THE EFFECT OF NORDIHYDROGUAIARETIC ACID, AN INHIBITOR OF PROSTAGLANDIN AND LEUKOTRIENE BIOSYNTHESIS, ON HEMATOPOIESIS OF GAMMA-IRRADIATED MICE

The effects of the inhibition of the cyclooxygenase and lipoxygenase m etabolic pathways of arachidonic acid on the postirradiation recovery of hematopoietic functions in mice were investigated. Nordihydroguaiar etic acid (NDGA), an inhibitor of prostaglandin (PG) and leukotriene ( LT) production, was given to animals in single doses (0.015 to 0.75 mg /mouse) 1 hour before 5 Gy of total-body gamma-irradiation. Enhanced h ematopoietic recovery in terms of exogenous and endogenous spleen colo nies, femoral granulocyte-macrophage colony-forming cells and peripher al blood granulocyte levels was observed at higher doses of NDGA. The treatment used influenced neither lymphocyte nor erythrocyte postirrad iational levels or hemoglobin concentration. A comparison of the effec ts induced by a high dose of NDGA (0.3 mg per mouse) with those observ ed after an isomolar dose of indomethacin (an inhibitor of PG producti on) indicated only slight differences between these two drugs. An isom olar dose of esculetin (an inhibitor of LT production) had no effect o n the postirradiation behavior of hematopoiesis. The results suggest t hat the inhibition of PG production plays the main role in the mechani sm of NDGA action. Inhibition of LT production seems to be of less imp ortance for hematopoiesis in these in vivo conditions.