Departmental Bulletin Paper Long-term p-nitrophenol exposure can disturb liver metabolic cytochrome P450 genes together with aryl hydrocarbon receptor in Japanese quail

Ahmed, Eman  ,  Nagaoka, Kentaro  ,  Fayez, Mostafa  ,  Samir, Haney  ,  Watanabe, Gen

63 ( 3 )  , pp.115 - 127 , 2015-08 , Graduate School of Veterinary Medicine, Hokkaido University
P-Nitrophenol is a major metabolite of some organophosphorus compounds. It is considered to be one of nitrophenol derivatives of diesel exhaust particles that induce substantial hazards impacts on human and animal health. P-Nitrophenol (PNP) is a persistent organic pollutant. Consequently, bioaccumulation of PNP potentiates toxicity. The objectives of the current study were to assess the potential hepatic toxicity and pathway associated with long-term exposure to PNP. Japanese quails were orally administered different doses of PNP for 75 days. Liver and plasma samples were collected at days 45 (45D), days 60 (60D) and days 75 (75D). Liver histological changes and plasma corticosterone levels were assessed. Basal mRNA level of cytochromes P450 (CYP 450) (CYP1A4, 1A5, 1B1), heme oxygenase (HO-1), and aryl hydrocarbon receptor 1 (AhR1), from the liver of exposed birds and primary hepatocytes cultured for 24 hr with PNP, were analyzed using quantitative real-time PCR. The results revealed various histopathological changes in the liver, such as lymphocytes aggregation and hepatocytes degeneration. Significant increases in corticosterone levels were reported. After 60-days of in vivo exposure, the birds exhibited an overexpression in the liver CYP1A4, 1B1, AhR1, and HO-1. Furthermore, with continuous PNP administration, an overall downregulation of the tested genes was observed. In vitro, although a significant overexpression of CYP1A4, 1B1, and HO-1 was observed, CYP1A5 was downregulated. In conclusion, PNP can interfere with the liver CYP 450 enzymes and modulate HO-1 expression in the in vitro and in vivo experiments. Hence, it could have serious deleterious effects on humans, livestock, and wild animals.

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