Yang X F, Yang Y N
Institute of Applied Toxicology, Nanjing Medical University, China.
Biomed Environ Sci. 1997 Dec;10(4):402-7.
Protective effects of calcium antagonists, chlorpromazine (CPZ) and nimodepine (NI-MO), on cadmium-induced toxicity were investigated. After giving CdCl2 (0.44 mg Cd/kg, i.p.), CPZ (5 mg/kg, i.p.) or NIMO (8 mg/kg, p.o.) were administered every day to Sprague-Dawley (S.D.) rats for a week. Then, urinary N-acetyl-beta-D-glucosaminidase (NAG), urinary cadmium and blood cadmium were measured. The accumulation of cadmium in the kidney cortex, content of renal calmodulin, hemoglobin and the ultrastructural damage of proximal convoluted tubules of rats were examined three weeks after the last administration. Results indicated that the calcium antagonists partly protected against toxic effects induced by cadmium in different manners. These data provide further evidence for the new hypothesis that the cross effect of cadmium and calcium in calmodulin regulated systems may be responsible for the mechanism of cadmium intoxication. The results suggested that the calcium antagonists could be a new and promising approach in the therapy of heavy metal-induced diseases.
研究了钙拮抗剂、氯丙嗪（CPZ）和尼莫地平（NIMO）对镉诱导毒性的保护作用。给Sprague-Dawley（S.D.）大鼠腹腔注射氯化镉（0.44 mg镉/千克）后，每天腹腔注射CPZ（5 mg/千克）或口服NIMO（8 mg/千克），持续一周。然后，测定尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）、尿镉和血镉。在最后一次给药三周后，检测大鼠肾皮质中镉的蓄积、肾钙调蛋白含量、血红蛋白以及近端曲管的超微结构损伤。结果表明，钙拮抗剂以不同方式部分保护了镉诱导的毒性作用。这些数据为新假说提供了进一步证据，即钙调蛋白调节系统中镉和钙的交叉效应可能是镉中毒机制的原因。结果表明，钙拮抗剂可能是治疗重金属诱导疾病的一种新的有前景的方法。
