Vincristine is a cytotoxic tubulin binding agent, derived from the periwinkle plant, Vinca rosea Linn. It has been known as a potent mitotic inhibitor that has found their place as effective drug in combination chemotherapy regimens for the treatment of human leukemias, lymphomas and a variety of solid tumors.
The major antitumor effect of this agent apears to be related to its high affinity binding to the basic protein subunit of microtubules, tubulin, which results in disrup-tion of the mitotic spindle apparatus and arrest cells in metaphase. Neurotoxicity is dose-limiting toxicity of administration of vincristine. Vincristine also acts on normally proliferating cells.
The author has investigated the effect of vincristine on the mouse liver histochemial-ly observing the change in the activities of alkaline phosphatase and adenosine triphosphatase (ATPase).
The mice of the vincristine treated group were given 2.5 mg per kg of body weight of mouse in the form of vincristine in 0.9 % sodium chloride and the animals of con-trol group were given 0.9% sodium chloride only through intraperitoneal injection. After administration, the animals were killed at intervals of 6, 12, 24 and 36 hours. The specimens which were obtained from the anterior lobe of the liver, were fixed in 10%-neutral formalin -at 4°C and sectioned at 16μm thickness in a frozen cryostat. The activities of alkaline phosphatase and ATPase were observed by Gomori´s method and by Wachstein-Meisel´s method, respectively.
The results are as follows:
1. The activity of alkaline phosphatase was weakly positive in the perioportal and intermedicate zones, trace positive in the central zone of the hepatic lobule of the 6 hours vincristine treated group. Trace positive reaction was observed in the hepatic lobule of 12 hours vincristine treated group. Negative reaction in the cen-tral zone, trace positive reaction in the intermediate zone and weakly postive reac-tion in the periportal zone were observed. Trace positive reaction was observed in the central zone ane weakly positive reaction was seen in the intermediate and periportal zone of the hepatic was seen in the intermediate and periportal zone of the hepatic lobule of 36 hours vincristine treated group.
2. ATPase activity was weakly positive in the central and periportal zones and trace positive in the intermediate zone of the hepatic lobule of 6 hours vincristine treated group. Trace positive reaction was observed in the entire hepatic lobule of 12 hours vincristine treated group. There are weakly posotive in the 24 hours vincristine treated group and mdoerately positive reaction in the whole hepatic lobule of the 36 hours vincristine treated group.
Consequently, it is suggested that vincristine decreases activities of alkaline phosphatase and ATPase in the liver, due probably to the cytotoxic effect of the drug on the liver.
|