A comparative study of uranyl nitrate and cisplatin-induced renal failure in rat

Abstract

Renal dysfunction can have substantial effects on the pharmacokinetics and pharmacodynamics of drugs. A wide variety of animal models have been developed in an attempt to mimic conditions seen in human renal failure. In reality, no single animal model would be completely satisfactory 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 regulations on the production and use of radioactive substances make the compound less available. There is, therefore, a need for a more accessible compound comparable to uranyl nitrate as an inducer of renal failure. The present study compares the effects of another known nephrotoxin, cisplatin, with uranyl nitrate in the rat. Cisplatin was chosen because of its ability to produce kidney damage and its identical site and mechanism of action on the kidneys as uranyl nitrate. In the present study, rats were given different i.v. doses of uranyl nitrate or cisplatin dissolved in 0.9% of saline solution. The effects of nephrotoxins were evaluated on the basis of changes in body weight, creatinine and blood urea nitrogen (BUN) concentrations. It was found that the degree of renal damage produced by uranyl nitrate and cisplatin is a function of the administered dose. With increasing dose there is evidence of more severe kidney damage, as measured by substantially increased plasma concentrations of creatinine and BUN. The time required to return to normal creatinine and BUN concentrations was also a function of dose. Furthermore, plasma alanine aminotransferase (ALT) activity was measured as an index of hepatocellular damage. The ALT test showed that a single dose does not affect the liver function. From dose-response curves 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 day (the day of maximum renal dysfunction) to uranyl nitrate, cisplatin-treated and control rats. The elimination rate constant (k), elimination half life (t1/2), volume of distribution at steady state (Vss), total (CLt) and renal clearance (CLr) were significantly different in treated groups of rats from control, however no such difference was detected between uranyl nitrate and cisplatin-treated group of rats. In short, cisplatin is comparable to uranyl nitrate in producing renal failure in the rat and can be considered a suitable alternative.

Protective Effect of Montelukast Which Is Cysteinyl-Leukotriene Receptor Antagonist on Gentamicin-Induced Nephrotoxicity and Oxidative Damage in Rat Kidney

“…A number of environmental variables including certain drugs influence these functions. [1][2][3] Aminoglycoside antibiotics, including gentamicin (GEN), are widely used in the treatment of gram-negative infections. A major complication of these drugs is nephrotoxicity, and it has been estimated that approximately 10-20% of the cases were treated with aminoglycoside therapy.…”

Administration of gentamicin induced hematobiochemical and renal morphological alterations in Swiss albino mice

“…It plays an important role to remove foreign substances from the blood. Many environmental contaminants and chemical (Mahmood and Waters, 1994).…”

Assessment of ameliorative effects of aqueous extracts of Moringa oleifera on acetaminophen -induced nephrotoxicity in rats

“…Moreover, it plays a vital role in regulating various physiological processes in the body as water and electrolyte homeostasis, maintenance of plasma osmolarity, acid-base balance, and the production and secretion of hormones [3,4]. Due to the fact that, drug elimination was occurs mainly via the kidneys and thus several previous reports suggested the toxic effects of environmental contaminants including drugs might response to alter the functions of the kidney [5,6]. Nevertheless, as kidney function declines, each of the kidney's functions is affected and/or decline at different rates, including clearance of drugs and their metabolites.…”