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Imbalance of the antioxidative system by plumbagin and Plumbago indica L. extract induces hepatotoxicity in mice

Nadta Sukkasem, Waranya Chatuphonprasert, Nitima Tatiya-aphiradee, Kanokwan Jarukamjorn.




Abstract

Background/Aim: Plumbago indica L. and its active constituent, plumbagin, has been traditionally claimed for several pharmacological activities, however, there is little information regarding their toxicity. The present study aims to examine the effects of plumbagin and P. indica extract (PI) on hepatic histomorphology and antioxidative system in mice. Materials and Methods: Adult male ICR mice were intragastrically administered plumbagin (1, 5, and 15 mg/kg/day) or PI (20, 200, and 1,000 mg/kg/day) consecutively for 14 days. Hepatic histomorphology was examined. Plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, and hepatic lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, and the ratio of reduced to oxidized glutathione (GSH/GSSG) were determined. Results: Plumbagin and PI concentration-dependently induced hepatic injury based on histopathological changes via imbalance of antioxidative system. Plumbagin and PI significantly increased plasma ALT and AST levels, hepatic lipid peroxidation, and GPx activity but significantly decreased hepatic SOD and CAT activities. The GSH/GSSG ratio was significantly reduced by plumbagin. Conclusion: Plumbagin and PI caused hepatotoxic effects in the mice by unbalancing of the redox defense system. Therefore, plumbagin and PI containing supplements should be used cautiously, especially when consumed in high quantities or for long periods.

Key words: antioxidative system, glutathione, hepatotoxicity, plumbagin, Plumbago indica, transaminase






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