Basinger M A, Jones M M, Holscher M A
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235.
Fundam Appl Toxicol. 1990 Apr;14(3):568-77. doi: 10.1016/0272-0590(90)90261-h.
The pathological changes characteristically observed in the kidney, bone marrow, thymus, spleen, and duodenum of the rat given 12.2 mg/kg of cis-platinum (CDDP) ip are reduced or eliminated when a CDDP solution containing a 20-fold excess of L-methionine to cis-platinum is administered. L-Methionine was also effective in reducing the renal toxicity induced by CDDP when given orally 20 min before the iv administration of 7.5 mg CDDP/kg. L-Methionine did not compromise the efficacy of CDDP when the antitumor activity of the combination of L-methionine and CDDP was measured against the Walker 256 carcinosarcoma in the rat. No significant reduction in the antitumor activity of the CDDP resulted from the parenteral administration of L-Methionine when evaluated against the L1210 murine leukemia. The oral administration of L-methionine (500 mg/kg) 30 min after the administration of CDDP has no significant effect on the antitumor activity of CDDP in mice bearing the L1210 murine leukemia. The results suggest that L-methionine may have some practical utility in the control of certain aspects of CDDP toxicity.
当给予腹腔注射12.2毫克/千克顺铂(CDDP)的大鼠含有比顺铂过量20倍的L-蛋氨酸的CDDP溶液时,在其肾脏、骨髓、胸腺、脾脏和十二指肠中典型观察到的病理变化会减轻或消除。当在静脉注射7.5毫克/千克CDDP前20分钟口服L-蛋氨酸时,它也能有效减轻CDDP诱导的肾毒性。当测定L-蛋氨酸与CDDP联合对大鼠Walker 256癌肉瘤的抗肿瘤活性时,L-蛋氨酸不会损害CDDP的疗效。当针对L1210小鼠白血病进行评估时,肠胃外给予L-蛋氨酸不会导致CDDP的抗肿瘤活性显著降低。在给予CDDP 30分钟后口服L-蛋氨酸(500毫克/千克)对患有L1210小鼠白血病的小鼠中CDDP的抗肿瘤活性没有显著影响。结果表明,L-蛋氨酸在控制CDDP毒性的某些方面可能具有一定的实际用途。