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.
Fawcett
J P
JP
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Schiller
B
B
Jiang
R
R
Moran
J
J
Walker
R J
RJ
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D005978:Glutathione / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D011692:Puromycin Aminonucleoside / Q000633:toxicity*; D011761:Pyrrolidonecarboxylic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D053778:Thiazolidines; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D013844:Thiazoles; D053778:Thiazolidines; D017392:Thiobarbituric Acid Reactive Substances; D011692:Puromycin Aminonucleoside; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid