EVALUATION OF HEPATOPROTECTIVE ACTIVITY OF FICUS RELIGIOSA ON RATS AGAINST CCL4 AND PARACETAMOL INDUCED HEPATOTOXICITY
Discussion & Conclusion
Liver is the main organ responsible for the biosynthesis, uptake & degradation of protein and enzyme. Liver function may therefore be reflected to some extent on the level and/ or the activities of these biochemical compound. The immune system is increasingly found to be involved in the development of several chronic illness, for which allopathic medicines has provided limited tools for treatment & especially prevention.
It is well established that CCl4 induces hepatotoxicity by metabolic activation; therefore it selectively causes toxicity in liver cells maintaining semi normal metabolic function. CCl4 is biotransformed by cytochrome P450 system in the endoplasmic reticulum to produce trichloromethyl free radical (CCl3). Trichloromethyl free radical when combined with cellular lipids and proteins in the presence of oxygen form trichloromethylperoxyl radical, which may attack lipids on the membrane of endoplasmic reticulum faster than trichloromethyl free radical. Thus, trichloromethylperoxyl free radical leads to elicit lipid peroxidation. The destruction of Ca2+ homeostasis, finally results in cell death. Hepatoprotective activity of any drug is the ability of its constituents to inhibit the aromatase activity of cytochrome P450 thereby favoring liver regeneration. In the present study it was observed that the administration of CCl4 decreased the levels of proteins and increased the levels of serum marker enzymes significantly (P<0.001) which is an evidence of existence of liver toxicity when compared to normal animals.
Paracetamol is a commonly and widely used analgesic antipyretic agent. Hepatotoxic doses of paracetamol deplete the normal levels of hepatic glutathione. The hepatic cytochrome P450 enzyme system metabolizes paracetamol, forming a minor yet significant alkylating metabolite known as NAPQI (N-acetyl-p-benzo-quinone imine). NAPQI is then irreversibly conjugated with the sulfhydryl groups of glutathione. NAPQI is primarily responsible for the toxic effects of paracetamol.
Production of NAPQI is primarily due to, two isoenzymes of cytochrome P450: CYP2E1 and CYP1A2. The P450 gene is highly polymorphic, however, and individual differences in paracetamol toxicity were believed to be due to a third isoenzyme, CYP2D6. CYP2D6 metabolises paracetamol into NAPQI to a lesser extent than other P450 enzymes, its activity may contribute to paracetamol toxicity in extensive and ultrarapid metabolisers, and when paracetamol is taken at very large doses. In the liver, the cytochrome P450 enzymes CYP2E1 and CYP3A4 were primarily responsible for the conversion of paracetamol to NAPQI which undergoes conjugation with glutathione. Conjugation depletes glutathione, a natural antioxidant. This in combination with direct cellular injury by NAPQI, leads to cell damage and death. Excess production of paracetamol metabolite causes the initial hepatic damage and subsequent activation of inflammatory mediator TNF-α which in turn contribute to tissue necrosis.
In the present study, it was seen that administered of ccl4 & paracetamol elevates the level of serum marker enzymes SGPT, SGOT, ethanolic extract of ficus religiosa & silymarin treated group exhibited lower level of SGPT, SGOT level in ccl4 & paracetamol treated group. The stabilization of serum SGPT, SGOT levels by ficus religiosa is a indication of the improvement of the functional status of liver cells The biochemical examination clearly level that the hepatic cells are normal in ethanolic extract of ficus religiosa treated group (200mg/kg p.o.) in contrast group which received CCl4 & paracetamol. Thus ethanolic extract of ficus religiosa can be considered to be an effective hepatoprotective in nature, as it normalize the damage caused by CCl4 to hepatic function. Thus the ethanolic extract of ficus religiosa seems to possess hepatoprotective activity.
The authors are thankful and would like to express their deep gratitude to Prof. P.K. Tiwari, Dr. H S Gour Central University Sagar, for authentication of plant. Authors like to acknowledge Miss Reva Pandav from Bhopal Awasthi Diagnostic Centre Bhopal for providing sample of silymarin & Dr.H.S.Chandel from Truba Institute of Pharmacy Bhopal for availing the laboratory facilities during the course of investigation.
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