4-Nitrophenol (PNP) is used to manufacture drugs, fungicides and parathion insecticides, also it is one of four nitrophenols derivatives from DEP and consider as EDCs. It is known that PNP has various harmful physiological effects. This research was conducted to investigate the effect of chronic PNP exposure on liver health condition, 28 days-old male Japanese quail where orally administered PNP (0, 0.01, 0.1, 1mg/kg b.w) for 2.5 months where samples collected every 15 days and histopathology (H&E and PAS), PCNA, apoptosis detection and serum AST level were further used to study the impacts of PNP. Basal mRNA level of cytochrom P450 enzymes (CYP 1A4, 1A5, 1B1), Ho-1, GST and AH receptor from liver in vivo and in vitro from liver hepatocyte 24 h incubation with PNP at different concentration measured using RT-PCR method. Result showed that chronic P-nitrophenol exposure caused interruption in liver weight accompanied with histopathological signs i.e. lymphocytic aggregation, congestion of blood vessels, hepatocyte degeneration and necrosis at different degree and this reflected on the plasma hepatic enzymes concentrations (AST) where all over increase in AST specially at 2.5 months where mid dose reported 503.0 U/l and high dose 350.0 U/l versus to 204 U/l in control group also significant increase in PCNA (P<0.01), glycogen accumulation (P<0.05) and apoptotic cell (P<0.01) were reported. In vivo, after 2 months of PNP administration bird exhibit overexpression in CYP1A4(˜1.5-2fold higher), 1B1 enzyme(˜5-10 fold higher), AhR (˜ 2-4 fold higher)and HO-1 than other enzymes, GST and 1A5, which showed no change compared with value for control group but with continuous chronic PNP administration over all down-regulation in all liver tested genes reported. In vitro experiment showed significant overexpression of CYP1A4, HO-1, downregulation of CYP1A5, no change in CYP1B1 and finally Ah receptor not detected. From these result we can conclude that PNP has toxic effect on liver cell function and increase oxidative stress in vivo and in vitro which may be affect on the other organ systems.
Keywords: Cytochrom P450 enzymes, quail, PNP, oxidative stress, hepatocyte, Diesel exhaust particles (DEP), Aryl HR.
Air pollution considers as a grave problem all over the world (Li et al., 2006), and DEPs contributing to this situation, Exposure to DEP is an environmental and occupational health concern. 4-nitrophenol (PNP), C6H5NO3, and the molecular weight is 139.11 g/mol, is one of four nitrophenols derivatives from DEP(Noya et al., 2008), also a degeneration product of the organophosphorus insecticides i.e parathion (Kim et al., 2006) where a major detoxification pathway of methyl parathion is enzymatic hydrolysis of the toxic metabolite, methyl paraoxon, to dimethyl phosphate and 4-nitrophenol (Benke and Murphy 1975). 4-Nitrophenol is used to manufacture some drugs (e.g., acetaminophen), fungicides, insecticides (methyl and ethyl parathion),...