Direct amifostine effect on renal tubule cells in rats

Clinical trials indicate that amifostine offers protection against cisplati n-induced nephrotoxicity, It is unclear whether a direct pharmacological ef fect on renal tubular cells is involved. We investigated the effect of amif ostine pretreatment on the tubular apparatus and evaluated its nephroprotec tive potential. A total of 32 rats were treated by i.p. administration of 0 .9% saline solution (group 1), 5 mg/kg cisplatin (group 2), 25 mg/kg amifos tine (group 3), and 25 mg/kg amifostine followed by 5 mg/kg cisplatin (grou p 4) after 30 min. We recorded elevation of N-acetyl-beta-D-glucosaminidase (NAG) in 24 h pooled urine as a specific marker for tubular lesions, renal leakage of magnesium as an unspecific nephrotoxicity marker, and survival over a 10-day observation period, A significant (P < 0.002) increase in uri nary NAG after treatment was documented only in cisplatin-treated group 2 [ day 2 (mean +/- SE), 9.3 +/- 2.1 units/gram creatinine; day 4, 70.6 +/- 16 units/gram creatinine; normalization at day 8], Treatment with amifostine b efore cisplatin administration resulted in a slight urinary NAG leakage (da y 2, 2.8 +/- 1,8 units/gram creatinine; day 4, 13.8 +/- 13 units/gram creat inine; normalization at day 6). No increase in urinary enzyme levels was se en in the other groups, and there were no significant differences in urinar y magnesium between all groups. Pour of eight rats in the cisplatin-treated group and one of eight rats in the amifostine plus cisplatin-treated group died.