We investigated the pathobiological course of uranyl nitrate (UN) induced polyuric acute tubular necrosis (ATN) in male Sprague Dawley rats. UN (5mg/kg 15mg/kg and 3Omg/kg) in 5% NaHCO3 induced weight loss, polydipsia, and polyuria 24 hrs after injection when compared to the controls which were treated with 5% NaHCO3 only. Twenty four hours following the injection of UN, serum creatinine and blood urea nitrogen levels had increased. These changes continued for at least 72 hours, although the concentration of uranium had decreased. Light microscopic studies conducted 24 hours after injection, revealed partial degeneration and necrosis of the proximal tubules and many casts m the distal convoluted tubules. These changes progressed for 72 hours. Despite this tubular damage, the glomeruli were relatively intact. 5 days after injection, the epithelial cells lining the proximal tubules displayed regenerative activities; these findings were more prominent after 10 days. Through electron microscopic examination, we observed the destruction of mitochondria in the proximal tubular cells, a possible cause of polyuria. Ten days post injection regenerative activities in the proximal tubular cells showed that the maturation of intracellular organelles followed the proliferation of the premature cells.
Animal ; Kidney Failure, Acute/chemically induced* ; Kidney Function Tests ; Kidney Tubular Necrosis, Acute/chemically induced* ; Male ; Rats ; Rats, Inbred Strains ; Uranium/pharmacology* ; Uranyl Nitrate/pharmacology*

Pharmacokinetics of cefotaxime (50mg/kg, i.m.) were studied in both healthy and kidney damaged female black Bengal goats. Uranyl nitrate (0.75mg/kg) was administered intravenously, once daily for five consecutive days to induce kidney damage. The pharmacokinetic variables were calculated in both cases. Kidney damage caused several changes in the determined variables. The Cmax and Cmin of cefotaxime observed at 0.50 and 5 h in normal goats were 24.91+/-1.51 and 1.22+/-0.07 microgram/ml, respectively, while the same in kidney damaged goats at 1 and 72 h were 75.00+/-0.45 and 3.10+/-0.09 microgram/ml, respectively. Renal damage condition significantly increased t1/2,ka (0.48+/-0.01 h), t1/2,ke (20.03+/-0.16 h), AUC (2440.10+/-24.26 microgram. h/ml) and significantly decreased Vdarea (0.59+/-0.007L/kg), Vss (0.58+/-0.007 L/kg) and ClB (0.02+/-0.008 L/kg/h) values of cefotaxime compared to normal goats.
Animals ; Anti-Bacterial Agents/blood/*pharmacokinetics ; Area Under Curve ; Cefotaxime/blood/*pharmacokinetics ; Female ; Goat Diseases/chemically induced/*metabolism ; Goats ; Half-Life ; Injections, Intramuscular ; Kidney Failure/chemically induced/*metabolism ; Uranyl Nitrate