Pharmacological aspects of N-acetyl-5-methoxytryptamine (melatonin) and 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (pinoline) as antioxidants: Reduction of oxidative damage in brain region homogenates

Oxygen consumption is a necessity for all aerobic organisms, but oxygen is also a toxic molecule that leads to the generation of free radicals. The br ain consumes a high Percentage of the oxygen inhaled (18.5%), and it contai ns large amounts of unsaturated fatty acids, which makes it highly suscepti ble to lipid peroxidation. Melatonin (N-acetyl-5-methoxytryptamine), the ma in secretory product of the pineal gland, is a free radical scavenger that was found to protect against lipid peroxidation in many experimental models . Another compound found in the pineal gland is pinoline (6-methoxy-1,2,3,4 -tetrahydro-beta-carboline). Pinoline is structurally related to melatonin. Evidence suggests that pinoline may have an antioxidant capacity similar t o that of melatonin. In this study, the ability of pinoline to protect agai nst H2O2-induced lipid peroxidation of different rat brain homogenates (fro ntal cortex, striatum, cerebellum, hippocampus, and hypothalamus) was inves tigated. The degree of lipid peroxidation was assessed by estimating the le vels of thiobarbituric acid reactive substances, malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA). Pinoline's antioxidant capacity was compared wit h that of melatonin. Both melatonin and pinoline reduced the level of MDA a nd 4-HDA in a dose-dependent manner in all brain regions tested. To compare the antioxidant capacities, percent-inhibition curves were created, and th e IC50 values were calculated. The IC50 values for melatonin were higher in all brain regions than were those for pinoline. The IC50 values for melato nin in the five different brain regions ranged from 0.16mM-0.66 mM, and for pinoline, they ranged from 0.04 mM-0.13 mM. The possibility of synergistic interactions between melatonin and pinoline were also determined using the method of Berenbaum. Little evidence for either synergistic, additive, or antagonistic interactions between melatonin and pinoline was found.