Abstract:
:We have investigated the influence of phenobarbitone ([PB]; 40 mg/kg/day), an inducer of hepatic drug metabolism, on high-dose cyclosporine ([CsA] 40 mg/kg/day) nephrotoxicity in normal Lewis (Lew) and renal allografted (DA X Lew F1----Lew) rats of both sexes. In untreated normal animals, CsA nephrotoxicity, assessed biochemically and histologically, in terms of acute and chronic renal structural damage, was consistently greater in male than in female rats. The capacity of PB to induce CsA metabolism was accompanied in normal rats by reductions in nephro- and hepatotoxicity and by prolonged survival of both female and male rats. Similar reductions in CsA-induced renal functional impairment and acute tubular cell injury were achieved in transplanted female (but not male) animals by concomitant PB administration. Continuous PB treatment in transplanted rats was, however, associated with the appearance of hepatic necrosis. While this effect of PB, and its failure to reduce CsA-induced chronic renal damage mitigate against its prospective value in reversing CsA toxicity, PB may nevertheless prove valuable in assessing further the role of drug metabolism in the pathogenesis of CsA nephrotoxicity.
journal_name
Transplantationjournal_title
Transplantationauthors
Duncan JI,Heys SD,Thomson AW,Simpson JG,Whiting PHdoi
10.1097/00007890-198804000-00005subject
Has Abstractpub_date
1988-04-01 00:00:00pages
693-7issue
4eissn
0041-1337issn
1534-6080journal_volume
45pub_type
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