A COMPARATIVE-STUDY OF URANYL-NITRATE AND CISPLATIN-INDUCED RENAL-FAILURE IN RAT

Renal dysfunction can have substantial effects on the pharmacokinetics and pharmacodynamics of drugs. A wide variety of animal models have b een developed in an attempt to mimic conditions seen in human renal fa ilure. In reality, no single animal model would be completely satisfac tory because the etiology and development of renal failure are diverse . During recent years injection of uranyl nitrate has been found to be the most effective and easiest method to produce renal dysfunction in laboratory animals. Changes over the last 10 years in government regu lations on the production and use of radioactive substances make the c ompound less available. There is, therefore, a need for a more accessi ble compound comparable to uranyl nitrate as an inducer of renal failu re. The present study compares the effects of another known nephrotoxi n, cisplatin, with uranyl nitrate in the rat. Cisplatin was chosen bec ause of its ability to produce kidney damage and its identical site an d mechanism of action on the kidneys as uranyl nitrate. In the present study, rats were given different i.v. doses of uranyl nitrate or cisp latin dissolved in 0.9% of saline solution. The effects of nephrotoxin s were evaluated on the basis of changes in body weight, creatinine an d blood urea nitrogen (BUN) concentrations. It was found that the degr ee of renal damage produced by uranyl nitrate and cisplatin is a funct ion of the administered dose. With increasing dose there is evidence o f more severe kidney damage, as measured by substantially increased pl asma concentrations of creatinine and BUN. The time required to return to normal creatinine and BUN concentrations was also a function of do se. Furthermore, plasma alanine aminotransferase (ALT) activity was me asured as an index of hepatocellular damage. The ALT test showed that a single dose does not affect the liver function. From dose-response c urves a dose of 4 mg/kg body weight of uranyl nitrate or cisplatin was chosen to produce acute renal failure in animals for pharmacokinetic study of barbital Barbital (100 mg/kg) was administered on the fifth d ay (the day of maximum renal dysfunction) to uranyl nitrate, cisplatin -treated and control rats. The elimination rate constant (k), eliminat ion half life (t(1/2)), volume of distribution at steady state (V-ss), total (CL(t)) and renal clearance (CL(r)) were significantly differen t in treated groups of rats from control, however no such difference w as detected between uranyl nitrate and cisplatin-treated group of rats . In short, cisplatin is comparable to uranyl nitrate in producing ren al failure in the rat and can be considered a suitable alternative.