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

Urease was immobilized in a simple and effective way by physical aggregation using a precipitant-ammonium sulfate, followed by chemical cross-linking using a bifunctional reagent-glutaraldehyde to form insoluble Cross-linked urease aggregates (CLUAs). The optimum pH, optimum temperature and Km of CLUAs were 8.0, 70 degrees C and 0.021 mol/L respectively. Compared with that of free urease, the thermal stability, storage stability and resistance of cross-linked urease aggregates to the exogenous proteolysis were enhanced. The efficacy of CLUAs for the treatment of rats with chronic renal failure was also studies. The rats with chronic renal failure caused by adenine were divided into 3 groups randomly:the control group (fed with 10 mL water /kg per day), Coated Aldehyde Oxystarch (CAO) group (fed with 20 g CAO /kg and 10 mL water /kg per day) and CLUAs + CAO group (fed with 20 g CAO /kg and 10 mL CLUAs /kg per day) in which CAO was used to absorb the ammonia produced from urea. The contents of BUN and Scr in serum before and after 2 weeks treatment were determined. In three groups, the level of Scr decreased slightly (P = 0.922, 0.972 and 0.225 > 0.05 respectively) after treatment. The level of BUN was not changed (P = 0.211 > 0.05) in the control group, but decreased greatly BUN in both CAO group and CLUAs + CAO group (P = 0.004 < 0.05 and P < 0.001 respectively). Furthermore, the decrease of the BUN level after treatment in the CLUAs + CAO group was more remarkable than that in the CAO group (P = 0.016 < 0.05), which showed that the CLUAs + CAD system was more efficient than the CAO system for the removal of urea in serum.
Adenine ; toxicity ; Animals ; Enzyme Stability ; Female ; Glutaral ; chemistry ; Hydrogen-Ion Concentration ; Kidney Failure, Chronic ; chemically induced ; drug therapy ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Temperature ; Urea ; blood ; Urease ; blood ; chemistry ; metabolism ; therapeutic use

5-Lipoxygenase inhibitor and human recombinant erythropoietin might accelerate renal recovery in cisplatin-induced acute renal failure rats. Male Sprague-Dawley rats were randomized into four groups: 1) normal controls; 2) Cisplatin group-cisplatin induced acute renal failure (ARF) plus vehicle treatment; 3) Cisplatin+nordihydroguaiaretic acid (NDGA) group-cisplatin induced ARF plus 5-lipoxygenase inhibitor treatment; 4) Cisplatin+erythropoietin (EPO) group-cisplatin induced ARF plus erythropoietin treatment. On day 10 (after 7 daily injections of NDGA or EPO), urea nitrogen and serum Cr concentrations were significantly lower in the Cisplatin+NDGA and Cisplatin+EPO groups than in the Cisplatin group, and 24 hr urine Cr clearances were significantly higher in the Cisplatin+EPO group than in the Cisplatin group. Semiquantitative assessments of histological lesions did not produce any significant differences between the three treatment groups. Numbers of PCNA(+) cells were significantly higher in Cisplatin, Cisplatin+NDGA, and Cisplatin+EPO groups than in normal controls. Those PCNA(+) cells were significantly increased in Cisplatin+NDGA group. These results suggest that EPO and also NDGA accelerate renal function recovery by stimulating tubular epithelial cell regeneration.
Animals ; Arachidonate 5-Lipoxygenase/administration & dosage ; Blood Urea Nitrogen ; Cisplatin/*toxicity ; Creatinine/urine ; Epithelial Cells/drug effects ; Erythropoietin/administration & dosage/*therapeutic use ; Kidney/metabolism ; Kidney Failure, Acute/*chemically induced/*drug therapy ; Kidney Tubules/drug effects ; Male ; Nordihydroguaiaretic Acid/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; Regeneration

The protective effect of erythropoietin (EPO) on tissues following ischemia and reperfusion injuries remains poorly understood. We aimed to investigate the effect of EPO in preventing endotoxin-induced organ damage. Rat model of multiple organ failure (MOF) was established by tail vein injection of 10 mg/kg lipopolysaccharide (LPS). Recombinant human EPO treatment (5000 U/kg) was administered by tail vein injection at 30 min after LPS challenge. Twenty-four h after EPO treatment, changes in serum enzyme levels, including aspartate aminotransferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN) and creatinine (Cr), were evaluated by biochemical analysis. Serum levels of tumor necrosis factor-α (TNF-α) were determined by using immunoradiometric assay. Histological examination of tissue sections was carried out by hematoxylin and eosin staining, while ultrastructure evaluation of organ tissues was assessed by transmission electron microscopy. Protein expression levels were detected by using Western blotting. EPO treatment showed a modest effect in preventing LPS-induced elevation of AST, ALT, BUN, Cr, and TNF-α levels, and in protecting against LPS-induced tissue degeneration and injured ultrastructure in the lung, liver, and kidney. Moreover, LPS promoted phosphorylation of alanine aminotransferase (AKT) and increased nuclear factor-κB (NF-κB) activation in the lung, liver, and kidney (P<0.05 vs. control). However, EPO treatment significantly decreased the LPS-induced pAKT up-regulation in these tissues (P<0.05 vs. LPS treatment alone). The present study demonstrates that EPO may play a protective role against LPS-induced MOF by reducing the inflammatory response and tissue degeneration, possibly via the phosphatidylinositol 3-kinase/AKT and NF-κB signaling pathways.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Urea Nitrogen ; Blotting, Western ; Creatinine ; blood ; Endotoxins ; Erythropoietin ; administration & dosage ; genetics ; pharmacology ; Injections, Intravenous ; Kidney ; drug effects ; metabolism ; ultrastructure ; Lipopolysaccharides ; Liver ; drug effects ; metabolism ; ultrastructure ; Lung ; drug effects ; metabolism ; ultrastructure ; Male ; Microscopy, Electron, Transmission ; Multiple Organ Failure ; blood ; chemically induced ; prevention & control ; NF-kappa B ; metabolism ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Wistar ; Recombinant Proteins ; administration & dosage ; pharmacology ; Tumor Necrosis Factor-alpha ; blood