Department of Medical Biochemistry, Faculty of Medicine, Karabuk University, Karabuk, Turkey.
Department of Histology and Embryology, Faculty of Medicine, Mugla Sıtkı Kocman University, Mugla, Turkey.
J Chem Neuroanat. 2022 Nov;125:102143. doi: 10.1016/j.jchemneu.2022.102143. Epub 2022 Aug 8.
The current study aimed to evaluate the neuroprotective effect of exogenous melatonin against acrylamide (ACR)-induced oxidative stress and inflammatory and apoptotic responses in the brain tissues in pinealectomized rats (PINX). ACR is a toxic chemical carcinogen that occurs owing to the preparation of carbohydrate-rich foods at high temperatures or other thermal processes. The rats who underwent pinealectomy and sham pinealectomy were exposed to ACR (25 mg/kg b.w., orally) alone or with exogenous melatonin (10 mg/kg b.w., i.p.) for 21 consecutive days. Alterations of brain oxidant/antioxidant status, dopamine (DA), Brain-Derived Neurotropic Factor (BDNF) inflammatory mediator and apoptosis during exposure to ACR in pinealectomized rats were more than without pinealectomized rats. Histopathological changes were more in brain tissue of pinealectomized rats after ACR administration. Exogenous melatonin treatment in ACR -exposed rats following pinealectomy increased the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) and improved brain total antioxidant status (TAS) compared to PINX+ACR. Moreover, melatonin suppressed lipid peroxidation, inflammatory pathways and apoptosis in ACR-intoxicated brain tissues. In addition, after exposure to ACR on pinealectomized rats, melatonin treatment ameliorated BDNF and DA levels in brain tissues. Furthermore, exogenous melatonin intervention in ACR-intoxicated rats significantly rescued the architecture of neuronal tissues. In summary, the present study, for the first time, suggested that exogenous melatonin treatment could reduce oxidative damage by increasing the activities of antioxidant enzymes, inhibiting lipid peroxidation and inflammation, and improving histopathological alterations in the brain tissue of pinealectomized rats after ACR administration.
本研究旨在评估外源性褪黑素对去松果体大鼠（PINX）脑组织中丙烯酰胺（ACR）诱导的氧化应激、炎症和凋亡反应的神经保护作用。ACR 是一种有毒的化学致癌物质，由于高温或其他热过程制备富含碳水化合物的食物而产生。接受松果体切除术和假松果体切除术的大鼠单独或与外源性褪黑素（10mg/kg b.w.，腹腔注射）连续 21 天暴露于 ACR（25mg/kg b.w.，口服）。在暴露于 ACR 期间，去松果体大鼠的大脑氧化应激/抗氧化状态、多巴胺（DA）、脑源性神经营养因子（BDNF）炎症介质和细胞凋亡的变化比未去松果体大鼠更为明显。ACR 给药后，去松果体大鼠脑组织的组织病理学变化更为明显。外源性褪黑素治疗可增加抗氧化酶如超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性，改善大脑总抗氧化状态（TAS），与 PINX+ACR 相比。此外，褪黑素抑制 ACR 中毒脑组织中的脂质过氧化、炎症途径和细胞凋亡。此外，在去松果体大鼠暴露于 ACR 后，褪黑素治疗可改善大脑组织中的 BDNF 和 DA 水平。此外，外源性褪黑素干预 ACR 中毒大鼠可显著挽救神经元组织的结构。总之，本研究首次表明，外源性褪黑素治疗可通过增加抗氧化酶活性、抑制脂质过氧化和炎症、改善去松果体大鼠 ACR 给药后大脑组织的组织病理学改变，减轻氧化损伤。
