Role of pinoline and melatonin in stabilizing hepatic microsomal membranesagainst oxidative stress

We investigated the influence of pinoline (0.01-1.5 mM) on microsomal membr ane fluidity before and after rigidity was induced by oxidative stress. In addition, we tested the effect of pinoline in the presence of 1 mM melatoni n. The fluidity in rat hepatic microsomes was monitored using fluorescence spectroscopy and it was compared to the inhibition of malonaldehyde (MDA) p lus 4-hydroxyalkenals (4-HDA) production as a reflection of lipid peroxidat ion. Below 0.6 mM, pinoline inhibited membrane rigidity in a manner paralle l to its inhibitory effect on MDA + 4-HDA formation. At concentrations betw een 1-1.5 mM, pinoline was less effective in stabilizing microsomal membran es than was predicted from its inhibition of lipid peroxidation. The additi on of 1 mM melatonin enhanced the membrane-stabilizing activity of pinoline (0.01-0.6 mM). This cooperative effect was not observed for concentrations of pinoline between 1-1.5 mM. When pinoline was tested without induced oxi dative damage, 1-1.5 mM pinoline maintained membrane fluidity at the same l evel as that recorded after induced lipid peroxidation. The results suggest that pinoline may be another pineal molecule that prevents membrane rigidi ty mediated by lipid peroxidation and this ability is enhanced by melatonin .