Ishikawa M, Takayanagi Y, Sasaki K
Department of Pharmacology and Toxicology, Tohoku College of Pharmacy, Sendai, Japan.
Pharmacol Toxicol. 1991 May;68(5):366-70. doi: 10.1111/j.1600-0773.1991.tb01254.x.
To determine whether bacterial endotoxin (lipopolysaccharide, LPS from Escherichia coli) could modulate the lethality of cisplatin (CDDP) in mice, animals were treated with LPS (1 mg/kg, intraperitoneally) 24 hr and 1 hr before administration of cisplatin. A 1.6-fold increase in 8-day cumulative mortality was observed in LPS-treated mice compared to the mortality of those injected with saline before CDDP administration. The duration of previous exposure time to LPS appeared to be an important determinant of the potentiating effect, as many more mice died after 24 hr pretreatment than after 1 hr. Because renal toxicity remains a serious limitation to the effective use of CDDP, we determined whether LPS could also enhance CDDP-induced renal injury. CDDP markedly induces an increase in blood urea nitrogen (BUN) levels in LPS-treated mice. Treatment with LPS did not affect urinary excretion or renal tissue levels of total platinum, or the plasma pharmacokinetics of free and total platinum. Despite the potentiating effect of LPS on CDDP-induced lethality, it appeared that LPS can provide some enhancement of kidney function, because pretreatment of LPS enhanced an increase in BUN values.
为了确定细菌内毒素（脂多糖，来自大肠杆菌的LPS）是否能够调节顺铂（CDDP）对小鼠的致死性，在给予顺铂前24小时和1小时，给动物腹腔注射LPS（1mg/kg）。与在给予CDDP前注射生理盐水的小鼠死亡率相比，观察到LPS处理的小鼠8天累积死亡率增加了1.6倍。先前暴露于LPS的时间似乎是增强作用的一个重要决定因素，因为24小时预处理后死亡的小鼠比1小时预处理后多得多。由于肾毒性仍然是有效使用CDDP的严重限制，我们确定LPS是否也能增强CDDP诱导的肾损伤。CDDP显著诱导LPS处理的小鼠血尿素氮（BUN）水平升高。LPS处理不影响尿排泄或肾组织中总铂水平，也不影响游离铂和总铂的血浆药代动力学。尽管LPS对CDDP诱导的致死性有增强作用，但似乎LPS可以在一定程度上改善肾功能，因为LPS预处理增强了BUN值的升高。
