Effects of pesticides on isolated rat hepatocytes, mitochondria, and microsomes II

Abstract

Twenty-two pesticides were examined in vitro for their effects on hepatocytes, mitochondria, and microsomes isolated from male rats. Twelve pesticides reduced non-protein sulfhydryl (NPSH) content in hepatocytes to less than 80% of control at a concentration of 10⁻³ M. Chlorothalonil and ziram were especially effective, reducing NPSH content at 10⁻⁴ M after 90 min incubation. Among those pesticides, only copper terephthalate and chlorothalonil were reactive with glutathione non-enzymatically and enzymatically, respectively. Lipid peroxidation in hepatocytes was stimulated by four pesticides, namely, chlorothalonil, pretilachlor, ethoprofos, and metribuzin at 10⁻³–10⁻⁴ M. Cell viability was considerably decreased following incubation with chlorothalonil, trichlamide, and ziram. Hepatotoxicity of trichlamide was considered to be associated with its direct adverse effects on mitochondrial energy production, since it uncoupled isolated mitochondrial respiration at 10⁻⁶ M and depleted cellular ATP content prior to cell death. Conversely, chlorothalonil- and ziram-induced hepatotoxicity seemed to be related to their depleting effects on cellular sulfhydryls, since addition of the thiol compound dithiothreitol to the hepatocytes incubation mixture protected cells. With respect to isolated mitochondrial respiration, four pesticides inhibited state 3 and/or state 4 respiration rates at 10⁻³–10⁻⁴ M, whereas seven pesticides uncoupled state 4 respiration at 10⁻³–10⁻⁶ M. With respect to isolated microsomal lipid peroxidation, three pesticides were peroxidative at 10⁻³–10⁻⁴ M, whereas three pesticides were antioxidative at 10⁻³–10⁻⁷ M. Only two pesticides, β-endosulfan and metalaxyl, had essentially no effects on any parameters tested at 10⁻³ M.