Methotrexate (MTX), a folic acid analog, so effectively inhibits the synthesis of thymidine nucleotide that the synthesis of DNA is subsequently interrupted. It is widely used as an anticancer drug for the thearpy of psoriasis and acute lymphatic leukemia. It inhibits not only DNA synthesis but also the protein synthesis and glycolysis, and general and cytotoxic toxicity are, therefore, observed during the therapy. Therefore the author undertook the present study to pursue the effect of methotrexate on the alkaline phosphatase and acid phosphatases in the liver.
Albino mice, ICR strain, weighing 20g were used as experimental animals. The experimental: animals were killed at 12, 24, 48, 72 and 96 hours after administration of 14 mg/kg of methotrexate. The specimens obtained from the liver were fixed and sectioned with 16 μm thickness -in a frozen cryostat. The activities of alkaline phosphatase and acid phosphatase were. observed by the Gomori´s method for histochemical study.
The results obtained were as follows.
1. The activity of alkaline phosphatase was negative in the intermediate zone and trace positive in the periportal zone of the hepatic lobule in the 12 hours-MTX treated group. The activity of alkaline phosphatase was restored toward normal with time, moderate positive activity being in the intermediate zone and strong positive activity being in the peroportal zone of the 96 hours-MTX treated group.
2. The activities of acid phosphatase were increased with time, a moderate positive activity being in the central zone of the hepatic lobule of the 24 hour-MTX treated group and a strong positive activity being in the central zone of the hepatic lobule of the 48 hour-MTX treated group. A Moderate positive activity was observed in the central zone of the hepatic lobule of the 72 hour and 96 hour-MTX treated group.
Consequently, it is suggested that methotrexate decreases alkaline phosphatase activity and increases the acid phosphatase activity in the liver due to its cytotoxic effects.
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