Phenobarbitone-Mediated Translocation of the Cytosolic Proteins Interacting with the 5′-Proximal Region of Rat Liver CYP2B1/B2 Gene into the Nucleus

Samudre, Kalpana; Mani, Sendurai A.; Vathsala, P G; Rangarajan, Pundi N.; Padmanaban, Govindarajan

doi:10.1006/bbrc.2002.6665

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…Our study demonstrated that EGb 761 treatment for 10 days markedly induced the activity and expression of rat CYP2B1/2. CYP2B1 and CYP2B2 are major PBinducible CYP enzymes in rat liver [85,86]. However, several CYPs such as CYP3A1/2 and 2C6 are also induced by PB treatment, although the amount of these isoforms has been shown to be smaller than that of CYP2B1/2 after PB treatment in rat liver [87,88].…”

Section: Discussionmentioning

confidence: 99%

Induction of Propranolol Metabolism by Ginkgo biloba Extract EGb 761 in Rats

Zhao¹,

Huang²,

Chen³

et al. 2006

CDM

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Ginkgo biloba is one of the most popular herbal medicines in the world, due to its purported pharmacological effects, including memory-enhancing, cognition-improving, and antiplatelet effects. When used in the elderly, Ginkgo has a high potential for interactions with cardiovascular drugs. This study aimed to investigate the effects of the standard Ginkgo biloba extract (EGB 761) treatment on the pharmacokinetics of propranolol and its metabolism to form Ndesisopropylpropranolol (NDP) in rats. We also examined the activity and expression of cytochrome P450 (CYP) 1A and other CYPs in rats treated with EGb 761 at 10 and 100 mg/kg/day for 10 days. A single oral dose of propranolol (10 mg/kg) was administered on day 11 and the concentrations of both propranolol and NDP were determined using validated liquid chromatography-mass spectrometry (LC-MS) methods. The levels of mRNA and protein of various CYPs were determined by RT-PCR and Western blotting analysis, respectively. Pretreatment of EGb 761 at 100 mg/kg, but not 10 mg/kg, for 10 days significantly reduced the area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C max ) of propranolol, whereas those values of NDP were significantly increased. CYP1A1, 1A2, 2B1/2, and 3A1 activities and gene expression in the rat liver were significantly increased in a dose-dependent manner by pretreatment with EGb 761. The ex-vivo formation of NDP in liver microsomes from rats pretreated with EGb 761 was markedly enhanced. The formation of NDP from propranolol in liver microsomes was significantly inhibited by α-naphthoflavone (ANF, a selective CYP1A2 inhibitor), but not by quinidine (a CYP2D inhibitor). These results indicated that EGb 761 pretreatment decreased the plasma concentrations of propranolol by accelerated conversion of parental drug to NDP due to induction of CYP1A2. EGb 761 pretreatment also significantly induced CYP2B1/2 and CYP3A1, suggesting potential interactions with substrate drugs for these two enzymes. Further study is needed to explore the potential for gingko-drug interactions and the clinical impact.

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Section: Discussionmentioning

confidence: 99%

Induction of Propranolol Metabolism by Ginkgo biloba Extract EGb 761 in Rats

Zhao¹,

Huang²,

Chen³

et al. 2006

CDM

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“…Members of the CYP2C (e.g., CYP2C9, 2C8, and 2C19) metabolize a large number of commonly used drugs such as fluoxetine, fluvastatin, diclofenac, diazepam, mephenytoin or omeprazole. CYP2 regulation by marine biotoxins was investigated in 23 different papers (Abe et al 2017 ; Alarcan et al 2017 ; Ferron et al 2016 ; Gahrs et al 2013 ; Ganem et al 1999 ; Honkakoski and Negishi 1998 ; Inoue et al 2006 ; Joannard et al 2000 ; Kawamoto et al 1999 ; Kawamura et al 1999 ; Morey et al 2008 ; Nirodi et al 1996 ; Posti et al 1999 ; Pustylnyak et al 2005 ; Samudre et al 2002 ; Sidhu and Omiecinski 1997 ; Swales et al 2005 ; Tohkin et al 1996 ; Wuerger et al 2022 , 2023 ; Yamasaki et al 2018 ; Yoshinari et al 2003 ; Zhang et al 2006 ), as summarized in Table 2 . Thus, CYP2 family members constitute the CYP enzymes which have been most often mentioned in the context of CYP regulation by marine biotoxins.…”

Section: Literature Search Strategymentioning

confidence: 99%

Effects of marine biotoxins on drug-metabolizing cytochrome P450 enzymes and their regulation in mammalian cells

Würger,

Alarcan,

Braeuning

2024

Arch Toxicol

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Marine biotoxins are a heterogenous group of natural toxins, which are able to trigger different types of toxicological responses in animals and humans. Health effects arising from exposure to marine biotoxins are ranging, for example, from gastrointestinal symptoms to neurological effects, depending on the individual toxin(s) ingested. Recent research has shown that the marine biotoxin okadaic acid (OA) can strongly diminish the expression of drug-metabolizing cytochrome P450 (CYP) enzymes in human liver cells by a mechanism involving proinflammatory signaling. By doing so, OA may interfere with the metabolic barrier function of liver and intestine, and thus alter the toxico- or pharmacokinetic properties of other compounds. Such effects of marine biotoxins on drug and xenobiotic metabolism have, however, not been much in the focus of research yet. In this review, we present the current knowledge on the effects of marine biotoxins on CYP enzymes in mammalian cells. In addition, the role of CYP-regulating nuclear receptors as well as inflammatory signaling in the regulation of CYPs by marine biotoxins is discussed. Strong evidence is available for effects of OA on CYP enzymes, along with information about possible molecular mechanisms. For other marine biotoxins, knowledge on effects on drug metabolism, however, is scarce.

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“…After PB treatment, increased binding of phosphorylated proteins to a positive element (Ϫ98 to Ϫ69 bp) in the CYP2B1/2 flanking region was observed in rat livers in vivo (Prabhu et al, 1995;Nirodi et al, 1996;Sultana et al, 1997). These proteins have eluded identification so far (Samudre et al, 2002). In contrast, in transgenic mice expressing either 800 bp or 19 kb of CYP2B2 flanking region, only the strain with the 19 kb showed responsiveness to PB (Ramsden et al, 1993(Ramsden et al, , 1999.…”

Section: Cyp2bs Cyp3as and Cyp2cs In Mammalsmentioning

confidence: 99%