ONTOGENIC CHANGES IN THE NEPHROTOXICITY OF CHROMATE CORRELATE WITH THE GLUTATHIONE OXIDOREDUCTION SYSTEM

The role of GSH concentration and GSSG reductase activity in age diffe rences in chromate nephrotoxicity was investigated. Young and adult ra ts were injected with 2 and 1 mg sodium chromate/100 g body weight (BW ), respectively, which led to equal Cr concentrations in renal tissue. Cr nephrotoxicity was lower in young than in adult rats. It was shown that from 30 minutes after the chromate injection GSSG reductase acti vity in renal tissue was increased in adult but decreased in young rat s by the chromate. GSSG reductase activity was increased in young rats by pretreatment with phenobarbital. The consequence was an enhancemen t of chromate nephrotoxicity as shown by proteinuria. Renal GSH concen tration is lower in young rats and limiting for chromate reduction in vitro in these animals. Therefore, GSH concentration was increased by pretreatment with N-acetylcysteine, which enhanced chromate nephrotoxi city significantly. These results reflect the important role of the GS H oxidoreduction system in chromate nephrotoxicity and its relationshi p to age differences.