Modification of pharmacokinetics of cefotaxime in uranyl nitrate-induced renal damage in black bengal goats

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.

Evaluation of phytotoxicity and genotoxicity of uranyl nitrate in Allium assay system.

Uranyl nitrate inhibited root growth of Allium cepa at > or = 25 microM concentration. Fluorimetric analysis of metal uptake indicated the entry and accumulation of uranium into the root cell. Uranyl nitrate was neither clastogenic nor aneugenic as it failed to induce micronuclei significantly, but between 25 and 100 microM concentration, it increased significantly the frequency of sister chromatid exchange over that of control, implying its genotoxicity that possibly interfered with DNA replication and/or repair process.

Uranyl nitrate induced corpuscular derangement: an early indication of induced acute renal failure.

Erythrocyte structure was studied in rat after uranyl nitrate (UN:5 mg/kg) intoxication. The study of pathogenic progression of UN induced renal failure (ARF) was confined to the early initiation phase (2 hr), late initiation phase (8 hr) and the maintenance phase (24 hr). Erythrocyte structure has been found to be greatly influenced. The UN induced hemolytic syndrome/hypoxia was accompanied by a marked anisocytosis and poikilocytosis during different phases of ARF, which is characteristic of UN poisoning. Subsequent alterations in erythrocyte structure followed by UN administration or during the pathogenic progression of ARF has clinical and diagnostic importance as the alterations were much distinct prior to the clinical manifestation of ARF even at light microscopic level.

Uranyl Nitrate Induced Polyuric Acute Tubular Necrosis in Rats

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.

Acute toxicity of uranyl nitrate and behaviour of serum lipolytic activity.

The alterations in the serum lipolytic activity of mice were studied under Uranyl nitrate (UN) intoxication. The lipemia produced as a result of UN intoxication was probed studying the alterations in the serum triacyl-glycerol-hydrolase (EC 3.1.1.3) activity. After an intraperitoneal injection of UN (10 mg/kg and 25 mg/kg), triacyl-glycerol-hydrolase (TAGH) activity was considerably enhanced. In the initiation phase the elevation in the activity was observed to be higher than the elevation in the maintenance phase of acute UN toxicity. The possible reasons for the elevation in the TAGH activity and its role under such intoxication is discussed.