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 this study was to determine if L-2-oxothiazolidine-4-carboxylic acid (procysteine) would protect rats against PAN-induced nephrotoxicity. Male Sprague-Dawley rats were treated with procysteine (16 mg/100 g body weight i.p.) 24 h and 30 min prior to receiving a single injection of PAN (15 mg/100 g body weight i.v.) followed by procysteine in the drinking water (4 g/l), Control rats received procysteine alone (intraperitoneally and in drinking water) or PAN alone and then plain water. Proteinuria was not significantly different between PAN/procysteine and PAN groups, reaching a maximum at day 14 and persisting at day 28. Lipid peroxidation was more severe in PAN/procysteine rats reaching a maximum 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 proteinuria 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 and PAN/procysteine rats. Focal glomerulosclerosis (FGS) was worse at day 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 source of reducing equivalents does not protect against renal lipid peroxidation and FGS In this model. On the contrary, PAN/procysteine rats developed significantly more FGS through yet unknown mechanisms.