Open AccessProliferative Response and Renewal of Hepatic Function Following Cocaine Administration In Mice
Author(s) -
Padilla George M.,
Kloss Michelle W.,
Rauckman Elmer J.,
Rosen Gerald M.
Publication year - 1984
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.1984.tb00577.x
Subject(s) - microsome , transaminase , hepatotoxin , medicine , pi , endocrinology , necrosis , chemistry , thymidine , cytochrome p450 , monooxygenase , dna synthesis , biology , biochemistry , enzyme , toxicity , dna
Experiments were undertaken to investigate the hepatic, temporal and spatial sequence of events following a single injection of cocaine, a known hepatotoxin. Centrilobular necrosis was induced in male mice (DBA/2Ha) 24 hr post‐injection (PI). the time course of hepatic damage was monitored by assaying microsomal cytochrome P 450 content, the activity of microsomal FAD‐containing monooxygenase (FAD‐M) and by determining the levels of serum glutamic pyruvic transaminase (SGPT). Kinetics of the onset of DNA synthesis were determined by autoradiography of thin liver sections and the incorporation of 3 H‐methyl thymidine into perchloric‐acid‐precipitable material. There was no increase in the labelling index (LI) and thymidine (TdR) incorporation in the first 24 hr PI. the LI rose to 14.6% and TdR incorporation showed a 5‐fold increase over control values 48 hr PI. Both indices declined slightly at 72 hr PI and returned to control values by 96 hr PI. In contrast, the cytochrome P 450 content declined by 69%, the FAD‐M activity dropped by 40% and the SGPT levels showed an 18‐fold increase at 24 hr PI, coincident with cytological signs of necrosis. Although the patterns of recovery differed between these selected enzymes, normal values were attained by 96 hr PI. These results demonstrate that cell damage and hepatic dysfunction precede the onset of DNA synthesis and subsequent proliferation.