Magadmi Rania M, Alsulaimani Mujahid A, Al-Rafiah Aziza R, Ahmad Muhammad Saeed, Esmat Ahmed
Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Neuroscience Unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Front Pharmacol. 2021 Apr 13;12:613634. doi: 10.3389/fphar.2021.613634. eCollection 2021.
Diabetic neuropathy (DN) commonly occurs in diabetics, affecting approximately 50% of both type 1 and 2 diabetic patients. It is a leading cause of non-traumatic amputations. Oxidative stress could play a key role in the pathophysiology of DN. This study aimed to investigate the potential neuroprotective effect of carvedilol on STZ-induced DN in rats. Thirty male Sprague Dawley rats (weighing 200-250 g) were randomly divided into five groups (six/group), where group 1 (negative control) received only the vehicle (0.5% of carboxymethyl cellulose orally 1 ml/kg). DN was induced by a single injection of remaining rats with streptozotocin (STZ; 50 mg/kg, i.p.). After diabetes induction, group 2 served as the diabetic untreated animals; while groups 3 and 4 were treated with carvedilol (1 and 10 mg/kg/d, orally, respectively). Group 5 received -lipoic acid as a reference neuroprotective (100 mg/kg/d, orally). All treatments were continued for 45 days after diabetes induction, followed by behavioural tests. After sacrificing the animals, dorsal root ganglia, and sciatic nerves were collected for histopathological examination and biochemical assessments. Briefly, STZ administration caused cold allodynia, induced oxidative stress, and increased nerve growth factor (NGF) concentration. Nevertheless, carvedilol improved the behavioural tests, ameliorated the oxidative imbalance as manifested by reducing malondialdehyde, restoring glutathione content, and superoxide dismutase activity. Carvedilol also decreased NGF concentration in DRG homogenate. In conclusion, this study demonstrates the neuroprotective effect of carvedilol in an experimentally induced DN rat model through-at least partly-its antioxidant effect and reduced NGF concentration in DRG.
糖尿病神经病变（DN）常见于糖尿病患者中，1型和2型糖尿病患者中约有50%会受到影响。它是导致非创伤性截肢的主要原因。氧化应激可能在DN的病理生理过程中起关键作用。本研究旨在探讨卡维地洛对链脲佐菌素（STZ）诱导的大鼠糖尿病神经病变的潜在神经保护作用。将30只雄性Sprague Dawley大鼠（体重200 - 250克）随机分为五组（每组6只），其中第1组（阴性对照组）仅接受赋形剂（0.5%羧甲基纤维素，口服1毫升/千克）。其余大鼠单次腹腔注射链脲佐菌素（STZ；50毫克/千克）诱导糖尿病神经病变。糖尿病诱导后，第2组作为未治疗的糖尿病动物；而第3组和第4组分别用卡维地洛（1和10毫克/千克/天，口服）治疗。第5组接受α -硫辛酸作为参考神经保护剂（100毫克/千克/天，口服）。糖尿病诱导后所有治疗持续45天，随后进行行为测试。处死动物后，收集背根神经节和坐骨神经进行组织病理学检查和生化评估。简而言之，给予STZ导致冷痛觉过敏，诱导氧化应激，并增加神经生长因子（NGF）浓度。然而，卡维地洛改善了行为测试结果，减轻了氧化失衡，表现为丙二醛减少、谷胱甘肽含量恢复和超氧化物歧化酶活性恢复。卡维地洛还降低了背根神经节匀浆中NGF的浓度。总之，本研究表明卡维地洛在实验诱导的糖尿病神经病变大鼠模型中具有神经保护作用，至少部分是通过其抗氧化作用以及降低背根神经节中NGF的浓度实现的。
