Protection effects of procaine on oxidative stress and toxicities of renal cortical slices from rats caused by cisplatin in vitro.
Incubation of rat renal cortical slices with 2 mM cisplatin (CDDP) at 37 degrees C for different periods of time (15-180 min) increased malondialdehyde (MDA) formation, decreased intracellular glutathione (GSH), and inhibited gluconeogenesis in the slices. CDDP-induced MDA formation increased by 53% after 180 min of incubation and GSH decreased by 35% after 60 min of incubation. Both depletion of GSH and inhibition of gluconeogenesis preceded MDA formation. Procaine (2 mM) completely inhibited CDDP-induced lipid peroxidation without affecting depletion of GSH, but even potentiated gluconeogenesis inhibition, while 2 mM dithiothreitol (DTT) largely reversed all of these biochemical indices. After 240 min of incubation, 2 mM CDDP produced marked cytotoxicities, characterized by an increase in leakage of alkaline phosphatase (ALP) (132%), lactate dehydrogenase (LDH) (115%) and N-acetyl-beta-glucosaminidase (NAG) (157%), decrease in intracellular K+ (64%), and change in total water contents in the slices. Procaine (2 mM) showed protection against CDDP-induced cytotoxicities to a certain extent. These results suggest that depletion of GSH might be a determinant step in the oxidative stress and subsequent cytotoxicity, and that procaine is a powerful antioxidant and would be a promising drug for ameliorating some of the adverse effects of CDDP.
Zhang
J G
JG
Department of Toxicology, Dalian Medical College, Republic of China.
Zhong
L F
LF
Zhang
M
M
Xia
Y X
YX
D000818:Animals; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005943:Gluconeogenesis / Q000187:drug effects; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction; D010984:Platinum / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011343:Procaine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism
D013438:Sulfhydryl Compounds; D010984:Platinum; D008315:Malondialdehyde; D011343:Procaine; D012964:Sodium; D002945:Cisplatin; D011188:Potassium