Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male adult Sprague-Dawley rats were treated for 14 days with either rapamycin (RAP, 1.5 mg/kg/d i.p.) in carboxymethylcellulose (RAP/CMC) or polyethyleneglycol (RAP/PEG), cyclosporine (CsA, 15 mg/kg/d by gavage) or with the appropriate drug vehicles. Biochemical indices of renal function and integrity were determined throughout the experimental period, at the end of which the rats were killed and kidneys examined histologically. All animals gained weight at a similar rate to untreated animals except those treated with RAP; RAP/PEG animals were lighter on day 14 compared with day 0 values, whilst RAP/CMC animals were lighter only in comparison with CMC-only controls on day 14. Significant increases in urinary flow rate (UFR) were found in each drug treatment group. RAP/CMC, RAP/PEG and CsA caused mild renal functional impairment, but only with CsA was there a significant reduction in 51Cr-EDTA clearance. Significant enzymuria, resulting from drug but not vehicle administration, was observed only in the CsA-treatment group. Increased plasma and urinary glucose levels, elevated in all drug-treatment groups, were related to increased UFR. Kidneys of RAP-treated rats appeared normal, whereas mild, focal, acute tubular necrosis was evident in all CsA-tested animals. Pancreases of all drug-treated animals were histologically normal.
 ...
PMID:The effect of rapamycin on renal function in the rat: a comparative study with cyclosporine. 168 33

Sprague-Dawley rats were treated for 14 days with rapamycin (RAP; 1.5 mg/kg/day i.p.), cyclosporine (15 mg/kg/day by gavage), both drugs in combination, or appropriate drug vehicles. Hematological parameters and biochemical indices of renal and hepatic function were determined throughout the experimental period, at the end of which the rats were killed and tissues examined histologically. There was a significant reduction in weight gain in RAP- but not CsA-treated animals, while rats given both drugs showed a reduction in body weight over the 14-day experimental period. There were no significant alterations in absolute or differential white blood cell counts or in T or B cell numbers, except in the drug combination group, in which an absolute lymphopenia was detected on day 14. Small but significant increases in urinary flow rate (UFR) were found with either drug alone, and there was a marked (4-fold) increase in UFR in response to drug combination. Both RAP and CsA caused a small elevation in serum creatinine concentrations, but only with CsA was there a significant elevation in urinary enzyme activity and reduction in 51Cr. EDTA clearance. The drug combination exacerbated renal impairment, the extent of which was greater than the additive effect of either drug alone. Hyperbilirubinemia of similar magnitude was observed in rats receiving either CsA alone or in combination with RAP. In contrast to its effect on renal function, however, the CsA+RAP combination was without additional effect on liver function compared with the minor changes seen with either drug alone. Plasma and urinary glucose levels were elevated in all drug treatment groups and especially in animals given both drugs. RAP administration did not significantly affect whole-blood CsA concentrations, although the possibility of a pharmacokinetic interaction cannot be totally excluded. Histological studies revealed striking thymic medullary atrophy in all drug-treated animals. In addition, all rats given RAP showed focal myocardial necrosis of overall mild-moderate severity. Kidneys of RAP-treated rats appeared normal, whereas mild, focal, acute tubular necrosis was evident in all CsA-treated animals. Pancreases of all drug-treated animals were normal.
 ...
PMID:Toxicity of rapamycin--a comparative and combination study with cyclosporine at immunotherapeutic dosage in the rat. 187 90