Antioxidative, membrane protective and antiapoptotic effects of melatonin, in silico study of physico-chemical profile and efficiency of nanoliposome delivery compared to betaine

Abstract

The mechanisms through which melatonin exerts its inhibitory effect on cell death remains insufficiently clarified. The subject of the present study is the evaluation of the hepatoprotective effects of melatonin on the inhibition of apoptotic and oxidative processes and activation of survival pathways, in comparison with betaine, in a primary culture of hepatocytes that have undergone Fas-ligand apoptosis. Melatonin exerted a protective effect on membrane bilayer stability through the inhibition of phosphatidylserine externalization, Bax expression and xanthine oxidase catalyzed free-radical liberation. It also reduced liberation of cellular and membrane-bound enzymes and endonuclease catalyzed DNA fragmentation. Betaine hydrochloride did not exert these effects, when administered alone or co-incubated with anti-Fas antibodies. The in silico Molinspiration tool, which was employed to calculate melatonin and betaine physico-chemical properties and membrane interaction indicated that melatonin may easily cross and interact with biological membranes and maintain membrane phospholipid structural topography. It was documented to occur via non-receptor mechanisms in more than 75%; this may clarify melatonin as suitable for nanoliposome-based delivery, where it was also able to successfully counteract induced oxidative stress. This could not be considered for betaine hydrochloride. The use of lipophilic compounds like melatonin, encapsulated in nanoliposomes, could therefore be a preferable tool in the successful membrane-preservation therapy of liver apoptosis, rather than the use of hydrophilic compounds, like betaine hydrochloride.