Dihydroisotanshinone I Protects Against Menadione-Induced Toxicity in a Primary Culture of Rat Hepatocytes

Abstract

Dihydroisotanshinone I is a phenanthrenequinone derivative isolated from the roots of Salvia trijuga Diels. The present study demonstrated the hepatoprotective effect of dihydroisotanshinone I against menadione-induced cytotoxicity in a primary culture of rat hepatocytes. Pretreating the cells with dihydroisotanshinone I at concentrations ranging from 2.5 μM to 20 μM for 24 hours caused dose-dependent protection against hepatotoxicity induced by menadione. Intracellular glutathione level and activity of DT-diaphorase have been suggested to play important roles in menadione-induced cytotoxicity. However, treating the hepatocytes with 20 μM dihydroisotanshinone I for 24 hours did not cause a significant change in glutathione level and DT-diaphorase activity. On the contrary, adding dihydroisotanshinone I to freshly isolated hepatocytes at concentrations between 50 nM to 200 nM inhibited NADH-induced superoxide production dose-dependently as indicated by the decrease of lucigenin-amplified chemiluminescence. In addition, dihydroisotanshinone I at concentrations ranging from 5 μM to 20 μM inhibited tert-butyl hydroperoxide-induced lipid peroxidation dose-dependently in isolated hepatocytes as indicated by the level of malondialdehyde. These results suggest that the protective action of dihydroisotanshinone I against menadione-induced hepatotoxicity is attributed to its antioxidant properties including the free radical scavenging activity and inhibition of lipid peroxidation.

Abbreviations

DTD:DT-diaphorase

GSH:glutathione

LDH:lactate dehydrogenase

MDA:malondialdehyde

MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

TBHP:tert-butyl hydroperoxide

Salvia trijuga - Lamiaceae - dihydroisotanshinone I - menadione liver damage - free radical scavenger - lipid peroxidation

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