Ohtaka K, Hamade N, Yamazaki Y, Suzuki M, Koizumi A
Department of Anesthesiology, Akita University School of Medicine, Japan.
Arch Toxicol. 1995;69(8):559-64. doi: 10.1007/s002040050212.
O,O,S-Trimethyl phosphorothioate (OOS-TMP) is known to induce unique symptoms, which are characterized by hypophagia, progressive weight loss, and hypothermia. To determine whether there is the possibility of a causal relationship between these toxic symptoms and a direct action of OOS-TMP on the central nervous system, we investigated the development of these symptoms in Fischer 344 female rats after oral or intracerebral treatment with OOS-TMP. Oral administration of OOS-TMP at 20 mg/kg induced marked hypophagia, progressive weight loss and hypothermia. Moreover, inhibition of respiratory rate was observed immediately after treatment. It lasts during the entire experimental period. Profound hypothermia below 34 degrees C was observed more frequently in the rats, which became hypercapnic (PaCO2 > or = 50 mmHg). In contrast, administration of OOS-TMP at 20 mg/kg (as much as the oral dose) into the cerebral lateral ventricle succeeded in inducing hypophagia, progressive weight loss and lowered respiratory rates. On the other hand, by this route of administration, OOS-TMP at 20 mg/kg failed to induce hypothermia, hypercapnia and lung injury. The present results suggest that hypophagia and inhibitions of respiratory rate are attributable to the direct action of OOS-TMP on the central nervous system, while other symptoms are associated with lung injury.
硫代磷酸O,O,S-三甲基酯（OOS-TMP）已知会引发独特症状，其特征为摄食减少、体重逐渐减轻和体温过低。为了确定这些毒性症状与OOS-TMP对中枢神经系统的直接作用之间是否存在因果关系，我们研究了用OOS-TMP对Fischer 344雌性大鼠进行口服或脑内给药后这些症状的发展情况。以20 mg/kg的剂量口服OOS-TMP会导致明显的摄食减少、体重逐渐减轻和体温过低。此外，给药后立即观察到呼吸频率受到抑制。这种抑制在整个实验期间持续存在。在出现高碳酸血症（动脉血二氧化碳分压≥50 mmHg）的大鼠中，更频繁地观察到体温低至34摄氏度以下的深度低温。相比之下，将20 mg/kg的OOS-TMP（与口服剂量相同）注入大脑侧脑室成功诱导了摄食减少、体重逐渐减轻和呼吸频率降低。另一方面，通过这种给药途径，20 mg/kg的OOS-TMP未能诱导体温过低、高碳酸血症和肺损伤。目前的结果表明，摄食减少和呼吸频率抑制归因于OOS-TMP对中枢神经系统的直接作用，而其他症状与肺损伤有关。
