CISPLATIN NEPHROTOXICITY - SITE OF FUNCTIONAL DISTURBANCE AND CORRELATION TO LOSS OF BODY-WEIGHT

We have investigated the effect of an intraperitoneal cisplatin inject ion (5 mg/kg body weight) into male Wistar rats on: (1) body weight; ( 2) proximal tubular transport of D-glucose and sulfate across the lumi nal membrane; (3) transport of p-aminohippuric acid (PAH) and sulfate across the contraluminal membrane; (4) urinary excretion of inulin; (5 ) urinary excretion and tissue accumulation of sulfofluorescein, and ( 6) effect of the 'protecting substances', N-Methyl-D-glucamine-dithioc arbamate (NaG), diethyldithiocarbamate, mercaptosuccinate (MS), proben ecid, and glycine on parameters 1, 4 and 5. Five days after intraperit oneal application of cisplatin the following effects were observed: (1 ) body weight was reduced on average by 11% as compared to a 12% incre ase in control animals; (2) luminal sulfate and D-glucose transport wa s inhibited correlating with the degree of weight loss; (3) contralumi nal PAH transport was also decreased in correlation to the loss of bod y weight, while contraluminal sulfate transport was not inhibited by c isplatin; (4) inulin excretion was reduced by 45%, the pattern for pro tection was the same as for the prevention of weight loss; (5) sulfofl uorescein (SF) excretion in the urine was reduced by 43%, and (6) accu mulation of SF into cortical tissue was augmented. Protecting substanc es prevented or mitigated weight loss, fall of urinary inulin and SF e xcretion as well as SF accumulation in cortical tissue with a similar pattern: N-glucamine-dithiocarbamate > mercaptosuccinate almost-equal- to probenecid almost-equal-to glycine. The data indicate: (1) that lum inal (glucose and sulfate) and contraluminal (PAH) transport processes are affected by cisplatin; (2) that contraluminal transport (sulfate) can be unaffected or less affected than luminal transport processes ( SF); (3) our method (SF) gives the possibility to monitor the balance between luminal and contraluminal transport steps in vivo; and (4) the correlation of body weight loss with decay of certain renal transport functions and their prevention with similar protecting patterns indic ates that a simple index might be useful to monitor the cytotoxic stat us of an individual.