Role of metabolism in parathion-induced hepatotoxicity and immunotoxicity.
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.
Kim
Dae Ok
DO
College of Pharmacy, Yeungnam University, Kyungsan, South Korea.
Lee
Sang Kyu
SK
Jeon
Tae Won
TW
Jin
Chun Hua
CH
Hyun
Sun Hee
SH
Kim
Eun Jung
EJ
Moon
Gui Im
GI
Kim
Jung-Ae
JA
Lee
Eung Seok
ES
Lee
Byung Mu
BM
Jeong
Hye Gwang
HG
Jeong
Tae Cheon
TC
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
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