We investigated whether two naturally-occurring prooxidants, namely, schisandrin B (Sch B) and curcumin, and a synthetic prooxidant, menadione, can invariably elicit cyto/hepatoprotective responses against oxidant-induced injury. Results showed that (−)Sch B (a potent enantiomer of Sch B, 15 μM), curcumin (7.5 μM) and menadione (2 μM) induced a similar extent of reactive oxygen species production in AML12 cells. The relative potencies of cytoprotection in vitro were in a descending order of curcumin>menadione>(−)Sch B, which were parallel to the extent of stimulation in cellular reduced glutathione level. We further examined their hepatoprotection in vivo. Pretreatment with Sch B (800 mg/kg) and curcumin (737 mg/kg), but not menadione (344 mg/kg), protected against CCl4 toxicity, with the degree of protection afforded by Sch B being much larger than that of curcumin. The attenuated hepatoprotection afforded by curcumin may be attributed to its low bioavailability in vivo. This postulation is supported by the findings that intraperitoneal injections of Sch B (400 mg/kg) and curcumin (368 mg/kg) and the long term, low dose treatment with Sch B (20 mg/kg/d×15) and curcumin (18 mg/kg/d×15) induced glutathione antioxidant response and hepatoprotection to similar extents in vivo. The inability of menadione to induce hepatoprotection may be related to its extensive intestinal metabolism and/or hepatotoxicity. Taken together, prooxidants can invariably induce the glutathione antioxidant response and confer cytoprotection in vitro. Whether or not the prooxidant can produce a similar response in vivo would depend on its bioavailability and potential toxic effect.
2012 The Pharmaceutical Society of Japan