The neuroprotective and anti‐apoptotic effects of melatonin on hemolytic hyperbilirubinemia‐induced oxidative brain damage

Abstract

Melatonin exerts protection in several inflammatory and neurodegenerative disorders. To investigate the neuroprotective effects of melatonin in an experimental hemolysis-induced hyperbilirubinemia, newborn Sprague-Dawley rats (25-40 g, n = 72) were injected with phenylhydrazine hydrochloride (PHZ; 75 mg/kg) and the injections were repeated at the 24th hour. Rats were treated with saline or melatonin (10 mg/kg) 30 min before the first and second PHZ injections and 24 h after the 2nd PHZ injections. Control rats (n = 24) were injected with saline, but not PHZ. At sixth hours after the last injections of saline or melatonin, all rats were decapitated. Tumor necrosis factor (TNF)-α, IL-1β, IL-10 and brain-derived neurotrophic factor (BDNF) and S100B levels in the plasma were measured. Brain tissue malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase (MPO) activities were measured, and brain tissues were evaluated for apoptosis by TUNEL method. In the saline-treated PHZ group, hemoglobin, hematocrit levels were reduced, and total/direct bilirubin levels were elevated when compared to control group. Increased plasma TNF-α, IL-1β levels, along with decreased BDNF, S100B and IL-10 values were observed in the saline-treated PHZ group, while these changes were all reversed in the melatonin-treated group. Increased MDA levels and MPO activities in the brain tissues of saline-treated hyperbilirubinemic rats, concomitant with depleted brain GSH stores, were also reversed in the melatonin-treated hyperbilirubinemic rats. Increased TUNEL(+) cells in the hippocampus of saline-treated PHZ group were reduced by melatonin treatment. Melatonin exerts neuroprotective and anti-apoptotic effects on the oxidative neuronal damage of the newborn rats with hemolysis and hyperbilirubinemia.

A review of sleep disorders and melatonin

“…The increase in apoptotic cells in the hippocampus of the PHZ group was ameliorated by melatonin treatment. These studies validate melatonin's role in neuroprotection and antiapoptosis in oxidative-related neuronal injury [41].…”

Melatonin protects against Aβ‐induced neurotoxicity in primary neurons via miR‐132/PTEN/AKT/FOXO3a pathway

“…Accordingly, it has been identified that BDNF/CREB pathway is suppressed in AD brain as well as at the neurons treated with Aβ . Besides, melatonin can attenuate the downregulation of BDNF and protect against neuronal apoptotic during brain damage in rats . Thus, we propose that melatonin might rescue Aβ‐induced neurotoxicity via increasing the level of BDNF and elevating the expression of miR‐132 correspondingly.…”

Dietary Sources and Bioactivities of Melatonin

“…could also reduce the injuries in both gray and white matter and better the neurobehavioral outcomes induced by transient focal cerebral ischemia as a potent radical scavenger [296]. Furthermore, melatonin (10 mg/kg) was found to exhibit the neuroprotective and anti-apoptotic effects on oxidative brain damage induced by hemolytic hyperbilirubinemia in newborn Sprague-Dawley rats by reversing the increased plasma TNF-α, IL-1β levels, as well as the decreased brain derived neurotrophic factor (BDNF), S100 calcium-binding protein B (S100B) and IL-10 values [297]. …”