Induction of Heme Oxygenase by Phorone (Diisopropylidene Acetone), a Potent Glutathione-Depleting Agent, Is Not Mediated by Glutathione Depletion and Lipid Peroxidation.

Abstract

Oxidative stress is suggested to be involved in the induction of tissue microsomal heme oxygenase (HO). Phorone (diisopropylidene acetone) is a glutathione (GSH)-depleting agent as well as a potent inducer of HO. In this study, phorone and another GSH-depleting agent, buthionine sulfoximine (BSO), were compared in rats given a normal (7 IU /100 g diet) or high (100 IU/100 g diet) level of dietary vitamin E (VE) to determine whether HO induction is mediated through GSH depletion and/or lipid peroxidation. In Experiment 1, single (250 mg/kg B.W.) and three consecutive doses (250mg/kg B.W./day) of phorone to animals given normal dietary VE comparably decreased the liver GSH contents, but the liver microsomal HO was induced in a dose-dependent manner. Liver chemiluminescence intensity also increased in response to the dose level of phorone, suggesting an enhanced liver lipid peroxidation stimulated by phorone administration. In Experiment 2, phorone (250 mg/kg B.W./day) or BSO (1 mmol/kg B.W./day) was administered intermittently 4 times to animals given a normal or high level of dietary VE. Administration of phorone and BSO significantly decreased the GSH contents both in the liver and kidney, but no effect of high dietary VE on the contents was observed. HO was induced significantly in both the liver and kidney following phorone treatment, but not by BSO. High dietary VE also did not affect the phorone-induced HO activity. Phorone administration significantly enhanced the liver chemiluminescence intensity, but it was suppressed to the control level by high dietary VE. BSO administration did not promote lipid peroxidation in the liver. In the kidney, neither phorone nor BSO stimulated lipid peroxidation. From these results, we presume that induction of HO by phorone in the liver and kidney is not mediated by GSH depletion and lipid peroxidation.