CAR expression and inducibility of CYP2B genes in liver of rats treated with PB-like inducers

Pustylnyak, Vladimir O.; Gulyaeva, L. F.; Lyakhovich, V. V.

doi:10.1016/j.tox.2005.08.002

Cited by 17 publications

(13 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on previous observations of CYP2B induction by TPD (Pustylnyak et al 2007a), we hypothesize that TPD, like PB in both rats and mice and TCPOBOP in mice, induces the expression of CYP2B in rats via activation of CAR. The aim of the current study was to investigate the species-specific induction of CYP2B by TPD in relation to activation of CAR.…”

Section: Introductionmentioning

confidence: 76%

“…One μg of total RNA was used for synthesis of single-stranded cDNA. Multiplex PCR was performed as previously described (Pustylnyak et al 2005b(Pustylnyak et al , 2007a. The "housekeeping" genes, GAPDH and β-actin, were chosen as an endogenous internal controls to which other PCR amplification products were normalized.…”

Section: Cdna Synthesis and Multiplex Pcrmentioning

confidence: 99%

“…1). For example, PB induces CYP2B in livers of rats and mice, whereas ТСРОВОР (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene) induces СYP2B in mice only (Poland et al 1980(Poland et al , 1981Pustylnyak et al 2007a). On the other hand, 2,4,6-tryphenyldioxane-1,3 (TPD) is a highly effective inducer of CYP2В in rats, but not in mice (Mishin et al 1990;Pustylnyak et al 2007a).…”

Section: Introductionmentioning

confidence: 99%

“…For example, PB induces CYP2B in livers of rats and mice, whereas ТСРОВОР (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene) induces СYP2B in mice only (Poland et al 1980(Poland et al , 1981Pustylnyak et al 2007a). On the other hand, 2,4,6-tryphenyldioxane-1,3 (TPD) is a highly effective inducer of CYP2В in rats, but not in mice (Mishin et al 1990;Pustylnyak et al 2007a). Recently, we have demonstrated that these species differences in CYP2B induction occur because of differences of transcriptional activation of CYP2B genes (Pustylnyak et al 2007a).…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, 2,4,6-tryphenyldioxane-1,3 (TPD) is a highly effective inducer of CYP2В in rats, but not in mice (Mishin et al 1990;Pustylnyak et al 2007a). Recently, we have demonstrated that these species differences in CYP2B induction occur because of differences of transcriptional activation of CYP2B genes (Pustylnyak et al 2007a).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Species-specific induction of CYP2B by 2,4,6-tryphenyldioxane-1,3 (TPD)

et al. 2009

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 76%

Section: Cdna Synthesis and Multiplex Pcrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Species-specific induction of CYP2B by 2,4,6-tryphenyldioxane-1,3 (TPD)

et al. 2009

View full text Add to dashboard Cite

Identification of hepatotoxicity and renal dysfunction of pyrene in adult male rats

Zhu

Zhao

Wang

et al. 2018

Environmental Toxicology

View full text Add to dashboard Cite

Polycyclic aromatic hydrocarbons (PAHs) are a group of persistent organic pollutants primarily formed from the incomplete combustion of carbonaceous materials, and have adverse effects on human health. In this study, we investigated whether pyrene, a PAH consisting of 4 fused benzene rings, has adverse effects on rat. Adult male Sprague‐Dawly rats were treated daily by oral gavage with vehicle (corn oil) or pyrene at doses of 375, 750, 1500, or 2200 mg/kg/day for 4 days. The results showed that pyrene caused hepatotoxicity in rats. When compared with the control group, relative liver weights, plasma alanine aminotransferase, and direct bilirubin levels significantly increased after pyrene exposure. Hepatocyte swelling and degeneration and decreased hepatic total glutathione (GSH) levels were also found in pyrene‐exposed rats. We further observed that mRNA levels of several hepatic metabolizing enzymes regulated by constitutive androstane receptor (CAR) such as CYP2B1 and CYP2B2 significantly increased in pyrene‐exposed rats. These results suggest that decreased GSH levels, elevated hepatic metabolizing enzyme gene expression, and CAR activation are important contributors for pyrene‐induced hepatotoxicity in rats. Additionally, we found pyrene significantly induced plasma inflammatory indices including white blood cell and lymphocyte counts. We also observed that pyrene exposure increased relative weight of kidneys and disrupted kidney function with elevated urea and creatinine levels in rats.

show abstract

Selective induction of hepatic cytochrome P450 2B activity by leelamine in vivo, as a potent novel inducer

et al. 2014

View full text Add to dashboard Cite

Cytochrome P450 (CYP) is an important enzyme that can act on xenobiotic substances such as toxic chemicals or drugs. Phenobarbital (PB) has been widely used to induce CYP2B activity to investigate the drug-drug interaction of CYP2B substrate drugs. Leelamine is a diterpene compound, and is the current focus of efforts to develop a treatment for diabetes. In this study, we identified the selective and potent inductive effect of leelamine on CYP2B at doses of 5, 10, or 20 mg/kg in male ICR mice for 1 or 3 days. In liver, the activity of CYP2B significantly increased 3.6-fold after treatment with leelamine, compared to vehicle-treated group. Activities of benzyloxyresorufin O-dealkylase and pentoxyresorufin O-dealkylase significantly increased 6.3- and 5.3-fold, respectively, with a single treatment of 20 mg/kg leelamine for 1 day. Furthermore, immunoblot analysis showed that significantly and dose-dependently increased CYP2B10 protein levels in liver. However, PCR results showed that there were no significant changes in the CAR and CYP2B mRNA levels after leelamine treatment. Accordingly, we suggest that leelamine is a novel substitute of PB for the selective induction of CYP2B activity in vivo.

show abstract

CAR expression and inducibility of CYP2B genes in liver of rats treated with PB-like inducers

Cited by 17 publications

References 28 publications

Species-specific induction of CYP2B by 2,4,6-tryphenyldioxane-1,3 (TPD)

Species-specific induction of CYP2B by 2,4,6-tryphenyldioxane-1,3 (TPD)

Identification of hepatotoxicity and renal dysfunction of pyrene in adult male rats

Selective induction of hepatic cytochrome P450 2B activity by leelamine in vivo, as a potent novel inducer

Contact Info

Product

Resources

About