Baldew G S, van den Hamer C J, Los G, Vermeulen N P, de Goeij J J, McVie J G
Department of Radiochemistry, Interfaculty Reactor Institute, Delft, The Netherlands.
Cancer Res. 1989 Jun 1;49(11):3020-3.
The influence of selenium on cis-diamminedichloroplatinum(II) (c-DDP) nephrotoxicity in mice and rats was assessed, using single doses of both compounds. Sodium selenite, 2 mg of selenium per kg, given 1 h before c-DDP, greatly reduced blood urea nitrogen and creatinine levels and morphological kidney damage in both BALB/c mice and Wistar rats, while administration 1 h after c-DDP did not. Liver toxicity of selenium was evaluated by measuring serum glutamic pyruvate transaminase and serum glutamic oxalate transaminase and by routine histology. No liver damage was observed in animals treated with sodium selenite, 2 mg of selenium per kg, and physiological saline or c-DDP. Pretreatment with sodium selenite did not reduce the antitumor activity of c-DDP against MPC 11 plasmacytoma or Prima breast tumor in BALB/c mice. The present results indicate that sodium selenite may provide protection against c-DDP nephrotoxicity, when it is given before c-DDP. Moreover, selenium has an antineoplastic activity against several tumors. The combination of these qualities may open new perspectives in cancer chemotherapy.
使用单剂量的这两种化合物,评估了硒对小鼠和大鼠顺二氯二氨铂(II)(c-DDP)肾毒性的影响。在给予c-DDP前1小时给予每千克2毫克硒的亚硒酸钠,可显著降低BALB/c小鼠和Wistar大鼠的血尿素氮和肌酐水平以及肾脏形态学损伤,而在给予c-DDP后1小时给药则无此效果。通过测量血清谷丙转氨酶和血清谷草转氨酶以及常规组织学评估硒的肝毒性。在用每千克2毫克硒的亚硒酸钠、生理盐水或c-DDP处理的动物中未观察到肝损伤。亚硒酸钠预处理并未降低c-DDP对BALB/c小鼠MPC 11浆细胞瘤或Prima乳腺肿瘤的抗肿瘤活性。目前的结果表明,在给予c-DDP之前给予亚硒酸钠可预防c-DDP肾毒性。此外,硒对几种肿瘤具有抗肿瘤活性。这些特性的结合可能为癌症化疗开辟新的前景。