Subchronic Oral Administration of Gossypol-Acetic Acid (GAA) Alters the Distribution and Utilization of Radioiron in Male Rats

ABSTRACT Gossypol-acetic acid (GAA) has been shown to be a powerful chelator of iron. To determine how subchronic administration of GAA affects the distribution and utilization of radioiron, male Holtzman rats, which had received a daily oral dose of GAA (20 mg/kg body weight) for 16 weeks, were injected i.p. with [59Fe]citrate (activity = 16.5 μCi/kg body weight) and [59Fe] incorporation into circulating erythrocytes, bone marrow, liver, spleen, skeletal muscle, and urine was measured 6, 12, or 24 h after [59Fe] administration. Iron [59Fe] incorporation was enhanced in the spleens, livers, bone marrow, and blood of the GAA-treated rats, and increased as the time post-[59Fe] injection increased. Hematological parameters remained within normal limits throughout the 16-week treatment period, suggesting an erythropoietic compensation in the GAA-treated rats. Iron status was markedly different in the GAA-treated rats at the end of the 16 week treatment period, suggesting altered iron utilization. The data suggest that [59Fe] is preferentially distributed to the erythroid tissues of GAA-treated rats for utilization in erythropoiesis.