Detoxication of paraoxon by rat liver homogenate and serum carboxylesterases and A-esterases*

✍ Scribed by Jun Tang; Janice E. Chambers

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 119 KB
• Volume: 13
• Category: Article
• ISSN: 1095-6670
• DOI: 10.1002/(sici)1099-0461(1999)13:5<261::aid-jbt6>3.0.co;2-0

✦ Synopsis

Paraoxon, the active metabolite of parathion, can be detoxified through a noncatalytic pathway by carboxylesterases and a catalytic pathway by calcium-dependent A-esterases, producing p-nitrophenol as a common metabolite. The detoxication patterns of carboxylesterases and A-esterases were investigated in vitro in the present study with a high tissue concentration (75 mg/mL rat liver homogenate or 50% rat serum solution) to more closely reflect enzyme concentrations in intact tissues. A final paraoxon concentration of 3.75 lM was used to incubate with liver homogenates or serum solutions for 5 seconds or 3, 5, 15, or 25 minutes; also 0.625, 1.25, 2.5, 3.125, 3.75, or 5.0 lM paraoxon (final concentration) was incubated with liver homogenates or serum solutions for 15 minutes. Phenyl saligenin cyclic phosphate and EDTA were used to inhibit carboxylesterases and A-esterases, respectively. Significant amounts of p-nitrophenol were generated with or without either inhibitor during a 15 minute incubation with paraoxon from low (0.625 lM) to high (5.0 lM) concentrations. The amount of p-nitrophenol generated via carboxylesterase phosphorylation was greater than via A-esterase-mediated hydrolysis in the initial period of incubation or when