THERAPEUTIC EFFICACY OF ISOLATED STIGMA-5,22 DIEN-3-O-B-D-GLUCOPYRANOSIDE AND ETHANOLIC ROOT EXTRACT OF OPERCULINA TURPETHUM AGAINST N- NITROSODIMETHYLAMINE INDUCED HEPATOPATHY IN THE LIVER OF MICE: ULTRASTRUCTURAL AND HISTOLOGICAL EVIDENCES
Keywords:
Hepatic, Operculina turpethum, Scanning Electron Microscopy, CancerAbstract
Objective: Liver is the most important organ in the pivotal role of regulating various physiological processes and several vital functions like metabolism, secretion and storage. Plants are reputed in the indigenous systems of medicine for the treatment of various diseases. Toxicant or drug induced liver injury can be prevented by treating with non toxic hepatoprotective herbs, which can possess membrane stabilizing, hepatoprotective and antioxidant activities. NDMA (N- Nitrosodimethylamine) belongs to nitrosamine compounds which are known hepatic carcinogens.
Methods: The aim of the present investigation was to analyse the effects of NDMA on the morphology of hepatic cells, to determine the reversible effect if any, after providing the treatment with the crude extract and isolated glycoside from the roots of Operculina turpethum. The treatment was given in different groups of Swiss Albino Mice.
Results: Scanning Electron Microscopy and Light microscopical examinations indicated that NDMA treated mice livers (n = 6) displayed severe vascular and endothelial damage compared to control livers (n = 6). Liver sections appeared with inflammatory cellular infiltration, vacuolated hepatocytes, dilated sinusoids, increased number of Kupffer cells, fibrosis, endothelial fenestrations, intercellular spaces and spaces of Disse, and were accompanied by dilatation of bile canaliculi.
Conclusion: These alterations were recovered with the treatment at the dose of 400 mg/kg of crude extract and 50 mg/kg of the isolated compound. Hence, it can be stated that this plant can show significant recovery in NDMA damaged livers.
Downloads
References
Opoku R, Ndlovu IM, Terblanche SE, Hutchings AH. In vivo hepatoprotective effects of Rhoicissus tridentata subsp. cuneifolia, a traditional Zulu medicinal plant, against CCl4-induced acute liver injury in rats. S Afr J of Bot 2007;73(3):372-7.
Abdullaev FI. Plant-derived agents against cancer. In: Gupta SK (ed) Pharmacology and therapeutics in the new millennium. New Delhi: Narosa Puplising House; 2001. p. 345–354.
DeLeve LD, Kaplowitz N. Mechanisms of drug induced liver disease. Gastroenterol clin N Am 1995;24:787-810.
Aruna K, Sivaramakrishnan VM. Plant products protective against cancer. Indian J Exp Biol 1990;26:1008-11.
Moreau RA, Whitaker BD, Hicks KB. Phytosterols, phytostanols, and their conjugates in foods: Structural diversity, quantitative analysis, and health-promoting uses. Prog Lipid Res 2002;41:457–500.
Sharma V, Singh M. Operculina turpethum as a panoramic herbal medicine. Int J Pharm Sci Res 2012;3(1):01-05.
Sharma V, Singh M. Alterations induced by N-Nitrosodimethylamine and ethanolic root extract of Operculina turpethum in serum lipid profile of male albino mice. Asian J Pharm Clin Res 2012;5(3):69-73.
Ding W, Zeng F, Xu L, Chen Y, Wang Y, Wei X. Bioactive dammarane-type saponins from Operculina turpethum. J Nat Products 2011;74(9):1868-74.
IARC. Some N-Nitroso Compounds. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans. Int Agency for Res on Cancer 1978;17:365.
Saprin AN, Piette LH. Spin trapping and its application in the study of lipid peroxidation and free radical production with liver microsomes. Arch Biochem Biophys 1994;180:480-92.
Ahotupa M, Bussacchini GV, Bereziat JC, Camus AM, Bartsch H. Rapid oxidative stress induced by N-nitro-soamines. Biochem Biophys Res Commun 1987;146:1047-54.
Sharma V, Singh M. N-Nitrosodimethylamine as a hazardous chemical toxicant in drinking water. Int Res J Pharm 2012;3(3).
Hamilton, Martin A, Rosemarie CR, Robert VT. Trimmed Spearman-Karber Method for estimating Median Lethal Concentrations in Toxicity Bioassays. Env Sci and Tech 1977;11(7):714-8.
Ahmad R. Operculina turpethum attenuates N-nitroso dimethylamine induced toxic liver injury and clastogenicity in rats. Chem-Biol Int 2009;181:145-53.
Bancroft JD, Stevens A. Theory and Practice of Histology Techniques. 2nd Edn. Churchill Livingstone, Edenburgh, London: Melbourne and New York; 1982. p. 680.
Hayat MA. Principles and Techniques of Electron Microscopy Biological Application. 3rd Edn. CRC Press: Boca Raton FL; 1989. p. 469.
Boyd EM, Bereczky GM. Liver necrosis from paracetamol. Br J Pharmacol 1966;26:606-14.
Schuppan D, Ruehl M, Somasundaram R, Hahn EG. Matrix as a modulator of hepatic fibrogenesis. Semin Liver Dis 2001;21:351-72.
Sauer JM, Waalkes MP, Hooser MP, Kuester RK, McQueen CA, Sipes IG. Suppression of Kupffer cell function prevents cadmium-induced hepatocellular necrosis in the male Sprague-Dawley rat. Toxicology 1997;121:155–64.
Laskin DL, Pilaro AM, Ji S. Potential role of activated macrophages in acetaminophen hepatotoxicity. II. Mechanism of macrophage accumulation and activation. Toxicol Appl Pharmacol 1986;86:216–26.
Salguero PR, Roderfeld M, Hemmann S, Rath T, Atanasova S, Tschuschner A, Gressner OA, Weiskirchen R, Graf J, Roeb E. Activation of hepatic stellate cells is associated with cytokine expression in thioacetamide-induced hepatic fibrosis in mice. Lab Invest 2008;88(11):1192-203.
Bartsch H, Hietanen E, Malaveille C. Carcinogenic nitrosamines: free radical aspects of their action. Free Radic Med Biol 1989;7:637–44.
Harmeet M, Gregory J, John J. Lemasters. Apoptosis and Necrosis in the Liver: A Tale of Two Deaths. Hepatology 2006;43:31-44.