Hepatotoxicity in Wistar rats following chronic methotrexate administration: action

ABSTRACT-The effects of ip administration of methotrexate (MTX) on 3-month-old male Wistar rats were studied. We adminis-tered log doses from 125 to 2,000 ltg/kg, five times per week for as long as 24 months. The massive doses were promptly lethal, and most rats receiving 500 Itg or more/kg died within a few weeks. Severe hematopoietic depression and ulcerative gas-trointestinal lesions were observed. Truly chronic intoxication was achieved with the lesser doses. Rats in this category devel-oped serious liver damage, namely, varying degrees of fatty metamorphosis, necrosis, atrophy of hepatic cords, and fibrosis. Hematopoietic depletion occurred in the spleen and bone mar-row. Hemosiderosis was prominent in the spleen and liver. Pul-monary lesions-chiefly emphysema, occasionally fibrosis-were found less consistently. These studies demonstrated the ability of MTX to induce lesions, most consistently hepatic, in th