Shimada H, Bare R M, Hochadel J F, Waalkes M P
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201, USA.
Toxicology. 1997 Jan 15;116(1-3):183-91. doi: 10.1016/s0300-483x(96)03544-5.
Previous work has indicated that testosterone pretreatment protects against cadmium-induced toxicity in male rats while other data indicate that pretreatment of mice with testosterone offers no such protection against cadmium. Since cadmium toxicity may vary widely with species and strain, we examined the effect of testosterone pretreatment on cadmium toxicity in two strains of mice, one that is sensitive (C3H) and one that is resistant (C57) to cadmium toxicity. A single sc injection of 20 micromol CdCl2/kg to C3H mice or 45 micromol CdCl2/kg to C57 mice proved very toxic, causing 50%, and 44% mortalities, respectively. However, when C57 mice were pretreated with testosterone (5 mg/kg, s.c., at - 48, - 24, and 0 h) prior to cadmium (45 micromol/kg), complete resistance to cadmium-induced lethality developed. Testosterone had no effect on cadmium-induced lethality in C3H mice. Testosterone prevented extensive hepatocellular damage caused by cadmium in C57 mice and also significantly reduced cadmium-induced elevations in serum lactate dehydrogenase (LDH) activity and blood urea nitrogen (BUN), which are indicators of hepatic and renal function, respectively. The toxicokinetics of cadmium were apparently not affected by testosterone pretreatment, as the distribution of cadmium to liver in either strain was unchanged by the steroid. Cadmium-induced metallothionein (MT) levels in liver and kidney of C57 mice were increased in testosterone-pretreated mice given the higher doses of metal but no such enhancement of MT synthesis occurred in C3H mice. This increase in MT may provide some level of protection against cadmium toxicity in the C57 mice. These results indicate that testosterone pretreatment prevents toxicity of cadmium in male C57 mice, possibly through enhancement of MT synthesis, but has no effect in male C3H mice.
先前的研究表明，睾酮预处理可保护雄性大鼠免受镉诱导的毒性，而其他数据表明，用睾酮预处理小鼠对镉并无此类保护作用。由于镉毒性可能因物种和品系的不同而有很大差异，我们研究了睾酮预处理对两种品系小鼠镉毒性的影响，一种对镉敏感（C3H），另一种对镉具有抗性（C57）。对C3H小鼠单次皮下注射20微摩尔/千克氯化镉或对C57小鼠单次皮下注射45微摩尔/千克氯化镉毒性极大，分别导致50%和44%的死亡率。然而，当C57小鼠在注射镉（45微摩尔/千克）之前用睾酮（5毫克/千克，皮下注射，在-48、-24和0小时）预处理时，对镉诱导的致死性产生了完全抗性。睾酮对C3H小鼠镉诱导的致死性没有影响。睾酮可防止C57小鼠因镉引起的广泛肝细胞损伤，还显著降低了镉诱导的血清乳酸脱氢酶（LDH）活性升高和血尿素氮（BUN）升高，这两者分别是肝功能和肾功能的指标。镉的毒代动力学显然不受睾酮预处理的影响，因为两种品系中镉在肝脏中的分布均未因该类固醇而改变。在给予较高剂量金属的睾酮预处理的C57小鼠中，镉诱导的肝脏和肾脏中金属硫蛋白（MT）水平升高，但在C3H小鼠中未发生MT合成增强。MT的这种增加可能为C57小鼠提供一定程度的抗镉毒性保护。这些结果表明，睾酮预处理可预防雄性C57小鼠的镉毒性，可能是通过增强MT合成，但对雄性C3H小鼠没有影响。
