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1‐(8‐methoxy‐4,8‐dimethylnonyl)‐4‐(1‐methyl‐ethyl)benzene (MV‐678): A reversible inducer of rat hepatic microsomal drug metabolism

 

作者: RobertP. Clement,   GaryM. Zwicker,   TheodoreY. Chin,   RalphI. Freudenthal,  

 

期刊: Journal of Toxicology and Environmental Health  (Taylor Available online 1986)
卷期: Volume 19, issue 1  

页码: 111-125

 

ISSN:0098-4108

 

年代: 1986

 

DOI:10.1080/15287398609530912

 

出版商: Taylor & Francis Group

 

数据来源: Taylor

 

摘要:

MV‐678 [1‐(8‐methoxy‐4,8‐dimethynonyl)‐4‐(1‐methylethyl)benzene], a recently developed insect growth regulator, increased the hepatic cytochrome P‐450‐dependent monooxygenase enzymes that metabolize endogenous and exogenous chemicals. In an initial set of experiments, male and female rats received 0, 50, or 800 mg/kg·d of MV‐678 by gavage for 3 d, and in a second set of experiments, male rats received 0, 50, or 800 mg/kg·d of MV‐678 by gavage for 30 d. A significant incrase in both absolute and relative liver weight, microsomal protein content, cytochrome P‐450 content, NADPH‐cytochrome P‐450 reductase activity, and ehtylmorphine N‐demethylase activity was observed in male and female rats at the high dose level at 3 d. Similar increases were observed in the 800‐mg/kg·d males at 30 d. Hepatocellular hypertrophy and proliferation of endoplasmic reticulum observed at both 3 and 30 d correspond to and was consistent with microsomal enzyme induction. Reversibility of both induction and changes in morphology was determined by measuring the same parameters in animals treated for 30 d after a 15‐ or 30‐d recovery period. At 15 d recovery, all biochemical parameters at the high dose level, except relative liver weight and microsomal ethylmorphine N‐demethylase activity, had returned to control levels. No significant differences between the control and high dose group animals were noted at 30 d recovery. The hepatocellular changes observed in the high‐dose group at 30 d were less apparent at 15 d recovery, and absent at 30 d recovery.

 

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