Methotrexate (MTX) effect on pancreatic enzymes in leukemic mice

Abstract

We evaluated the effects of MTX on normal and leukemic mice (L-1210) in order to determine the effects of MTX on the pancreas in both leukemic and normal control mice. The mice were divided into two experiments according to their treatment schedule. The first group consisted of mice with L-1210 leukemia and normal controls treated with escalating doses of MTX or with placebo at 10, 15, 20, 25, 30, or 45 mg/kg. These mice were all arbitrarily sacrificed at 48 hr. The second group consisted of mice with L-1210 leukemia and normal controls treated with an arbitrary dose of MTX (20 mg/kg) or with placebo and sacrificed at spaced time intervals of 12, 24, 48, and 96 hr after MTX administration. Both L-1210 and normal nonleukemic mice were examined for histological changes in the pancreas as well as pancreatic zymogen enzyme levels. In general, the maximal effect on the pancreas occurred at a dose of 20 mg/kg of MTX and at 48 hr following MTX administration. Histologically, in the L-1210 leukemic mice, there was leukemic infiltration, diminished acini, and fatty changes in the pancreas; these findings were less pronounced following treatment with MTX compared to those treated with placebo. All pancreatic enzymes in untreated leukemic mice were significantly diminished (P<0.001) compared to normal mice. Amylase and lipase were decreased more than trypsin and chymotrypsin. The zymogen enzymes in MTX-treated normal mice responded in a hyperbolar fashion, falling to a nadir at 20 mg/kg of MTX. In contrast, in the MTX-treated leukemic mice, the zymogen enzymes increased significantly reaching a peak at 20 mg/kg of MTX and then falling off with increasing MTX doses.