Role of Heme Oxygenase-1 in Acquired Resistance in Glycerol-induced Acute Renal Failure of Rats

Abstract

The purpose of this study was to elucidate the role of renal heme oxygenase (HO)-1 and glutathione (GSH) in acquired resistance in glycerol-induced acute renal failure (ARF) of rats. Prior administration of glycerol conferred resistance to glycerol-induced ARF morphologically as well as functionally (acquired resistance). In glycerol-treated rats, HO-1 mRNA expression determined by reverse transcription-polymerase chain reaction was induced, whereas renal GSH content was significantly decreased. Pretreatment with tinprotoporphyrin, a specific and competitive inhibitor of HO-1 blocked the acquired resistance in glycerol-induced ARF and the increase in level of HO-1 mRNA expression, and restored the level of renal GSH content up to the level similar to that of control. These results suggest that HO-1 is at least in part responsible for the acquired resistance in glycerol-ARF in rats. In addition, the results also raise the intriguing possibility that GSH exhibits direct as well as indirect antioxidative effects through the induction of HO-1.