Pinoline and melatonin protect against H₂O₂-induced lipid peroxidation in rat brain homogenates

The brain is particularly susceptible to free radical damage, and it is therefore important to find agents that protect against this process. The chief secretory product of the pineal gland, melatonin, is a well known antioxidant. Pinoline is a recently discovered compound with structural similarity to melatonin. In the search for a new neuroprotective agent, the antioxidant capacity of pinoline is compared to that of melatonin. Lipid peroxidation was induced by adding H₂O₂ to rat brain homogenates. The degree of lipid peroxidation was assessed by estimating the levels of thiobarbituric acid reactive substances, malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA). The antioxidant capacity of pinoline and melatonin was measured as percent inhibition of lipid peroxidation in rat brain homogenates after the addition of H₂O₂. Both pinoline and melatonin were found to inhibit lipid peroxidation in a dose-dependent manner. Under these in vitro conditions, pinoline was found to be 7 times more effective than melatonin in reducing MDA + 4-HDA levels, with an IC₅₀ = 0.1 mM for pinoline and an IC₅₀ = 0.7 mM for melatonin.