PMID: 9751451Sep 29, 1998

Time-dependent effects of Klebsiella pneumoniae endotoxin on hepatic drug-metabolizing enzyme activity in rats

The Journal of Pharmacy and Pharmacology
M NadaiT Hasegawa

Abstract

The time-dependent effects of Klebsiella pneumoniae endotoxin on hepatic cytochrome P450-dependent drug-metabolizing capacity (cytochrome P450 and b5 content, activity of aminopyrine N-demethylase, p-nitroanisole O-demethylase, aniline hydroxylase and benzphetamine N-demethylase) and on the pharmacokinetics of antipyrine have been determined in rats. Measurement of enzyme activity and antipyrine (after intravenous injection of 20 mg kg(-1)) were performed 2, 24 and 96 h after a single intraperitoneal injection of endotoxin (1 mg kg(-1)) and after repeated doses (once daily for 4 days). The contribution of tumour necrosis factor alpha (TNFalpha) to the endotoxin-induced changes was also examined in rats pretreated with granulocyte colony-stimulating factor (G-CSF). The systemic clearance of antipyrine and the activity of hepatic cytochrome P450-dependent drug-metabolizing enzymes were dramatically reduced 24 h after a single injection of endotoxin, but had returned to control levels by 96h. The magnitudes of these decreases in these measurements after repeated doses of endotoxin were similar to those seen 24h after the single dose. The systemic clearance of antipyrine correlated significantly with cytochrome P450 content and ami...Continue Reading

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Citations

Sep 23, 2008·Archives of Pharmacal Research·Kyung Hee Yang, Myung G Lee
Dec 6, 2001·European Journal of Pharmacology·M NadaiT Hasegawa
Jun 18, 2002·European Journal of Pharmacology·Ying Lan ZhaoTakaaki Hasegawa
Nov 16, 2001·Antimicrobial Agents and Chemotherapy·H AndoT Hasegawa
Sep 14, 2010·Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy·Takayuki NodaTakaaki Hasegawa
Apr 20, 2007·Toxicology Letters·Jun UeyamaTakaaki Hasegawa
Feb 6, 2007·International Journal of Pharmaceutics·Young H ChoiMyung G Lee
Mar 2, 2005·Toxicology and Applied Pharmacology·C Wiegand, S Pflugmacher
Aug 2, 2008·Biological & Pharmaceutical Bulletin·Jun UeyamaTakaaki Hasegawa

Related Concepts

Analgesics, Anti-Inflammatory
Pyramidone
Cytochrome P-450 Oxygenase
Endotoxins
Klebsiella rhinoscleromatis
Liver
Tumor Necrosis Factor-alpha
Granulocyte Colony-Stimulating Factor
Rats, Wistar
Area Under Curve

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