Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Life Sci. 2013 Apr 9;92(12):727-32. doi: 10.1016/j.lfs.2013.01.031. Epub 2013 Feb 9.
Cisplatin (CDDP) is a potent anticancer agent, but severe renal toxicity can limit its use. We investigated the protective effect of cepharanthin (CE), a biscoclaurin alkaloid, on the renal toxicity of CDDP.
Mice were given CDDP along with CE. Effects of CE on CDDP toxicity were investigated by assaying markers of renal toxicity together with MT expression, and by histopathological examination of the kidney. MT-null mice were also examined.
CE induced expression of metallothionein (MT). Pre-administration of CE attenuated an increase in blood urea nitrogen (BUN) concentrations after the CDDP injection. A histochemical analysis demonstrated protection against CDDP-induced necrocytosis of kidney tissues by CE. The protective effect of CE did not occur in the MT-null mice.
Pretreatment with CE may reduce the renal toxicity of CDDP through expression of MT.
顺铂（CDDP）是一种有效的抗癌药物，但严重的肾毒性限制了其应用。我们研究了双稠吡咯啶生物碱芹菜素（CE）对 CDDP 肾毒性的保护作用。
给小鼠同时给予 CDDP 和 CE。通过测定肾毒性标志物和 MT 表达，以及肾组织的组织病理学检查，研究 CE 对 CDDP 毒性的影响。还检查了 MT 缺失小鼠。
CE 诱导金属硫蛋白（MT）的表达。CE 的预先给药可减轻 CDDP 注射后血尿素氮（BUN）浓度的升高。组织化学分析表明，CE 可防止 CDDP 诱导的肾组织坏死。CE 的保护作用在 MT 缺失小鼠中没有发生。
CE 的预处理可能通过 MT 的表达来降低 CDDP 的肾毒性。
