L-Methionine suppresses pathological sequelae of cis-platinum in the rat

Abstract

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.