Tanshinone IIA protects rat primary hepatocytes against carbon tetrachloride toxicity via inhibiting mitochondria permeability transition

Tanshinone IIA (Tan IIA), one of the key components of Salvia milthorrhiza Bunge (Lamiaceae), is used to treat liver disease. The present study was carried out to investigate the possible mechanisms involved in the hepatoprotective effects of Tan IIA on carbon tetrachloride (CCl(4))-induced hepatocyte toxicity. In cultures treated with 1 or 2 microM CCl(4), Tan IIA (10-75 microM) significantly increased hepatocyte survival rates. However, only at a concentration of 75 microM could Tan IIA partially reverse the CCl(4) (3 microM)-induced decrease of survival rate (34 +/- 3% vs. 18 +/- 3%, n = 8, p < 0.01). In isolated mitochondria energized with succinate, Tan IIA could inhibit the large swelling effect induced by CCl(4) (1 and 2 microM). Base on these results, Tan IIA could protect rat primary cultured hepatocytes from CCl(4)-induced toxicity partially by the inhibitory effect on the opening of mitochondrial permeability transition (MPT).