Effects of interleukin-6 on cytochrome P450-dependent mixed-function oxidases in the rat

Chen, Y.L.; Florentin, I.; Batt, Anne-Marie; Ferrari, Luc; Giroud, Jean‐Paul; Chauvelot‐Moachon, Laurence

doi:10.1016/0006-2952(92)90047-m

Cited by 102 publications

(40 citation statements)

References 52 publications

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“…Moreover, changes in hepatic UGT protein and/or activities during inflammation are also documented. Chen et al (1992) showed significantly decreased rat UGT activities toward 1-naphthol and p-nitrophenol (UGT1A6), and testosterone (UGT2B3) after administration of LPS (to 77-83% of control). Strasser et al (1998) found that glucuronidation of testosterone was decreased to 65% of control, whereas activity toward p-nitrophenol was unchanged in turpentine-treated rats.…”

Section: Resultsmentioning

confidence: 99%

“…In contrast to P450s, very little data exist on UGT regulation during LPS-induced inflammation. Significant decreases in hepatic UGT activities were reported after LPS administration in rats and isolated perfused mouse liver (Chen et al, 1992;Banhegyi et al, 1995), but no effect on UGTs was found in mouse hepatocytes (Banhegyi et al, 1995). Glucuronidation was unchanged after injection of individual cytokines in rats (Chen et al, 1992), yet it was inhibited in isolated pig hepatocytes after cytokine administration (Monshouwer et al, 1996).…”

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confidence: 99%

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EXPRESSION OF UDP-GLUCURONOSYLTRANSFERASE ISOFORM mRNAS DURING INFLAMMATION AND INFECTION IN MOUSE LIVER AND KIDNEY

Richardson¹,

Sherman²,

Kalman³

et al. 2005

Drug Metab Dispos

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ABSTRACT:Inflammation or infection down-regulates the activity and expression of cytochrome P450 (P450) enzymes involved in hepatic drug clearance, possibly altering drug effectiveness and leading to toxicity. The regulation of UDP-glucuronosyltransferases (UGTs) in inflammation and infection is less well characterized. To determine the response of hepatic and renal UGTs during inflammation and infection, mice were administered either saline or 1 mg/kg lipopolysaccharide (LPS) (16 h), or Citrobacter rodentium by oral gavage (6 days). Hepatic mRNA expression of UGT1A1, 1A9, and 2B5 was similarly down-regulated after LPS exposure and C. rodentium infection, whereas UGT1A2 and 1A6 mRNAs were unchanged. Effects of C. rodentium infection did not require a functional Toll-like receptor 4. Conversely, renal UGT isoforms were relatively unaffected, except for UGT2B5 induction after LPS treatment. Regulation of UGTs during the inflammatory response exhibits similarities to and differences from regulation of P450s, and may be cytokinemediated.UDP-glucuronosyltransferases (UGTs) reside in the endoplasmic reticulum and catalyze the biotransformation of a variety of substrates (Wells et al., 2004). Addition of glucuronic acid by UGTs generally increases the water solubility of compounds for subsequent excretion in bile or urine. UGTs have multiple constitutive and inducible isoforms with overlapping substrate specificities, and are expressed in both hepatic and extrahepatic tissues (Wells et al., 2004).Inflammation and infection can alter drug metabolism in humans and rodents, resulting in significantly increased or decreased drug efficacy and potential toxicity. Both cytochrome P450 (P450) expression and metabolic activities in liver and extrahepatic tissues can be down-regulated during inflammation Renton, 2004). However, little is known regarding UGT activities during the inflammatory response. Because hepatic P450 metabolism is significantly suppressed during inflammation, hepatic glucuronidation may be similarly affected and may contribute to alterations in drug efficacy.Injection of bacterial lipopolysaccharide (LPS) is a widely used model of inflammation and is well characterized regarding its effects on basal and inducible hepatic P450 expression. Many in vivo effects of LPS-induced inflammation are due to proinflammatory cytokines, and these cytokines mimic the effects of LPS when injected in vivo or incubated with hepatocytes Renton, 2004). In contrast to P450s, very little data exist on UGT regulation during LPS-induced inflammation. Significant decreases in hepatic UGT activities were reported after LPS administration in rats and isolated perfused mouse liver (Chen et al., 1992;Banhegyi et al., 1995), but no effect on UGTs was found in mouse hepatocytes (Banhegyi et al., 1995). Glucuronidation was unchanged after injection of individual cytokines in rats (Chen et al., 1992), yet it was inhibited in isolated pig hepatocytes after cytokine administration (Monshouwer et al., 1996). Even less information exists regar...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

EXPRESSION OF UDP-GLUCURONOSYLTRANSFERASE ISOFORM mRNAS DURING INFLAMMATION AND INFECTION IN MOUSE LIVER AND KIDNEY

Richardson¹,

Sherman²,

Kalman³

et al. 2005

Drug Metab Dispos

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“…The mechanism of this inhibitory effect of viral vaccine has not been investigated in the present study. However, it has been speculated that interferon induced during viral infection may have played a role (Buynitzky, 1976;Monshouwer et al, 1996), since proinflammatory cytokines, including interferons, are able to inhibit CYP450-mediated drug metabolism in mammals (Shedlofsky et al, 1987;Wright and Morgan, 1991;Chen et al, 1992;Cribb et al, 1994). Moreover, Sharma (1989) demonstrated interferon activity in tissues of turkey herpesvirus-exposed chickens and chickens embryos.…”

Section: Discussionmentioning

confidence: 99%

Marek's disease vaccination, with turkey herpesvirus, and enrofloxacin modulate the activities of hepatic microsomal enzymes in broiler chickens

Sakar

Prukner‐Radovčić

Crnić

et al. 2004

Acta Veterinaria Hungarica

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Chickens were vaccinated against Marek's disease intramuscularly at one day of age. Enrofloxacin was given ad libitum in the drinking water at concentrations of 50, 100 and 250 mg/L from 8 days to 13 days of age when the animals were killed and the activities of cytochrome P-450 enzymes in the liver were measured. Vaccinated non-treated chickens served as a positive control. A negative control group was neither vaccinated nor treated. Vaccination decreased the activity of aniline hydroxylase and ethylmorphine N-demethylase in the positive control group. Subsequent application of enrofloxacin in the lowest concentration (50 mg/L) decreased, while that given at the highest level (250 mg/L) significantly increased the activity of the same microsomal enzymes. Relative liver weights and concentrations of proteins in 9000 × g supernatant were not affected by vaccination or treatment.

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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.…”

Section: Methodsmentioning

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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Effects of interleukin-6 on cytochrome P450-dependent mixed-function oxidases in the rat

Cited by 102 publications

References 52 publications

EXPRESSION OF UDP-GLUCURONOSYLTRANSFERASE ISOFORM mRNAS DURING INFLAMMATION AND INFECTION IN MOUSE LIVER AND KIDNEY

EXPRESSION OF UDP-GLUCURONOSYLTRANSFERASE ISOFORM mRNAS DURING INFLAMMATION AND INFECTION IN MOUSE LIVER AND KIDNEY

Marek's disease vaccination, with turkey herpesvirus, and enrofloxacin modulate the activities of hepatic microsomal enzymes in broiler chickens

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

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