Abstract
Incubation of rat renal cortical slices with 2 mM cisplatin (CDDP) at 37‡ 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-Β-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.
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Zhang, J.G., Zhong, L.F., Zhang, M. et al. Protection effects of procaine on oxidative stress and toxicities of renal cortical slices from rats caused by cisplatin in vitro. Arch Toxicol 66, 354–358 (1992). https://doi.org/10.1007/BF01973631
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DOI: https://doi.org/10.1007/BF01973631