Shiraishi N, Uno H, Waalkes M P
Inorganic Carcinogenesis Section, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201.
Toxicology. 1993 Dec 31;85(2-3):85-100. doi: 10.1016/0300-483x(93)90034-p.
Some studies have indicated that cadmium-induced lethality and selective injurious effects to specific tissues, such as testes or liver, can be prevented by pretreatment with the antioxidant L-ascorbic acid (ascorbic acid). However, the basis of this tolerance is unclear. We examined the effects of ascorbic acid pretreatment on cadmium toxicity in male Fischer (F344/NCr) rats. Cadmium treatment alone (25 mumol CdCl2/kg, s.c.) proved lethal, causing a 93% mortality within 72 h, but in rats pretreated with ascorbic acid (2 g/kg, s.c. 24, 12 and 1 h) cadmium-induced lethality was nearly prevented. Hepatic lesions, including hepatocellular necrosis, induced by cadmium were at least partially ameliorated by ascorbic acid pretreatment. Ascorbic acid pretreatment had no effect on cadmium-induced testicular lesions nor on cadmium content in testes, liver, kidney and urine. Ascorbic acid alone modestly increased hepatic metallothionein (MT), but not renal MT and had no effect on induction of hepatic or renal MT by cadmium. In contrast to liver and kidney, testicular cadmium-binding protein (TCBP) in rats exposed to cadmium alone decreased markedly. Moreover, the level of TCBP decreased unexpectedly in ascorbic acid pretreated rats as compared with control. These results indicate that ascorbic acid pretreatment decreases the toxicity of cadmium in the rat without markedly modifying its toxicokinetics or markedly stimulating MT synthesis.
一些研究表明，镉诱导的致死性以及对特定组织（如睾丸或肝脏）的选择性损伤作用可通过抗氧化剂L-抗坏血酸（维生素C）预处理来预防。然而，这种耐受性的基础尚不清楚。我们研究了抗坏血酸预处理对雄性Fischer（F344/NCr）大鼠镉毒性的影响。单独给予镉处理（25 μmol CdCl2/kg，皮下注射）被证明是致死性的，在72小时内导致93%的死亡率，但在预先用抗坏血酸（2 g/kg，皮下注射，分别在24小时、12小时和1小时）处理的大鼠中，镉诱导的致死性几乎得到预防。镉诱导的肝脏病变，包括肝细胞坏死，通过抗坏血酸预处理至少部分得到改善。抗坏血酸预处理对镉诱导的睾丸病变以及睾丸、肝脏、肾脏和尿液中的镉含量没有影响。单独使用抗坏血酸适度增加了肝脏金属硫蛋白（MT），但对肾脏MT没有影响，并且对镉诱导的肝脏或肾脏MT的诱导没有作用。与肝脏和肾脏不同，单独暴露于镉的大鼠睾丸镉结合蛋白（TCBP）明显降低。此外，与对照组相比，抗坏血酸预处理的大鼠中TCBP水平意外降低。这些结果表明，抗坏血酸预处理降低了大鼠体内镉的毒性，而没有明显改变其毒代动力学或明显刺激MT合成。
