title: Role of metabolism in parathion-induced hepatotoxicity and immunotoxicity.
abstract: The objective of this study was to investigate whether metabolic activation of parathion by cytochrome P-450s (CYPs) was responsible for pesticide-induced hepatotoxicity and immunotoxicity. Initially, to investigate parathion metabolism in vitro, the production of paraoxon and p-nitrophenol, major metabolites of parathion, was determined by high-performance liquid chromatography (HPLC). Subsequently, metabolic fate and CYP enzymes involved in the metabolism of parathion were partially monitored in rat liver microsomes in the presence of the NADPH-generating system. Among others, phenobarbital (PB)-induced microsomes produced the metabolites paraoxon and p-nitrophenol to the greatest extent, indicating the involvement of CYP 2B in parathion metabolism. When female BALB/c mice were treated orally with 1, 4, or 16 mg/kg of parathion in corn oil once, parathion suppressed the antibody response to sheep red blood cells. To further investigate a possible role of metabolic activation by CYP enzymes in parathion-induced toxicity, female BALB/c mice were pretreated intraperitoneally with 40 mg/kg PB for 3 d, followed by a single oral treatment with 16 mg/kg parathion. PB pretreatment produced a decrease in hepatic glutathione content and increases in hepatotoxic paramenters in parathion-treated mice with no changes in the antibody response. In addition, greater p-nitrophenol amounts were produced when mice were pretreated with PB, compared to treatment with parathion alone. These results indicate that parathion-induced hepatotoxicity might be differentiated from immunotoxicity in mice.
authors.affiliation: College of Pharmacy, Yeungnam University, Kyungsan, South Korea.
authors.forename: Dae Ok
authors.initials: DO
authors.lastname: Kim
authors.forename: Sang Kyu
authors.initials: SK
authors.lastname: Lee
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Jeon
authors.forename: Chun Hua
authors.initials: CH
authors.lastname: Jin
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Hyun
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Kim
authors.forename: Gui Im
authors.initials: GI
authors.lastname: Moon
authors.forename: Jung-Ae
authors.initials: JA
authors.lastname: Kim
authors.forename: Eung Seok
authors.initials: ES
authors.lastname: Lee
authors.forename: Byung Mu
authors.initials: BM
authors.lastname: Lee
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects / Q000276:immunology; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001711:Biotransformation; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007306:Insecticides / Q000493:pharmacokinetics* / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009596:Nitrophenols / Q000378:metabolism; D010261:Paraoxon / Q000378:metabolism; D010278:Parathion / Q000493:pharmacokinetics* / Q000633:toxicity; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D007306:Insecticides; D009596:Nitrophenols; D010278:Parathion; D019362:Cytochrome P-450 CYP2B1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D010261:Paraoxon; C024836:4-nitrophenol; D010634:Phenobarbital