Imbalance of the antioxidative system by plumbagin and Plumbago indica L. extract induces hepatotoxicity in mice.
OBJECTIVE
Plumbago indica (PI) 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 PI extract (PI) on hepatic histomorphology and antioxidative system in mice.


METHODS
Adult male intelligent character recognition 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, 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.


CONCLUSIONS
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.
Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology, Khon Kaen University.
Nadta
N
Sukkasem
Department of Preclinic, Faculty of Medicine, Mahasarakham University, Mahasarakham 44000 Thailand.
Waranya
W
Chatuphonprasert
Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology, Khon Kaen University.
Nitima
N
Tatiya-Aphiradee
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002 Thailand.
Kanokwan
K
Jarukamjorn
Antioxidative system; Plumbago indica; glutathione; hepatotoxicity; plumbagin; transaminase