Effect of the lipid peroxide reaction caused by repeated cold stress on cisplatin-induced nephrotoxicity

Abstract

The peroxide reaction in mouse kidney was examined in order to determine the relationship between the lipid peroxide reaction caused by SART (specific alternation of rhythm in temperature) stress and that caused by drug administration. After exerting SART stress for one wk on 6-wk-old male ddY mice (stress group), the peroxide reaction generated by the administration of a single dose of cis-diamminedichloroplatinum (cisplatin: CDDP, 10 mg/kg, i.p.) into SART-stressed mice (stress + CDDP group) was compared with the reaction of CDDP-administered nonstressed mice (CDDP group), saline-administered nonstressed mice (saline group), and saline-administered SART-stressed mice (stress + saline group). Lipid peroxidation in the kidneys was significantly higher in the stress group upon cessation of stress exertion than in the normal group. However, no significant difference in the lipid peroxide level after administration of CDDP was observed between the CDDP groups. The renal glutathione levels were significantly different between the CDDP groups and the saline administered groups. These results indicate that the peroxide reaction is generated in the kidneys by stress, but stress has no effect on the peroxide damage caused by CDDP administration. However, the contribution of stress to renal function impairment requires further evaluation.

Possible Involvement of Oxidative Stress in Cisplatin-Induced Apoptosis in LLC-PK1 Cells

“…It has been demonstrated that wild-type p53 is required for c-Mycinduced apoptosis (Hermeking & Eick, 1994); however, p53-independent mechanisms have also been reported (Sakamuro et al, 1995). Cisplatin-induced nephrotoxicity has been attributed to oxidative stress (Fukuoka et al, 1998;Somani et al, 1995;Namikawa et al, 1998;Meyer & Madias, 1994;Zhang et al, 1992), associated with an increase in lipid peroxides and inhibition of renal antioxidant system (Hannemann & Baumann, 1988;Somani et al, 1995;Salahudeen et al, 1998;. The present study was undertaken to (1) investigate if cisplatin, which also produces oxidative stress, induces apoptosis in LLC-PK1 cells and (2) investigate the involvement of caspases in this event.…”