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Melatonin Improves Reduced Activities of Membrane ATPases and Preserves Ultrastructure of Gray and White Matter in the Rat Brain Ischemia/Reperfusion Model

Meltem Tuncer1,a*, Bilge Pehlivanoglu1, Selçuk H. Sürücü2, and Turgay Isbir3

1Department of Physiology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey

2Department of Anatomy, Koç University School of Medicine, 34450 Istanbul, Turkey

3Department of Medical Biology, Faculty of Medicine, Yeditepe University, 34755 Istanbul, Turkey

* To whom correspondence should be addressed.

Received November 11, 2020; Revised March 22, 2021; Accepted March 28, 2021
Ischemia/reperfusion (I/R) is among the most frequent neurological problems and early intervention to limit the damage is crucial in decreasing mortality and morbidity. Based on reports regarding beneficial effects of melatonin, we investigated its impact on Na+-K+/Mg2+ ATPase and Ca2+/Mg2+ ATPase activities and ultrastructure of gray and white matter in the rat forebrain I/R model. Adult Wistar-albino rats (n = 78), were randomized into control, ischemia (I), ischemia/reperfusion (I/R), low (I/R + melatonin 400 µg/kg), moderate (I/R + melatonin 1200 µg/kg), and high (I/R + melatonin 2400 µg/kg) dose melatonin. Two-vessel occlusion combined with hypotension (15 min) induced ischemia and reperfusion (75 min) achieved by blood reinfusion were performed. Activities of the membrane-bound enzyme, brain malondialdehyde levels, and brain matter ultrastructure were examined in frontoparietal cortices. Melatonin lowered production of malondialdehyde in a dose-dependently. The enzyme activities attenuated under I and I/R, improved with melatonin treatment. I and I/R severely disturbed gray and white matter morphology. Melatonin, in all applied doses, decreased ultrastructural damages in both gray and white matter. Favorable effects of melatonin can be attributed to its antioxidant properties suggesting that it could be a promising neuroprotective agent against I/R injury being effective both for gray and white matter due to favorable biological properties.
KEY WORDS: malondialdehyde, melatonin, Na+-K+/Mg2+ ATPase, Ca2+/Mg2+ ATPase, reperfusion injury

DOI: 10.1134/S0006297921050035