Abstract
Summary
Mice were subjected to prolonged high dose treatment with methyldopate hydrochloride (Aldomet), and evaluated for the development of positive direct antiglobulin reactions and anemia. NZB and A/J strains which are genetically susceptible to autoimmune disease and the nonsusceptible CBA/H-T6 strain were studied. Methyldopate was administered orally or subcutaneously at doses of 4-200 mg/kg body weight beginning at 2-3 months of age. Treatment by injection was carried out for 3.4-10.7 months while oral treatment was continued for the life of the animal. The time of onset and severity of the spontaneous autoimmune hemolytic anemia in NZB mice were not influenced by methyldopate treatment. Microhematocrit levels decreased significantly with advancing age in A/J and CBA mice, and positive direct erythrocyte antiglobulin reactions were noted in A/J mice at 21 months of age. These conditions occurred equally in experimental and control groups, however, and could not be attributed to methyldopate treatment. It is concluded that age and a genetic predisposition to autoimmune disorders are not sufficient to induce methyldopa associated autoimmune hemolytic anemia in mice even with long term high dose drug treatment.
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