Effect of endotoxin to differentially affect cytochrome P-450 monooxygenase activities of untreated rats and animals induced with phenobarbital or 3-methylcholanthrene

Coto, Jorge A.; Williams, Joseph F.

doi:10.1016/0192-0561(89)90147-1

Cited by 7 publications

(2 citation statements)

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“…DTP vaccine administration reduced cytochrome P-450 levels at 24 h 30 to 40% in both strains of mice, whereas LPS (E. coli or B. pernussis) caused a significant reduction in P-450 levels only in R mice ( Table 1). The observed effects of LPS administration are consistent with other reports of alterations in hepatic drug metabolism in rodents (8,12,15,28,35,36). However, this is the first report describing alterations in hexobarbital-induced sleep time, cytochrome P-450 levels, and other microsomal enzyme activities by LPS and vaccine administration in R and NR mice.…”

Section: Discussionsupporting

confidence: 91%

Role of endotoxin in alterations of hepatic drug metabolism by diphtheria and tetanus toxoids and pertussis vaccine adsorbed

et al. 1992

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Administration of diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTP vaccine) or endotoxin (LPS) resulted in marked alterations in hepatic drug-metabolizing enzymes in endotoxin-responsive (R) and non-endotoxin-responsive (NR) mice. A single human dose (0.5 ml) of DTP vaccine increased hexobarbitalinduced sleep times to 1.6to 1.8-fold above those of controls in both strains of mice. This effect persisted for 7 days. In contrast, BordeteUa pertussis LPS-treated mice showed an increase at 1 day (3.0-fold for R mice and 1.5-fold for NR mice), which returned to control levels by day 7. Furthermore, cytochrome P-450 levels were decreased 30 to 40% 24 h after DTP vaccine administration in both R and NR mice, while after LPS administration they were decreased 30%o in R mice and less than 10% in NR mice. Both spleen and liver weights of R and NR mice were increased 7 to 14 days following DTP vaccine administration. However, LPS treatment had no apparent effect on liver weights, and spleen weights of R mice were elevated from days 3 to 7. Histopathologic tissue examination showed random, multifocal inflammation with hepatocyte necrosis after DTP vaccine administration to both R and NR mice and an absence of lesions in LPS-treated mice. Premixing LPS with polymyxin eliminated the increased sleep times, but premixing DTP vaccine with polymyxin did not affect the increased sleep times. Levels of tumor necrosis factor and interleukin-6 in plasma of R mice were 3790 on August 1, 2020 by guest http://iai.asm.org/ Downloaded from

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Section: Discussionsupporting

confidence: 91%

Role of endotoxin in alterations of hepatic drug metabolism by diphtheria and tetanus toxoids and pertussis vaccine adsorbed

et al. 1992

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“…The alteration of drug metabolism under diseased conditions is of clinical importance. Many reports have shown that several hepatic CYP isozymes were down-regulated during systemic infection [5,19] and inflammation caused by peripheral injection of lipopolysaccharide (LPS), bacterial endotoxin, [4,11,12] and inflammatory cytokines such as interleukin (IL)-1 [6, 13, 17], IL-6 [2, 13] and tumor necrosis factor (TNF)-α [1]. However, the reports indicating that central inflammation has any effect on the activities and levels of drug metabolizing enzymes are limited.…”

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confidence: 99%

Decrease in Hepatic CYP2C11 mRNA and Increase in Heme Oxygenase Activity after Intracerebroventricular Injection of Bacterial Endotoxin.

Shimamoto

Tasaki

Kitamura

et al. 1999

The Journal of Veterinary Medical Science

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ABSTRACT. We previously reported (Arch. Toxcol. 1998, 72, 492-498) that the differential decrease in the levels of hepatic cytochrome P450 (CYP) isozymes in rats was observed 24 hr after intracerebroventricular (icv) injection of bacterial lipopolysaccharide (LPS) at the dose ineffective (0.1 µg) when injected intraperitoneally (ip). Among CYP isozymes we examined, the male specific CYP isozyme, CYP2C11 was most severely affected by icv injection of LPS. In this study, we examined the gene expression of CYP2C11, the total P450 contents, the CYP2C11-dependent activity of imipramine N-demethylase (IMND) and protein of CYP2C11 10 hr after icv or ip injections of LPS. Intracerebroventricular injection of LPS significantly decreased the level of CYP2C11 mRNA (to 63% of saline icv control), the total P450 contents (to 70% of saline icv control), the IMND activity (to 74% of saline icv control), but not protein of CYP2C11 in rat liver. In contrast, ip injection of LPS at the same dose as icv did not significantly affect these parameters. Since CYP is a heme protein, we also measured the activity of heme oxygenase (HO) using the same rat liver microsomes. The HO activity was increased to 166% by icv injection of LPS and 135% by ip injection of LPS compared to corresponding saline control. It is suggested that icv injection of LPS down-regulates the expression of CYP2C11 at transcriptional level and that both the decrease in CYP2C11 mRNA and the increase in heme degradation may be involved in the decreased level of protein and activity of CYP2C11 by icv injection of LPS in rat liver.-KEY WORDS: CYP2C11, cytochrome P450, intracerebroventricular, lipopolysaccharide, messenger RNA.J. Vet. Med. Sci. 61(6): 609-613, 1999 injection of LPS. In this study, to clarify the mechanism of the down-regulation of this isozyme by icv injection of LPS, we first examined the expression of CYP2C11 mRNA and the level of protein of CYP2C11 and its drug metabolizing activity in rat liver 10 hr after icv injection of LPS. Furthermore, to estimate the effect of icv injection of LPS on heme degradation, we also measured the activity of heme oxygenase using the same rat liver microsomes. MATERIALS AND METHODSChemicals: LPS (Escherichia coli 0111: B4), imipramine hydrochloride and desipramine were purchased from Sigma (St. Louis, Mo.). 2-Hydroxyimipramine was kindly donated by Geigy (Basel, Switzerland). Hemin and bilirubin were purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan). All other chemicals and solvents were of analytical grade.Treatment of animals and preparation of liver microsomes: Male Wistar rats (Nihon SLC, Hamamatsu, Japan) weighing 210-230 g were housed in plastic cages at 24 ± 1˚C with a 12-hr light-dark cycle (lights on at 7:00-19:00) and given laboratory chow and water ad lib. All rats were anesthetized with sodium pentobarbital at a dose of 40 mg/kg by intraperitoneal (ip) injection and implanted with a sterilized polyethylene cannula (0.6 mm o.d.) in the right lateral cerebral ventricle (at the bregma, 3.6 ...

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Effect of interleukin 6 on phenobarbital induction of cytochrome P-450IIB in cultured rat hepatocytes

Williams

Bement

Sinclair

et al. 1991

Biochemical and Biophysical Research Communications

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Effect of endotoxin to differentially affect cytochrome P-450 monooxygenase activities of untreated rats and animals induced with phenobarbital or 3-methylcholanthrene

Cited by 7 publications

References 11 publications

Role of endotoxin in alterations of hepatic drug metabolism by diphtheria and tetanus toxoids and pertussis vaccine adsorbed

Role of endotoxin in alterations of hepatic drug metabolism by diphtheria and tetanus toxoids and pertussis vaccine adsorbed

Decrease in Hepatic CYP2C11 mRNA and Increase in Heme Oxygenase Activity after Intracerebroventricular Injection of Bacterial Endotoxin.

Effect of interleukin 6 on phenobarbital induction of cytochrome P-450IIB in cultured rat hepatocytes

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