Effect of alphaxalone-alphadolone on some enzymatic activities from rat brain

The changes induced by alphaxalone-alphadolone (3:1) in the cerebral enzymatic activities of the Krebs' cycle (citrate synthase, malate dehydrogenase) and electron transfer chain (total NADH-cytochrome c reductase and cytochrome oxidase) were studied. In addition, the activation of lactate dehydrogenase (for the glycolytic pathway) and of acetylcholine esterase (as indicative of transmission) were investigated. These enzymatic activities were evaluated in the homogenate in toto and/or in the crude mitochondrial fraction of rat brain, since these enzymes are variously located in the cytoplasm. Two relationships were studied: a) dose/action (0.5, 1. 2, 4, 8, 16 and 32 mg . kg-1) by measurements carried out 60 min after i.p. administration; b) time/action (16 mg . kg-1 i.p.; measurements 15, 30, 60, 120 and 240 min after administration). The results show that in both kinds of trials alphaxalone-adphadolone reduced only the activity of the enzyme cytochrome oxidase evaluated on the brain homogenate in toto. More specifically, with regard to the dose/action relationship, the effect occurred starting with the dose of 2 mg . kg-1 and did not take place linearly with the higher ones. As to the time/action relationship, the effect began 60 min after administration, the changes being observed also at the subsequent times. The data obtained are discussed with regard to the interactions between alphaxalone-alphadolone and mitochondrial enzymatic systems, and compared with the effects of phenobarbital on the same systems