SUPPLEMENTATION WITH L-2-OXOTHIAZOLIDINE-4-CARBOXYLIC ACID, A CYSTEINE PRECURSOR, DOES NOT PROTECT AGAINST LIPID-PEROXIDATION IN PUROMYCIN AMINONUCLEOSIDE-INDUCED NEPHROPATHY

Lipid peroxidation in the kidney has been shown to precede proteinuria in puromycin aminonucleoside (PAN)-induced nephropathy. The aim of th is study was to determine if L-2-oxothiazolidine-4-carboxylic acid (pr ocysteine) would protect rats against PAN-induced nephrotoxicity. Male Sprague-Dawley rats were treated with procysteine (16 mg/100 g body w eight i.p.) 24 h and 30 min prior to receiving a single injection of P AN (15 mg/100 g body weight i.v.) followed by procysteine in the drink ing water (4 g/l), Control rats received procysteine alone (intraperit oneally and in drinking water) or PAN alone and then plain water. Prot einuria was not significantly different between PAN/procysteine and PA N groups, reaching a maximum at day 14 and persisting at day 28. Lipid peroxidation was more severe in PAN/procysteine rats reaching a maxim um at day 3 (253 +/- 30 ng/mg protein) compared to day 5 in PAN rats ( 196 +/- 20 ng/mg protein), Procysteine alone did not modulate proteinu ria over 28 days or lipid peroxidation over 7 days. GSH levels over 7 days were not elevated by procysteine and were virtually zero in PAN a nd PAN/procysteine rats. Focal glomerulosclerosis (FGS) was worse at d ay 28 in PAN/procysteine rats than in PAN rats (39 +/- 8.2 vs. 23 +/- 4.5%; p < 0.05). This study shows that procysteine as a potential sour ce of reducing equivalents does not protect against renal lipid peroxi dation and FGS In this model. On the contrary, PAN/procysteine rats de veloped significantly more FGS through yet unknown mechanisms.