Nitrophenols disrupt the expression and activity of biotransformation enzymes (CYP3A and COMT) in chicken ovarian follicles in vivo and in vitro

• Published in: Journal of applied toxicology Vol. 44; no. 5; pp. 756 - 769
• Main Authors: Kozubek, Anna, Katarzyńska‐Banasik, Dorota, Kowalik, Kinga, Grzegorzewska, Agnieszka K., Hrabia, Anna, Sechman, Andrzej
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.05.2024
• Subjects: Animals; Biotransformation; Chickens; Colorimetry; Cytochrome P-450 CYP3A - genetics; Cytochrome P-450 CYP3A - metabolism; Defence mechanisms; Detoxification; Diesel engines; Enzymes; Female; Follicles; Fumes; In vivo methods and tests; Nitrophenol; Nitrophenols - metabolism; Nitrophenols - toxicity; Nucleotide sequence; Ovarian Follicle - metabolism; Ovaries; Ovary; Pesticides; Poultry; Steroidogenesis; Theca; Toxicity tests; Xenobiotics
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.4573

Nitrophenols are environmental pollutants and xenobiotics, the main sources of which are diesel exhaust fumes and pesticides. The biotransformation processes that take place in the liver are defence mechanisms against xenobiotics, such as nitrophenols. Our previous study showed that the chicken ovary is an additional xenobiotic detoxification place and that nitrophenols disrupt steroidogenesis in chicken ovarian follicles. Therefore, the present study aimed to determine the in vivo and in vitro effects of 4‐nitrophenol (PNP) and 3‐methyl‐4‐nitrophenol (PNMC) on the expression and activity of phase I (CYP3A) and phase II (COMT) biotransformation enzymes in chicken ovary. In an in vivo study, hens were treated with a vehicle or 10 mg PNP or PNMC/kg b.wt. per day for 6 days. In an in vitro study, prehierarchical white and yellowish follicles, as well as the granulosa and theca layers of the three largest preovulatory follicles (F3, F2 and F1), were isolated and then incubated in a control medium or medium supplemented with PNP (10−6 M) or PNMC (10−6 M) for 24 or 48 h. Both in vivo and in vitro studies showed that nitrophenols exert tissue‐ and compound‐dependent (PNP or PNMC) effects on CYP3A and COMT gene (real‐time PCR) protein (Western blot) expression and their activity (colorimetric methods). The inhibitory effect of nitrophenols in vivo on the activity of biotransformation enzymes suggest that the ovary has the capacity to metabolise PNP and PNMC. This study aimed to determine the in vivo and in vitro effects of 4‐nitrophenol (PNP) and 3‐methyl‐4‐nitrophenol (PNMC) on the expression and activity of phase I (CYP3A) and phase II (COMT) biotransformation enzymes in chicken ovary. The results revealed that nitrophenols have a tissue‐ and compound‐dependent (PNP or PNMC) effect on CYP3A and COMT expression and activity, indicating that they can disrupt endogenous compounds and xenobiotic metabolism. Additionally, nitrophenols may lead to ovarian cancer by COMT inhibition.