Dag Yusuf, Yildirim Serkan, Sengul Emin, Aykurt Furkan, Gok Melahat, Cinar Ali
Department of Physiology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey.
Department of Pathology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey.
BMC Pharmacol Toxicol. 2025 Mar 11;26(1):57. doi: 10.1186/s40360-025-00900-8.
This study examined the antioxidant, anti-inflammatory, and neuroprotective effects of melatonin (MEL) against acrylamide (ACR)-induced neurotoxicity in Sprague-Dawley rats. The experimental groups included control, ACR, MEL10+ACR, MEL20+ACR, and MEL20. MEL at doses of 10 and 20 mg/kg, and ACR at 50 mg/kg, were administered intraperitoneally for 14 days. On the 15th day, locomotor activity was assessed, and brain tissues were analyzed biochemically, molecularly, and histopathologically. ACR exposure decreased locomotor activity, increased malondialdehyde (MDA) and reduced glutathione (GSH) levels, indicating oxidative stress, and decreased antioxidant enzyme activities (SOD, GPx, CAT). High-dose MEL (MEL20+ACR) effectively reduced lipid peroxidation and restored antioxidant enzyme activities. MEL treatment also suppressed proinflammatory cytokines (TNF-α, IL-1β, IL-6) and neuronal nitric oxide synthase (nNOS), demonstrating anti-inflammatory effects. Furthermore, MEL mitigated ACR-induced neurotoxicity by reducing acetylcholinesterase (AChE) and monoamine oxidase (MAO) levels. ER stress markers (GRP78, ATF4, ATF6, sXBP1, CHOP) and apoptotic markers (Bax, Caspase-3) were elevated following ACR exposure but were suppressed by MEL. Additionally, MEL reduced ACR-induced increases in 8-hydroxy-2-deoxyguanosine (8-OHdG) and glial fibrillary acidic protein (GFAP), markers of DNA damage and astrocyte activation, respectively. These findings underscore the potential of MEL to counteract ACR-induced neurotoxicity through its comprehensive antioxidant, anti-inflammatory, and neuroprotective actions.
本研究考察了褪黑素（MEL）对丙烯酰胺（ACR）诱导的Sprague-Dawley大鼠神经毒性的抗氧化、抗炎和神经保护作用。实验组包括对照组、ACR组、MEL10+ACR组、MEL20+ACR组和MEL20组。分别以10和20mg/kg的剂量腹腔注射MEL，以50mg/kg的剂量腹腔注射ACR，持续14天。在第15天，评估运动活性，并对脑组织进行生化、分子和组织病理学分析。ACR暴露降低了运动活性，增加了丙二醛（MDA）水平，降低了谷胱甘肽（GSH）水平，表明存在氧化应激，并降低了抗氧化酶活性（超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶）。高剂量MEL（MEL20+ACR）有效降低了脂质过氧化，并恢复了抗氧化酶活性。MEL治疗还抑制了促炎细胞因子（肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6）和神经元型一氧化氮合酶（nNOS），显示出抗炎作用。此外，MEL通过降低乙酰胆碱酯酶（AChE）和单胺氧化酶（MAO）水平减轻了ACR诱导的神经毒性。ACR暴露后，内质网应激标志物（葡萄糖调节蛋白78、活化转录因子4、活化转录因子6、剪接型X盒结合蛋白1、C/EBP同源蛋白）和凋亡标志物（Bax、半胱天冬酶-3）升高，但被MEL抑制。此外，MEL降低了ACR诱导的8-羟基-2'-脱氧鸟苷（8-OHdG）和胶质纤维酸性蛋白（GFAP）的增加，8-OHdG和GFAP分别是DNA损伤和星形胶质细胞活化的标志物。这些发现强调了MEL通过其全面的抗氧化、抗炎和神经保护作用来对抗ACR诱导的神经毒性的潜力。
