Protective effects of neutral amino acids against amphipathic drug-induced hemolysis

Some neutral amino acids were compared for their anti-hemolytic effects with sugars which are well-known colloid-osmotic protectants. The kinetic studies in isotonic suspensions of erythrocytes indicated that the hemolysis induced by the amphipathic drug chlorpromazine (CPZ) or flufenamic acid (FA) was retarded by addition of sugars, and the degree of the anti-hemolytic effect increased with increases in molecular size. Phenylalanine (Phe), the largest among the amino acids tested, showed the greatest inhibitory effect on CPZ-induced hemolysis, but not on FA-induced hemolysis. This demonstrated that the anti-hemolytic effects of amino acids were not the result of colloid-osmotic protection. Hemolytic actions of amino acids were also examined to determine their interaction with the erythrocyte membrane, and the mechanism of their inhibitory effects against amphipathic drug-induced hemolysis was discussed.