 1993. A comparison of different methods of assessing free radical diabetes and peripheral vascular disease. Diabet Med., 10:331-335.
- Maity, S., Vadasiromoni, J. and Ganguly, D. 1998. Role of glutathione in the antiulcer effect of hot water extract of black tea, Jpn J Pharmacol., 78: 285-292.
- Malloy, H.T. and Evelyn, K.A. 1937. The determination of bilirubin level with the photoelectric colorimeter. J Biol Chem., 119(2): 481-484.
- McLennan, S.V., Heffernen, S. and Wright L. 1991. Changes in hepatic glutathione metabolism in diabetes. Diabetes 40: 344-348.
- Mehana, E.E., Meki, A.R. and Fazili, K.M. 2010. Ameliorated effects of green tea extract on lead induced liver toxicity in rats Exp Toxicol Pathol., In press.
- Mullarkey, C.J., Edelstein, D. and Brownlee, L. 1990. Free radical generation by early glycation products: a mechanism for accelerated atherogenesis in diabetes. Biochem Biophys Res Commun 173:932-939.
- Muriel, P., Garcipiana, T., Perez-Adverez, V., Mourelle, M. 1992. Silymarin protects against paracetamol-induced lipid peroxidation and liver damage. J Applied Toxicol., 12(6): 439-442.
- Niskanen, L.K., Salonen, J.T., Nyssonen, K. and Uusitupa, M.I.J. 1995. Plasma lipid peroxidation and hyperglycemia: a connection through hyperinsulinaemia?. Diabet Med., 12: 802-808
- Ramesh, B. and Pugalendi, K.V. 2006. Impact of umbelliferone (7-hydroxycoumarin) on hepatic marker enzymes in streptozotocin diabetic rats. Indian J Pharmacol., 38(3): 209-210.
- Ramesh, B., Viswanathan, P. and Pugalendi, K.V. 2007. Protective effect of Umbelliferone on membranous fatty acid composition in streptozotocin-induced diabetic rats. European Journal of Pharmacology, 566(1-3): 231-239.
- Reitman, S. and Frankel, S. 1957. A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminase. Am J Clin Pathol., 28(1): 56-63.
- Ritz, E., Hasslacher, C. and Tschope, W. 1990. Diabetic nephropathy — are there differences between type I and type II?, Miner Electrolyte Metab., 16: 69-72.
- Ryu, O.H., Lee, J. and Lee, K.W. 2006. Effects of green tea consumption on inflammation, insulin resistance and pulse wave velocity in type 2 diabetes patients. Diabetes Res Clin Pract., 71(3): 356-358.
- Sabu, M.C., Smitha, K. and Kuttan, R. 2002. Anti-diabetic activity of green tea polyphenols and their role in reducing oxidative stress in experimental diabetes. J Ethnopharmacol, 83: 109-116.
- Salah, N., Miller, N.J., Paganga, G., Tijburg, L., Bolwell, G.P. and Rice-Evans, C. 1995. Polyphenolic flavanols as scavengers of aqueous phase radicals and as chain-breaking antioxidants. Arch Biochem Biophys., 322:339-346.
- Strain, J.J. 1991. Disturbances of micronutriment and antioxidant status in diabetes. Proc Nutr Soc., 50: 591-604.
- Sundaram, R.K., Bhaskar, A., Vijayalingam, S., Viswanatthan, M., Moha, R. and Shaninugasundaram, K.R. 1996. Antioxidant status and lipid peroxidation in type II diabetes mellitus with and without complications. Clin Sci., 90: 255-260.
- Terao, J., Piskula, M. and Yao, Q. 1994. Protective effect of epicatechin, epicatechin gallate, and quercetin on lipid peroxidation in phospholipid bilayers. Arch Biochem Biophys, 308: 278-284.
- Thabrew, M. and Joice, P. 1987. A comparative study of the efficacy of Pavetta indica and Osbeckia octanda in the treatment of liver dysfunction. Planta Med., 53(3): 239-241.
- Tsuneki, H., Ishizuka, M., Terasawa, M., Wu, J-B., Sasaoka, T. and Kimura, I. 2004. Effect of green tea on blood glucose levels and serum proteomic patterns in diabetic (db/db) mice and on glucose metabolism in healthy humans. BMC Pharmacology, 4:18.
- Tolman, K.G., Fonseca, V., Dalpiaz, A. and Tan, M.H. 2007. Spectrum of Liver Disease in Type 2 Diabetes and Management of Patients With Diabetes and Liver Disease. Diabetes care, 30(3): 734-743.
- Velazques, B., Winocour, P.H., Kesteven, P., Alberti, K.G.M.M. and Lakeer, M.F. 1991. Relation of lipid peroxides to macrovascular disease in type 2 diabetes. Diabet Med 8: 752-758.
- Vestra, M.D. and Fioretto, P. 2003. Diabetic nephropathy: renal structural studies in type 1 and type 2 diabetic patients. Internatrional Congress Series, 1253: 163-169.
- Wang, W. and Goodman, M.T. 1999. Antioxidant property of dietary phenolic agents in a human LDL-oxidation ex vivo model: interaction of protein binding activity. Nutr Res., 19:191-202.
- Weisburger, J.H. and Chung, F.L. 2002. Mechanisms of chronic diseases causation by nutritional factors and tobacco products and their prevention by tea polyphenols. Food Chem Toxicol., 40:1145-1154.
- Wilson, R.L. 1998. Free radicals and tissue damage, mechanistic evidence from radiation studies. In: Biochemical mechanisms of Liver Injury. New York, Academic Press, 123-125.
- Wu, L-Y., Juan, C-C., Ho, L-T., Hsu, Y-P., Hwang, L-S. 2004. Effect of green tea supplementation on insulin sensitivity in Sprague-Dawley rats. J Agric Food Chem., 52: 643-648.
- Wu, L.Y., Juan, C.C., Hwang, L.S., Hsu, Y.P., Ho, P.H. and Ho, L.T. 2004. Green tea supplementation ameliorates insulin resistance and increases glucose transporter IV content in a fructose-fed rat model. Eur J Nutr, 43: 116-124.
- Young, I.S., Torney, J.J. and Trimble, E.R. 1992. The effect of ascorbate supplementation on oxidative stress in the streptozotocin diabetic rat. Free Rad Biol Med., 13:41-46.