Comparative studies of the effects on liver and liver microsomal drug-metabolizing enzyme system by the fungicides captan, captafol and folpet in rats.

Comparative studies of the effects on liver and liver microsomal drug-metabolizing enzyme system by the fungicides captan, captafol and folpet in rats.
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杀菌剂克菌丹、敌菌丹、灭菌丹对大鼠肝脏及肝微粒体药物代谢酶系统影响的比较研究

DOI:
10.1111/j.1600-0773.1990.tb00739.x
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发表时间:
1990
期刊:
Pharmacology & toxicology
影响因子:
--
通讯作者:
Mutinga,ML
Mutinga,ML
中科院分区:
--
文献类型:
--
作者:
Dalvi,RR;Mutinga,ML

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结构相关的杀真菌剂克菌丹(captan)、克菌丹(captafol)和灭菌丹(folpet)是广泛用于控制种子、水果和蔬菜作物的各种真菌病害的广谱、非持久性杀真菌剂。对克菌丹、captafol和灭菌丹在大鼠中的口服LD 5 O值进行比较,结果表明captafol的毒性大于克菌丹和灭菌丹。在生物化学方面,克菌丹可干扰钙代谢、解偶联氧化磷酸化并抑制微粒体和溶酶体酶以及肝核DNA聚合酶(纳尔逊1971; Dillwith 1980; Urbanek-Karlowska 1980; Dalvi 1989)。然而,除了抑制真菌生长外,对captafol和灭菌丹的生化作用知之甚少。因此,在大鼠中进行了以下研究,以比较这些杀真菌剂对肝脏和肝脏单加氧酶的体内生化作用。克菌丹,纯度89%,购自美国加利福尼亚州里士满的Stauffer Chemical Company,工业级,captafol和灭菌丹葡萄糖-6-磷酸、葡萄糖-6-磷酸脱氢酶和烟酰胺腺嘌呤二核苷酸磷酸购自Boehringer曼海姆Corporation(Indianapolis,IN,USA),并用于制备NADPH生成系统。细胞色素C(来自马心脏的VI型,9100%纯度)从Sigma Chemical Company,St. Louis,MO,USA获得SDH、ALT和AST试剂盒也从Sigma Chemical Company,St. Louis,MO,USA获得。这些研究中使用的所有其他化学品都是分析级或试剂级的。在这些研究中使用体重为200-250 g的雄性Sprague道利大鼠。将它们饲养在温度控制室(25”)中的标准不锈钢笼中,12小时光-暗循环,并允许自由接触水和Purina大鼠食物。(Mazola Brand),并以20 mg/kg体重的剂量水平腹膜内注射克菌丹和灭菌丹,captafol为5 mg/kg体重。对照组仅注射玉米油(2 ml油/kg体重)。在另一项测定对照动物和处理动物睡眠时间的研究中,在用三种杀真菌剂处理后24小时腹膜内注射戊巴比妥(50 mg/kg),
Structurally related fungicides, captan, captafol and folpet are broad-spectrum, non-persistent fungicides widely used for the control of various fungus diseases of seeds, fruits and vegetable crops. A comparison of the oral LD5O values of captan, captafol and folpet in rats shows that captafol is more toxic than captan and folpet. Biochemically, captan disturbs calcium metabolism, uncouples oxidative phosphorylation and inhibits microsomal and lysosomal enzymes as well as DNA polymerase of liver nuclei (Nelson 1971; Dillwith 1980; Urbanek-Karlowska 1980; Dalvi 1989). However, not much is known about the biochemical effects of captafol and folpet other than they inhibit fungal growth. The following studies were therefore carried out in rats to compare the in vivo biochemical effects of these fungicides on liver and liver monooxygenases. Captan, 89% purity, was obtained from Stauffer Chemical Company, Richmond, CA, USA Technical grade, captafol and folpet (89% purity), were obtained from Chevron Chemical Company, San Francisco, CA, USA Glucose-6-phosphate, glucose-6-phosphate dehydrogenase and nicotinamide adenine dinucleotide phosphate were purchased from Boehringer Mannheim Corporation (Indianapolis, IN, USA) and were used to prepare the NADPH-generating system. Cytochrome C,(Type VI from horse heart, 9SlOO% purity) was obtained from Sigma Chemical Company, St. Louis, MO, USA SDH, ALT and AST kits were also obtained from Sigma Chemical Company, St. Louis, MO, USA All other chemicals used in these studies were of analytical or reagent grade. Male Sprague Dawley rats weighing 200-250 g were used in these studies. They were housed in standard stainless steel cages in a temperature-controlled room (25") on a 12-hr light-dark cycle and were allowed free access to water and Purina rat chow.Captan, captafol and folpet were suspended in corn oil (Mazola Brand) using a tissue grinder and vortex, and were injected intraperitoneally at a dosage level of 20 mg/kg body weight for captan and folpet, and 5 mg/kg body weight for captafol. The control group was injected with corn oil (2 ml oil/kg body weight) alone. In a separate study to determine sleeping time in the control and treated animals, pentobarbital (50 mg/kg) was injected intraperitoneally 24 hr following treatment with the three fungicides, and the sleeping time