当前位置： SCI文献检索 > TRANSPLANTATION期刊下所有文献 > Toxicity of rapamycin--a comparative and combination study with cyclosporine at immunotherapeutic dosage in the rat.

Toxicity of rapamycin--a comparative and combination study with cyclosporine at immunotherapeutic dosage in the rat.

Abstract：

: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.

journal_name

Transplantation

journal_title

Transplantation

authors

Whiting PH,Woo J,Adam BJ,Hasan NU,Davidson RJ,Thomson AW

doi

10.1097/00007890-199108000-00004

subject

Has Abstract

pub_date

1991-08-01 00:00:00

pages

203-8

issue

eissn

0041-1337

issn

1534-6080

journal_volume

pub_type

杂志文章

在线工具

Toxicity of rapamycin--a comparative and combination study with cyclosporine at immunotherapeutic dosage in the rat.