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首页> 外文期刊>Archives of Toxicology >Sexual dimorphism of cadmium-induced toxicity in rats: involvement of sex hormones
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Sexual dimorphism of cadmium-induced toxicity in rats: involvement of sex hormones

机译：镉致大鼠毒性的性二态性：性激素的参与

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The toxic effect of cadmium varies with sex in experimental animals. Previous studies have demonstrated that pretreatment of male Fischer 344 (F344) rats with the female sex hormone progesterone markedly enhances the susceptibility to cadmium, suggesting a role for progesterone in the sexual dimorphism of cadmium toxicity. In the present study, we attempted to further elucidate the mechanism for sex differences in cadmium-induced toxicity in F344 rats. A single exposure to cadmium (5.0 mg Cd/kg, sc) was lethal in 10/10 (100 %) female compared with 6/10 (60 %) male rats. Using a lower dose of cadmium (3.0 mg Cd/kg), circulating alanine aminotransferase activity, indicative of hepatotoxicity, was highly elevated in the cadmium treated females but not in males. However, no gender-based differences occurred in the hepatic cadmium accumulation, metallothionein or glutathione levels. When cadmium (5.0 mg Cd/kg) was administered to young rats at 5 weeks of age, the sex-related difference in lethality was minimal. Furthermore, although ovariectomy blocked cadmium-induced lethality, the lethal effects of the metal were restored by pretreatment with progesterone (40 mg/kg, sc, 7 consecutive days) or β-estradiol (200 μg/kg, sc, 7 consecutive days) to ovariectomized rats. These results provide further evidence that female sex hormones such as progesterone and β-estradiol are involved in the sexual dimorphism of cadmium toxicity in rats.
机译：在实验动物中，镉的毒性作用随性别而变化。先前的研究表明，用雌性激素黄体酮对雄性Fischer 344（F344）大鼠进行预处理可显着提高对镉的敏感性，这表明孕酮在镉毒性的二态性中起作用。在本研究中，我们试图进一步阐明F344大鼠镉诱导的毒性中性别差异的机制。与6/10（60％）雄性大鼠相比，10/10（100％）雌性单次暴露于镉（5.0 mg Cd / kg，sc）致死。使用较低剂量的镉（3.0 mg Cd / kg），表明经肝毒性的循环丙氨酸氨基转移酶活性在经镉处理的雌性动物中高度升高，而在雄性动物中则没有。然而，在肝镉积累，金属硫蛋白或谷胱甘肽水平上没有基于性别的差异。当在5周龄时对年轻大鼠施用镉（5.0 mg Cd / kg）时，与性别相关的致死率差异很小。此外，尽管卵巢切除术阻止了镉诱导的致死性，但通过孕酮（40 mg / kg，皮下注射，连续7天）或β-雌二醇（200μg/ kg，皮下注射，连续7天）的预处理可以恢复金属的致死作用。去卵巢大鼠。这些结果提供了进一步的证据，证明雌性激素如孕酮和β-雌二醇参与了大鼠镉毒性的性二态性。

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