Binding of Toxic Substances and Suppression of Their Toxicities by Albumin

－Studies on Psychosine and Pentachlorophenol－

Abstract

Psychosine (galactosylsphingosine) potently inhibits cytochrome c oxidase (COX) activity and hemolyzes washed erythrocytes in vitro. However, no hemolytic anemia is seen in patients with Krabbe disease or its animal models in which a psychosine-degrading enzyme is missing. This "discrepancy" may be caused by albumin because, 1) albumin is synthesized only in liver and it does not enter cells once it is released into the blood stream; 2) albumin can bind psychosine and suppress its effects effectively; 3) psychosine cannot exert its toxicity in the blood, should it be present there. On the other hand, an artificial substance, pentachlorophenol (PCP), which is widely used for wood preservation, causes mitochondrial dysfunction and hemolysis in vitro, both of which can be suppressed by albumin. Hence, it appears reasonable that hemolytic anemia is extremely rare, and that a dramatic improvement was seen in patients severely intoxicated with PCP. Thus, differences in the effects of these toxins seen in vitro and in vivo seem to be well explained by the effects of albumin. These also suggest that attention to the possible effects of albumin may be rewarding in monitoring and treating some intoxications.