Gupta R C, Kadel W L
Breathitt Veterinary Center, Murray State University, Hopkinsville, KY 42240.
J Toxicol Environ Health. 1989;26(4):447-57. doi: 10.1080/15287398909531268.
Pretreatment of rats with the nonspecific esterase inhibitor iso-OMPA (1 mg/kg sc) 1 h prior to carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl N-methylcarbamate, 0.5 mg/kg sc) administration potentiated carbofuran toxicity by more than threefold. Neither iso-OMPA nor carbofuran in the given doses produced any gross toxic signs. Rats receiving combined treatment, however, showed severe hypercholinergic signs (salivation, tremors, muscle fasciculations, and convulsions) within 5-10 min following carbofuran administration, and the severity was comparatively greater than that observed with an acute dose of carbofuran (1.5 mg/kg sc). Rats pretreated with iso-OMPA (0.5 mg/kg) died within 10-15 min following the acute dose of carbofuran (1.5 mg/kg). Each drug when given alone (1.0 mg/kg iso-OMPA, 0.5 mg/kg carbofuran) caused a significant (p less than .01) inhibition of carboxylesterase (CarbE) activity in brain structures (cortex, stem, striatum, and hippocampus), skeletal muscle (hemidiaphragm), liver, and plasma, whereas acetylcholinesterase (AChE) activity remained significantly (p greater than .01) unchanged. The maximal CarbE inactivation in plasma (less than 14% remaining activity) following either drug indicated a tremendous nonspecific binding to non-AChE serine-containing enzymes. iso-OMPA pretreatment markedly potentiated carbofuran's anticholinesterase activity both in neuronal and in nonneuronal tissues. It can be concluded that iso-OMPA pretreatment potentiates carbofuran toxicity either by preventing nonspecific binding of carbofuran to CarbE and/or possibly by inhibiting its detoxification.
在给大鼠皮下注射呋喃丹（2,3 - 二氢 - 2,2 - 二甲基 - 7 - 苯并呋喃基N - 甲基氨基甲酸酯，0.5mg/kg）前1小时，用非特异性酯酶抑制剂异稻瘟净（1mg/kg皮下注射）对大鼠进行预处理，可使呋喃丹毒性增强三倍以上。给定剂量的异稻瘟净和呋喃丹均未产生任何明显的中毒症状。然而，接受联合治疗的大鼠在注射呋喃丹后5 - 10分钟内出现严重的胆碱能亢进症状（流涎、震颤、肌肉抽搐和惊厥），且严重程度比急性剂量的呋喃丹（1.5mg/kg皮下注射）所观察到的情况相对更严重。用异稻瘟净（0.5mg/kg）预处理的大鼠在急性剂量的呋喃丹（1.5mg/kg）注射后10 - 15分钟内死亡。单独给予每种药物（1.0mg/kg异稻瘟净，0.5mg/kg呋喃丹）时，会显著（p小于0.01）抑制脑结构（皮层、脑干、纹状体和海马体）、骨骼肌（半膈肌）、肝脏和血浆中的羧酸酯酶（CarbE）活性，而乙酰胆碱酯酶（AChE）活性则显著（p大于0.01）保持不变。两种药物注射后血浆中CarbE的最大失活（剩余活性小于14%）表明其与非AChE含丝氨酸酶有大量非特异性结合。异稻瘟净预处理显著增强了呋喃丹在神经元和非神经元组织中的抗胆碱酯酶活性。可以得出结论，异稻瘟净预处理增强呋喃丹毒性，要么是通过阻止呋喃丹与CarbE的非特异性结合，和/或可能是通过抑制其解毒作用。
