Role of renal heme oxygenase-1 and glutathione in acquired resistance to glycerol-induced acute renal failure in rats

The purpose of this study is to elucidate the role of renal heme oxygenase (HO)-1 and glutathione (GSH) in acquired resistance to glycerol-induced acu te renal failure (ARF) in rats. Prior administration of glycerol conferred resistance to glycerol-induced ARF, as assessed morphologically as well as functionally (acquired resistance). HO-1 mRNA expression was induced in gly cerol-treated rats, while the renal GSH content was significantly decreased . Pretreatment with tin-protoporphyrin, a specific and competitive inhibito r of HO-1, blocked the increase in HO-1 mRNA expression, abolished the glyc erol-induced protection against glycerol-induced ARF, and restored the rena l GSH content to the level found in controls. These results suggest that HO -1 is responsible, at least in part, for the glycerol-induced acquired resi stance to glycerol-induced ARF in rats. In addition, the results also raise the intriguing possibility that GSH exhibits direct as well as indirect an tioxidative effects through the production of bilirubin by the induction of HO-1.