Hepatotoxicity in Wistar rats following chronic methotrexate administration: a model of human reaction.
The effects of ip administration of methotrexate (MTX) on 3-month-old male Wistar rats were studied. We administered log doses from 125 to 2,000 mug/kg, five times per week for as long as 24 months. The massive doses were promptly lethal, and most rats receiving 500 mug or more/kg died within a few weeks. Severe hematopolietic depression and ulcerative gastrointestinal lesions were observed. Truly chronic intoxication was achieved with the lesser doses. Rats in this category developed serious liver damage, namely, varying degrees of fatty metamorphosis, necrosis, atrophy of hepatic cords, and fibrosis. Hematopoietic depletion occurred in the spleen and bone marrow. Hemosiderosis was prominent in the spleen and liver. Pulmonary lesions--chiefly emphysema, occasionally fibrosis--were found less consistently. These studies demonstrated the ability of MTX to induce lesions, most consistently hepatic, in the Wistar rat, and thus have provided an animal model to evaluate protective measures.
D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D004064:Digestive System / Q000187:drug effects; D005234:Fatty Liver / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000032:analysis / Q000187:drug effects* / Q000473:pathology; D008168:Lung / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D009336:Necrosis; D051381:Rats; D012867:Skin / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects; D014280:Triglycerides / Q000032:analysis
D014280:Triglycerides; D008727:Methotrexate