Protective Effects of KW-3902, an Adenosine A1-Receptor Antagonist, Against Cisplatin-Induced Apoptosis in Rat Kidney.

Abstract

We histopathologically examined rat kidneys which were obtained 1 hour, 1 day, and 3 days after a single administration of cisplatin (CDDP). Pretreatment with KW-3902 (0.1 mg/kg) reduced an increase in TUNEL-positive tubular cells on day 1 and day 3. On day 1 and thereafter, in the CDDP-treated groups, ultrastructural examination revealed findings characteristic of apoptosis such as nuclear chromatin condensation of the proximal tubular epithelia. Moreover, we determined the effect of KW-3902 on the CDDP content of urine, blood, and kidney in rats. Pretreatment with KW-3902 (0.1 mg/kg) did not affect plasma CDDP concentration or cumulative urinary excretion of CDDP, until 40 min after a bolus injection of CDDP, but induced diuresis, resulting in decreased urinary concentration of CDDP and reduced accumulation of CDDP in the kidney. These results suggest that the protective effect of KW-3902 against CDDP-induced acute renal failure is at least partly attributable to reduced apoptosis of the proximal tubular epithelium, possibly resulting from the reduction of CDDP accumulation in the same place.