Gailis L
Res Commun Chem Pathol Pharmacol. 1986 Sep;53(3):319-30.
Chlorpromazine increases the sensitivity of cells to doxorubicin; in vivo it also produces hypothermia, which has the contrary effect. To determine the net effect of these factors, we tested the toxicity of doxorubicin in mice which had developed chlorpromazine-induced hypothermia. Groups of 10 female Swiss albino mice received chlorpromazine (5 mg/kg sc). One hour later, when rectal temperature was 30 degrees C, doxorubicin. HCl (20 mg/kg ip) was injected. Median survival time was 10 +/- 2 days for controls and 48 +/- 5 days for chlorpromazine treated mice (4 experiments each). A high chlorpromazine dose (100 mg/kg) did not protect. Chlorpromazine (5 mg/kg) also reversed the slowing of weight gain by 5 mg/kg doxorubicin. If the drop in rectal temperature was prevented by keeping the mice at 32-35 degrees C, the protection by chlorpromazine was abolished. The results show that chlorpromazine protects against the toxicity of ip doxorubicin; the hypothermia produced by chlorpromazine seems to be essential for the protection.
氯丙嗪可增加细胞对阿霉素的敏感性；在体内它还会引起体温过低，而这具有相反的作用。为了确定这些因素的净效应，我们在已出现氯丙嗪诱导性体温过低的小鼠中测试了阿霉素的毒性。将10只雌性瑞士白化小鼠分为一组，给予氯丙嗪（5毫克/千克，皮下注射）。一小时后，当直肠温度为30摄氏度时，注射盐酸阿霉素（20毫克/千克，腹腔注射）。对照组的中位生存时间为10±2天，氯丙嗪处理组小鼠的中位生存时间为48±5天（各进行4次实验）。高剂量氯丙嗪（100毫克/千克）没有保护作用。氯丙嗪（5毫克/千克）还逆转了5毫克/千克阿霉素导致的体重增加减缓。如果通过将小鼠置于32 - 35摄氏度来防止直肠温度下降，氯丙嗪的保护作用就会消失。结果表明，氯丙嗪可保护小鼠免受腹腔注射阿霉素的毒性作用；氯丙嗪产生的体温过低似乎对这种保护作用至关重要。
