Interactions between dietary flavonoids and 2,3,7,8-tetrachlorodibenzo-p-dioxin on cytochromes P450 activity in a human intestinal model (Caco-2 cells)

Rats received various doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), Aroclor 1254 (ARO), beta-naphthoflavone (BNF) or phenobarbital (PB), and the hepatic expression of cytochromes P450IA1 and/or P450IIB1/IIB2 was analysed by immunohistochemistry and Western blotting. A clear heterogeneous acinar induction of IA1 was detected when a low dose of TCDD, ARO or BNF was administered. When a low dose of TCDD or ARO was administered, IA1 was found to be induced primarily in hepatocytes located in acinus zone 3, whereas when a low dose of BNF was administered, IA1 was found to be preferentially induced in hepatocytes located in acinus zone 1. A clear zonal induction of IIB1/IIB2 was also observed when a low dose of PB or ARO was administered. Both compounds induced IIB1/IIB2 preferentially in hepatocytes located in acinus zone 3. When rats were administered high doses of TCDD, ARO, BNF or PB there was no zonal pattern of induction of IA1 or IIB1/IIB2; instead, a pan-acinar induction of these enzymes was observed. These results indicate that the overall hepatic concentration of IA1 or IIB1/IIB2 is merely dependent on the proportion of ‘induced hepatocytes’ within the acinus, which in turn depends on the dose of the inducer.

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Impact of SARS‐CoV‐2 infection (COVID‐19) on cytochromes P450 activity assessed by the Geneva cocktail

Clinical Pharmacology & Therapeutics ◽

10.1002/cpt.2412 ◽

2021 ◽

Author(s):

Camille Lenoir ◽

Jean Terrier ◽

Yvonne Gloor ◽

François Curtin ◽

Victoria Rollason ◽

...

Keyword(s):

Cytochromes P450 ◽

P450 Activity

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Impact of acute inflammation on cytochromes P450 activity assessed by the Geneva Cocktail.

Clinical Pharmacology & Therapeutics ◽

10.1002/cpt.2146 ◽

2020 ◽

Author(s):

Camille Lenoir ◽

Youssef Daali ◽

Victoria Rollason ◽

François Curtin ◽

Yvonne Gloor ◽

...

Keyword(s):

Acute Inflammation ◽

Cytochromes P450 ◽

P450 Activity

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Personalized pharmacotherapy of arterial hypertension patients with musculoskeletal system diseases based on pharmacogenetic aspects

Pharmacogenetics and Pharmacogenomics ◽

10.37489/2588-0527-2021-1-24-32 ◽

2021 ◽

pp. 24-32

Author(s):

K. M. Muratov ◽

I. V. Stuk ◽

N. I. Lapudus

Keyword(s):

Current Issue ◽

Antihypertensive Drugs ◽

Musculoskeletal Diseases ◽

Cytochromes P450 ◽

Term Therapy ◽

Inflammatory Drugs ◽

Long Term Therapy ◽

A Current ◽

P450 Activity

Pharmacotherapy in patients with comorbidity is a current issue for clinical practice. Combination of hypertension and musculoskeletal diseases can be found in 40% of outpatients, which requires simultaneous administration of different drugs. The main mechanisms of drug interactions are associated with pharmacokinetics or pharmacodynamics alterations. It has been proven that changes in drugs pharmacokinetics can be due to cytochromes P450 activity. The main symptom of musculoskeletal diseases is chronic pain, which requires long-term therapy with non-steroidal anti-inflammatory drugs (NSAIDs). The 2C19 isoenzyme takes part in metabolism of some NSAIDs. Losartan, the inhibitor of renin-angiotensinaldosterone system (RAAS), is also metabolized by the 2C9 isoenzyme and is quite often prescribed to outpatients to treat hypertension. Hence, an influence of genetic factors on efficacy and safety of antihypertensive drugs and NSAIDs combinations requires further studies.

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Evaluation of P450 monooxygenase activity in lyophilized recombinant E. coli cells compared to resting cells

AMB Express ◽

10.1186/s13568-021-01319-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Thomas Hilberath ◽

Alessandra Raffaele ◽

Leonie M. Windeln ◽

Vlada B. Urlacher

Keyword(s):

Cytochromes P450 ◽

Rhodococcus Erythropolis ◽

Resting Cells ◽

P450 Monooxygenase ◽

Monooxygenase Activity ◽

Whole Cells ◽

E Coli ◽

Redox Partner ◽

Starting Point ◽

P450 Activity

AbstractCytochromes P450 catalyze oxidation of chemically diverse compounds and thus offer great potential for biocatalysis. Due to the complexity of these enzymes, their dependency of nicotinamide cofactors and redox partner proteins, recombinant microbial whole cells appear most appropriate for effective P450-mediated biocatalysis. However, some drawbacks exist that require individual solutions also when P450 whole-cell catalysts are used. Herein, we compared wet resting cells and lyophilized cells of recombinant E. coli regarding P450-catalyzed oxidation and found out that lyophilized cells are well-appropriate as P450-biocatalysts. E. coli harboring CYP105D from Streptomyces platensis DSM 40041 was used as model enzyme and testosterone as model substrate. Conversion was first enhanced by optimized handling of resting cells. Co-expression of the alcohol dehydrogenase from Rhodococcus erythropolis for cofactor regeneration did not affect P450 activity of wet resting cells (46% conversion) but was crucial to obtain sufficient P450 activity with lyophilized cells reaching a conversion of 72% under the same conditions. The use of recombinant lyophilized E. coli cells for P450 mediated oxidations is a promising starting point towards broader application of these enzymes.

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