Cisplatin nephrotoxicity: site of functional disturbance and correlation to loss of body weight.
We have investigated the effect of an intraperitoneal cisplatin injection (5 mg/kg body weight) into male Wistar rats on: (1) body weight; (2) proximal tubular transport of D-glucose and sulfate across the luminal 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-dithiocarbamate (NaG), diethyldithiocarbamate, mercaptosuccinate (MS), probenecid, and glycine on parameters 1, 4 and 5. Five days after intraperitoneal application of cisplatin the following effects were observed: (1) body weight was reduced on average by 11% as compared to a 12% increase in control animals; (2) luminal sulfate and D-glucose transport was inhibited correlating with the degree of weight loss; (3) contraluminal PAH transport was also decreased in correlation to the loss of body weight, while contraluminal sulfate transport was not inhibited by cisplatin; (4) inulin excretion was reduced by 45%, the pattern for protection was the same as for the prevention of weight loss; (5) sulfofluorescein (SF) excretion in the urine was reduced by 43%, and (6) accumulation of SF into cortical tissue was augmented. Protecting substances prevented or mitigated weight loss, fall of urinary inulin and SF excretion as well as SF accumulation in cortical tissue with a similar pattern: N-glucamine-dithiocarbamate > mercaptosuccinate approximately probenecid approximately glycine. The data indicate: (1) that luminal (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 indicates that a simple index might be useful to monitor the cytotoxic status of an individual.
Ammer
U
U
Max-Planck-Institut für Biophysik, Frankfurt, BRD.
Natochin
Y u
Yu
David
C
C
Rumrich
G
G
Ullrich
K J
KJ
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D005452:Fluoresceins; D005947:Glucose / Q000378:metabolism; D007444:Inulin; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects*; D010130:p-Aminohippuric Acid
D005452:Fluoresceins; D013431:Sulfates; D007444:Inulin; D005947:Glucose; D002945:Cisplatin; D010130:p-Aminohippuric Acid