Yamano T, Morita S
Osaka City Institute of Public Health and Environmental Sciences, Japan.
Arch Environ Contam Toxicol. 1995 Jan;28(1):1-7. doi: 10.1007/BF00213961.
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, beta-endosulfan and metalaxyl, had essentially no effects on any parameters tested at 10(-3) M.
对22种农药进行了体外实验，研究它们对从雄性大鼠分离出的肝细胞、线粒体和微粒体的影响。12种农药在浓度为10⁻³ M时，可使肝细胞中的非蛋白巯基（NPSH）含量降至对照值的80%以下。百菌清和福美锌尤为有效，在孵育90分钟后，10⁻⁴ M浓度时即可降低NPSH含量。在这些农药中，只有对苯二甲酸铜和百菌清分别与谷胱甘肽发生非酶促和酶促反应。四种农药，即百菌清、丙草胺、灭线磷和嗪草酮在10⁻³ - 10⁻⁴ M浓度时可刺激肝细胞中的脂质过氧化。用百菌清、敌百虫酰胺和福美锌孵育后，细胞活力显著降低。敌百虫酰胺的肝毒性被认为与其对线粒体能量产生的直接不良影响有关，因为它在10⁻⁶ M时可使分离的线粒体呼吸解偶联，并在细胞死亡前耗尽细胞ATP含量。相反，百菌清和福美锌诱导的肝毒性似乎与其对细胞巯基的消耗作用有关，因为向肝细胞孵育混合物中添加硫醇化合物二硫苏糖醇可保护细胞。关于分离的线粒体呼吸，四种农药在10⁻³ - 10⁻⁴ M浓度时抑制状态3和/或状态4的呼吸速率，而七种农药在10⁻³ - 10⁻⁶ M浓度时使状态4的呼吸解偶联。关于分离的微粒体脂质过氧化，三种农药在10⁻³ - 10⁻⁴ M浓度时具有过氧化作用，而三种农药在10⁻³ - 10⁻⁷ M浓度时具有抗氧化作用。只有两种农药，即β-硫丹和甲霜灵，在10⁻³ M浓度时对所测试的任何参数基本没有影响。
