The purpose of this study was to determine what histological changes, if any, accompany @entity382 and microsomal enzyme induction in @entity35 administered high doses of therapeutic agents in preclinical toxicology studies. This was accomplished by evaluating a database derived from a series of 11 induction studies in @entity35 with 10 novel compounds comprising five therapeutic classes. Results from serum enzyme chemistry analyses, gross organ weight changes, and histological analyses of the liver sections were evaluated and compared with the magnitude and extent of hepatic @entity1447 induction. All compounds were administrated via oral intubation once a day for the duration of the study using multiple doses, each proportionally based on body weight. During the course of these studies, serum clinical chemistry data and clinical observations were recorded. After necropsy, histopathology observations were made, and hepatic microsomes were assayed for @entity1447 content and associated drug-metabolizing enzymes. In some cases, @entity3789 -insensitive beta-oxidation of @entity11668 was also assayed. Liver weight increases of 20% or greater were associated with histological evidence of @entity1184 , but neither the severity of @entity1184 nor the magnitude of liver weight increase correlated with the magnitude of drug-metabolizing enzyme elevations. @entity1184 alone was not associated with serum enzyme increases. While there was a correlation between the incidence of increased liver weights and microsomal enzyme induction, the magnitudes of these increases were not related. Decreased serum @entity1674 were often associated with elevated beta-oxidation attributed to hepatic peroxisome proliferation. It was concluded that, while slight ALT elevations occasionally were observed, hepatic microsomal enzyme induction was generally not accompanied by substantial morphological changes or elevated serum enzyme levels considered indicative of @entity99 .

The relationship among microsomal enzyme induction, liver weight and histological change in XXXX toxicology studies.

@entity1447 :: ('25251(Tax:10116)', 'Gene') :: ['cytochrome P450'] @entity1184 :: ('MESH:D006984', 'Disease') :: ['hypertrophy', 'Hypertrophy'] @entity1674 :: ('MESH:D014280', 'Chemical') :: ['triglycerides'] @entity3789 :: ('CHEBI:17514', 'Chemical') :: ['cyanide'] @entity382 :: ('MESH:D006529', 'Disease') :: ['liver enlargement'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity99 :: ('MESH:D056486', 'Disease') :: ['liver injury'] @entity11668 :: ('MESH:D010171', 'Chemical') :: ['palmitoyl CoA']
@entity35 :: (10116,Species) :: ['rat']
