Protection effects of procaine on oxidative stress and toxicities of renal cortical slices from rats caused by cisplatin in vitro

Abstract

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.

Effect of <i>L</i>-Histidinol on Cisplatin Nephrotoxicity in the Rat

“…Previous investigations have suggest ed that CDDP-induced nephrotoxicity is related to oxida tive stress and that lipid peroxidation is one of the mecha nisms [22,23], In the present study, CDDP induced a sig nificant increase in both renal glutathione and lipid per oxide levels, 5 days after administration. This finding is compatible with the earlier work of others [24,25].…”

Role of Ursodeoxycholic Acid in Prevention of Methotrexate-induced Liver Toxicity

“…Recently, hydrogen peroxide molecules were reported to act as mediators both in the therapeutic and toxic effects of some antineoplastic agents including MTX [35]. Oxidative stress and lipid peroxidation mediated by oxygen free radicals has been implicated as a common link between chronic liver damage and hepatic fibrosis.…”

The Effect of Antioxidant Caffeic Acid Phenethyl Ester (Cape) on Some Enzyme Activities in Cisplatin-Induced Neurotoxicity in Rats

“…NaHCO 3 served as control, dissolved with distilled water was given intraperitoneally (as equal volume of CAPE) 24 hours prior to the saline injection, followed by once a day at the same dose until sacrifice. Group II (CDDP): The animals (n: 9) received intraperitoneal injection of CDDP (cisplatinum Ebewe, 0.5 mg/ml) at a dose of 7 mg/kg body wt and were sacrificed 5 days after CDDP injection (22). Brains were obtained for the various measurements.…”