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Propolis protects CYP 2E1 enzymatic activity and oxidative stress induced by carbon tetrachloride

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Induction of CYP 2E1 by carbon tetrachloride (CCl4) is one of the central pathways by which CCl4 generates oxidative stress in hepatocytes. Experimental liver injury was induced in rats by CCl4 to determine toxicological actions on CYP 2E1 by microsomal drug metabolizing enzymes. In this report, ethanolic extract of propolis at a dose of 200 mg/kg (po) was used after 24 h of toxicant administration to validate its protective potential. Intraperitoneal injection of CCl4 (1.5 ml/kg) induced hepatotoxicity after 24 h of its administration that was associated with elevated malonyldialdehyde (index of lipid peroxidation), lactate dehydrogenase and γ-glutamyl transpeptidase release (index of a cytotoxic effect). Hepatic microsomal drug metabolizing enzymes of CYP 2E1 showed sharp depletion as assessed by estimating aniline hydroxylase and amidopyrine N-demethylase activity after CCl4 exposure. Toxic effect of CCl4 was evident on CYP 2E1 activity by increased hexobarbitone induced sleep time and bromosulphalein retention. Propolis extract showed significant improvement in the activity of both enzymes and suppressed toxicant induced increase in sleep time and bromosulphalein retention. Choleretic activity of liver did not show any sign of toxicity after propolis treatment at a dose of 200 mg/kg (id). Histopathological evaluation of the liver revealed that propolis reduced the incidence of liver lesions including hepatocyte swelling and lymphocytic infiltrations induced by CCl4. Electron microscopic observations also showed improvement in ultrastructure of liver and substantiated recovery in biochemical parameters. Protective activity of propolis at 200 mg/kg dose was statistically compared with positive control silymarin (50 mg/kg, po), a known hepatoprotective drug seems to be better in preventing hepatic CYP 2E1 activity deviated by CCl4. These results lead us to speculate that propolis may play hepatoprotective role via improved CYP 2E1 activity and reduced oxidative stress in living system.

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Acknowledgements

Authors are thankful to Prof. O.P. Agrawal for providing crude propolis for experimental work; Dr. P.K. Tiwari for photomicrographic equipment and All India Institute of Medical Sciences, New Delhi for EM facility; Jiwaji university, Gwalior, India and Regional Research Laboratory, Jammu, India for providing laboratory facility. University Grants Commission, New Delhi, India (F-3-45/1999, SR-II) and Madhya Pradesh Council of Science and Technology, Bhopal, India are also acknowledged for financial assistance.

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  1. School of Studies in Zoology, Jiwaji University, Gwalior, 474011, MP, India

    Monika Bhadauria, Satendra Kumar Nirala & Sangeeta Shukla

  2. National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, 730000, P.R. China

    Monika Bhadauria

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  1. Monika Bhadauria
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Correspondence to Monika Bhadauria.

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Bhadauria, M., Nirala, S.K. & Shukla, S. Propolis protects CYP 2E1 enzymatic activity and oxidative stress induced by carbon tetrachloride. Mol Cell Biochem 302, 215–224 (2007). https://doi.org/10.1007/s11010-007-9443-4

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