Calmodulin inhibitors protect against cadmium-induced testicular damage in mice.
Calmodulin inhibitors protect against cadmium-induced testicular damage in mice.
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DOI：
10.1095/biolreprod37.1.127
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发表时间：
1987-08
影响因子：
3.6
通讯作者：
R. Niewenhuis;W. Prozialeck
中科院分区：
文献类型：
--
作者：
R. Niewenhuis;W. Prozialeck
最近的报道表明，镉可以与钙调蛋白相互作用并激活钙调蛋白敏感酶，这使得我们研究了钙调蛋白抑制剂对镉诱导的小鼠睾丸毒性的影响。用不同的钙调蛋白抑制剂或非活性类似物对雄性CF-1小鼠进行预处理，然后在1小时后给予Cd Cl2 X 2 1/2H2O(32mmoles/kg)。24小时后，处死小鼠，取出睾丸称重。通过测定睾丸匀浆中可溶部分在414 nm处的吸光度来量化出血的程度。暴露于Cd~(2+)使睾丸平均重量从118m g/-5m g增加到146m g，血红蛋白吸光度从0.096+/-0.006增加到0.767+/-0.138。预先给予钙调素抑制剂三氟拉嗪(40mmoles/kg)、氯丙嗪(40mmols/kg)或W-7(140mmoles/kg)可显著减轻镉诱导的上述两项指标的升高，而氯丙氨酸亚砜(140mmols/kg)、戊巴比妥钠(140mmols/kg)、异搏定(80mmoles/kg)或乙二胺四乙酸乙酯(140mumoles/kg)则无明显作用。这些结果表明，钙调蛋白抑制剂可以对抗镉的某些毒性效应，并与镉的某些效应可能是由于钙调素依赖的酶被不当激活所致的假说一致。
Recent reports showing that cadmium can interact with calmodulin and activate calmodulin-sensitive enzymes have lead us to examine the effects of calmodulin inhibitors on cadmium-induced testicular toxicity in mice. Male CF-1 mice were pretreated with the various calmodulin inhibitors or inactive analogs and then, one hour later, given CdCl2 X 2 1/2 H2O (32 mumoles/kg). After 24 hours, the mice were killed and the testes were removed and weighed. The extent of hemorrhaging was quantified by determining the absorbance of hemoglobin at 414 nm in the soluble fraction of testicular homogenates. Exposure to Cd2+ increased the mean testicular weight from 118 +/- 5 mg to 146 +/- 4 mg and the hemoglobin absorbance from 0.096 +/- 0.006 to 0.767 +/- 0.138. Pretreatment with the calmodulin inhibitors, trifluoperazine (40 mumoles/kg), chlorpromazine (40 mumoles/kg) or W-7 (140 mumoles/kg) greatly attenuated the CD2+-induced increase in both parameters, whereas pretreatment with chlorpromazine sulfoxide (140 mumoles/kg), pentobarbital (140 mumoles/kg), verapamil (80 mumoles/kg) or ethylenediaminetetraacetate (140 mumoles/kg) did not. These results indicate that calmodulin inhibitors can protect against certain toxic effects of cadmium and are consistent with the hypothesis that some of the effects of cadmium may result from the improper activation of calmodulin-dependent enzymes.