Hepatic Collagen Production in the Rat Is Unaffected by Methotrexate

Abstract

Methotrexate (MTX) has been implicated in the pathogenesis of hepatic fibrosis. However, no information exists regarding the effects of MTX on hepatic collagen metabolism. Therefore, we studied the role of MTX in hepatic collagen production in vivo in rats receiving an 8-week course of varying doses of MTX. Twenty-four hours prior to sacrifice animals received an injection of [5-3H]proline. Collagen was extracted with hot trichloroacetic acid and the proteinbound [3H]hydroxyproline was used as a measure of de novo collagen production. The hepatic collagen content was essentially the same in the control and treatment groups in spite of evidence of hepatotoxicity. Similarly, no significant differences were present among the control and MTXtreated groups in the de novo absolute collagen production. In summary, we found no evidence of increased hepatic fibrogenesis in small groups of animals after 8 weeks of treatment with MTX. Data clearly supporting the claim that MTX itself is responsible for hepatic fibrosis are lacking.