Effect of melatonin and nifedipine on some antioxidant enzymes and different energy fuels in the blood and brain of global ischemic rats.

Abstract

The brain normally derives most of its energy from the aerobic oxidation of glucose and therefore it must be nourished with a rich supply of both glucose and oxygen. Interference with the blood supply, such as in ischemia, could shift the brain to search for another source of energy and to spare its own glucose. Ischemia results not only in energy fuel disturbance, but also in free radical formation and Ca(2+) homeostasis disruption. Therefore, our investigations studied the influence of ischemia on energy fuels, on some natural free radical scavengers, and the relationship between the changes of these parameters in brain and blood. Each of these was also studied under the influence of melatonin, a well-known free radical scavenger, and nifedipine, a Ca(2+)-channel blocker and antioxidant, during ischemia followed by reperfusion (I/R). Adult male Wistar rats were subjected to global ischemia by occlusion of the two carotid arteries for 1 hr (group I), followed by reperfusion for another hour in group II. Drugs were injected after ischemia (group I), and before or after reperfusion onset in the second group. Two series of animals were used. In the first series the effect of the two drugs on the activity of superoxide dismutase (SOD), glutathione reductase (GR), and lactate dehydrogenase (LDH) was investigated in the cytosolic fraction of four brain areas, viz., cortex (CC), thalamus/hypothalamus (T/TH), midbrain (MB) and medulla, pons and cerebellum (MPC). Moreover, the level of both SOD and GR in the erythocytes of these rats was also estimated. In the second series, we studied the effect of each drug on the content of glucose and beta-hydroxybutyrate (beta-HB) in whole brain, in addition to the plasma levels of glucose, beta-HB and lactate. The results showed that (i), ischemia elevated the brain levels of LDH and beta-HB, as well as the plasma level of glucose, beta-HB, lactate and erythocytic GR. Conversely, it lowered glucose, SOD and GR levels in the brain; (ii), reperfusion reversed the ischemic effect on all the previously altered parameters except for plasma levels of lactate and glucose; (iii), melatonin (10 mg/kg, i.p) and nifedipine (1.5 mg/kg, i.p), restored the energy fuel levels in the brain of ischemic and I/R rats, as well as the ischemic effect on the erythocyte activities of SOD and GR. Furthermore, both drugs reversed I/R effect on the cytosolic activities of the antioxidant enzymes. We conclude that melatonin and nifedipine are both neuroprotective with improvement in the antioxidant system and energy fuels.