Comparison of hepatic and extrahepatic drug-metabolizing enzyme activities in rats given single or multiple challenge infections with Fasciola hepatica

Biro-Sauveur, B.; Eeckhoutte, C.; Baéza, Élisabeth; Boulard, C.; Galtier, P.

doi:10.1016/0020-7519(95)00035-z

Cited by 19 publications

(4 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to HeOu mice, several renal P450 mRNAs in HeJ mice were significantly increased after C. rodentium infection. This may be a compensatory effect for down-regulation of hepatic P450s, as has been suggested for Fasciola hepatica-infected rats with decreased hepatic P450 activities, which also have increased renal P450 activities (Biro-Sauveur et al, 1995). It is unclear why this increase in renal P450s is only seen in HeJ mice, and not in HeOu mice.…”

Section: Discussionmentioning

confidence: 67%

HEPATIC AND RENAL CYTOCHROME P450 GENE REGULATION DURINGCITROBACTER RODENTIUMINFECTION IN WILD-TYPE AND TOLL-LIKE RECEPTOR 4 MUTANT MICE

Richardson¹,

Sherman²,

Antonovic³

et al. 2005

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:Citrobacter rodentium is the rodent equivalent of human enteropathogenic Escherichia coli infection. This study investigated regulation of hepatic and renal cytochrome P450 (P450) mRNAs, hepatic P450 proteins, cytokines, and acute phase proteins during C. rodentium infection. Female C3H/HeOuJ (HeOu) and C3H/HeJ (HeJ) mice [which lack functional toll-like receptor 4 (TLR4)] were infected with C. rodentium by oral gavage and sacrificed 6 days later. Hepatic CYP4A10 and 4A14 mRNAs were decreased in HeOu mice (<4% of control). CYP3A11, 2C29, 4F14, and 4F15 mRNAs were reduced to 16 to 55% of control levels, whereas CYP2A5, 4F16, and 4F18 mRNAs were induced (180, 190, and 600% of control, respectively). The pattern of P450 regulation in HeJ mice was similar to that in HeOu mice for most P450s, with the exception of the TLR4 dependence of CYP4F15. Hepatic CYP2C, 3A, and 4A proteins in both groups were decreased, whereas CYP2E protein was not. Renal CYP4A10 and 4A14 mRNAs were significantly down-regulated in HeOu mice, whereas other P450s were unaffected. Most renal P450 mRNAs in infected HeJ mice were increased, notably CYP4A10, 4A14, 4F18, 2A5, and 3A13. Hepatic levels of interleukin (IL)-1␤, IL-6, and tumor necrosis factor ␣ (TNF␣) mRNAs were significantly increased in infected HeOu mice, whereas only TNF␣ mRNA was significantly increased in HeJ mice. Hepatic ␣ 1 -acid glycoprotein was induced in both groups, whereas ␣-fibrinogen and angiotensinogen were unchanged. These data indicate that hepatic inflammation induced by C. rodentium infection is mainly TLR4-independent and suggest that hepatic P450 down-regulation in this model may be cytokine-mediated.

show abstract

Section: Discussionmentioning

confidence: 67%

HEPATIC AND RENAL CYTOCHROME P450 GENE REGULATION DURINGCITROBACTER RODENTIUMINFECTION IN WILD-TYPE AND TOLL-LIKE RECEPTOR 4 MUTANT MICE

Richardson¹,

Sherman²,

Antonovic³

et al. 2005

Drug Metab Dispos

View full text Add to dashboard Cite

show abstract

“…Indeed, infection with H. contortus induced antipyrine clearance in lambs (Kawalek and Fetterer 1990), consistent with an increase in cytochrome P450 activity. Similarly, Fasciola hepatica infection influenced biotransformation enzyme activities in sheep (Galtier et al 1991;Benchaoui and McKellar 1993;Biro-Sauveur et al 1995). The influence of parasitism on biotransformation enzymes may be a determinant in parental drug level in the treated host.…”

Section: Discussionmentioning

confidence: 95%

The influence of parasitism on the pharmacokinetics of moxidectin in lambs

Lespine

Sutra

Dupuy³

et al. 2004

Parasitology Research

View full text Add to dashboard Cite

Most pharmacokinetic studies on anthelmintic drugs have been performed on non-parasitized animals. However, it seems likely that the parasite burden could influence the deposition of such drugs. The pharmacokinetics of moxidectin administered orally and by subcutaneous injection was compared in lambs exposed to nematode infection and in parasite naive lambs. Plasma samples were analyzed for moxidectin over 40 days post-treatment. The main pharmacokinetic parameters calculated demonstrated a significant change in drug deposition in infected lambs when compared to controls. The area under the plasma concentration-time curve was decreased 54% and 46% by infection in the subcutaneous and oral groups, respectively. There was also a major decrease in the mean residence time in parasitized lambs. In parallel, the clearance of the drug was increased by infection. Thus, parasite infection dramatically influences the disposition of moxidectin in lambs. These results may contribute to determining a therapeutic strategy adapted to heavily infested animals.

show abstract

“…Regarding the eect of experimental parasitism on the activity of microsomal drug-metabolising enzymes, a signi®cant decrease has been observed in the liver of infected animals (Tekwani et al 1988;Calleja et al 1997), but the increase of some monooxygenase activities has been described as a compensatory mechanism in infected rats (Biro-Sauveur et al 1995). Our study shows that microsomal sulfoxidase activity in the small intestine of infected gerbils decreased, whereas it increased in the liver.…”

Section: Discussionmentioning

confidence: 47%

Pharmacokinetics of netobimin and microsomal metabolism of albendazole in infected gerbils with Echinococcus granulosus

García-Llamazares

Merino²,

Larrode-Pellicer³

et al. 2001

Parasitology Research

View full text Add to dashboard Cite

A comparison of the pharmacokinetic profiles of netobimin (NTB), albendazole sulfoxide (ABZSO) and albendazole sulfone (ABZSO2) was performed in gerbils (Meriones unguiculatus) with intra-abdominal hydatidosis and in healthy gerbils. The infection was developed after peritoneal inoculation of protoscolices of Echinooccus granulosus from sheep. Plasma concentrations of NTB, ABZSO and ABZSO2 were measured by HPLC after oral administration of 50 mg NTB kg(-1). The results showed an incomplete biotransformation of NTB over the experimental time; and this increased in infected animals. ABZSO and ABZSO2 pharmacokinetic profiles were unaffected and were similar in both non-infected and infected animals. Both hepatic and intestinal microsomal sulfoxidase activities were measured. Since infected gerbils induced hepatic activity and decreased intestinal activity, the total activity was not different in infected and non-infected animals. In summary, intra-abdominal hydatid disease affected the pharmacokinetic profile of NTB, but ABZSO and ABZSO2 plasma concentrations were not different in infected and non-infected gerbils.

show abstract

Comparison of hepatic and extrahepatic drug-metabolizing enzyme activities in rats given single or multiple challenge infections with Fasciola hepatica

Cited by 19 publications

References 28 publications

HEPATIC AND RENAL CYTOCHROME P450 GENE REGULATION DURINGCITROBACTER RODENTIUMINFECTION IN WILD-TYPE AND TOLL-LIKE RECEPTOR 4 MUTANT MICE

HEPATIC AND RENAL CYTOCHROME P450 GENE REGULATION DURINGCITROBACTER RODENTIUMINFECTION IN WILD-TYPE AND TOLL-LIKE RECEPTOR 4 MUTANT MICE

The influence of parasitism on the pharmacokinetics of moxidectin in lambs

Pharmacokinetics of netobimin and microsomal metabolism of albendazole in infected gerbils with Echinococcus granulosus

Contact Info

Product

Resources

About