AI Article Synopsis

  • * The study aimed to identify the reactive metabolites of IPC, understand which cytochrome P450 enzymes participate in its metabolism, and explore the relationship between metabolic activation and cytotoxicity.
  • * Results showed that IPC is metabolized into reactive forms that can damage liver cells, and using ketoconazole to inhibit certain enzymes reduced the liver cells' sensitivity to IPC's toxic effects.

Article Abstract

Isoprocarb (IPC), one of the most important carbamate pesticides, is used to control pests, such as rice planthoppers in crops. Studies have found that IPC induced hepatotoxicity in poultry chicken. However, the mechanisms of IPC-induced hepatotoxicity are unclear. The objectives of this study were to characterize reactive metabolites of IPC and , to identify cytochrome P450 enzymes for metabolic activation, and to define a possible correlation between the metabolic activation and cytotoxicity of IPC. In GSH- or NAC-supplemented microsomal incubations, one GSH conjugate (M6) and two NAC conjugates (M7 and M8) were detected after exposure to IPC. The corresponding GSH conjugate and NAC conjugates were found in the liver homogenates and urine of mice after IPC administration. IPC was found to be metabolized to a quinone intermediate reactive to GSH and . IPC was found to induce marked cytotoxicity in cultured mouse primary hepatocytes. Ketoconazole, a selective CYP3A4/5 enzyme inhibitor, attenuated the susceptibility of hepatocytes to IPC cytotoxicity.

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Source
http://dx.doi.org/10.1021/acs.jafc.2c07206DOI Listing

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