Obrosov Alexander, Shevalye Hanna, Coppey Lawrence J, Yorek Mark A
a Department of Internal Medicine , University of Iowa , Iowa City , IA , USA.
b Department of Veterans Affairs Iowa City Health Care System , Iowa City , IA , USA.
Free Radic Res. 2017 Apr;51(4):360-367. doi: 10.1080/10715762.2017.1315767. Epub 2017 Apr 19.
In this study, we sought to determine the efficacy of tempol on multiple neuropathic endpoints in a diet-induced obese mouse, a model of pre-diabetes, and a high-fat fed low-dose streptozotocin treated mouse, a model of type 2 diabetes. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperdine -1-oxyl) is a low molecular weight, water soluble, membrane permeable, and metal-independent superoxide dismutase mimetic that has been widely used in cellular studies for the removal of intracellular and extracellular superoxide. This in vivo study was designed to be an early intervention. Fourteen weeks post-high-fat diet (6 weeks post-hyperglycemia) control, obese, and diabetic mice were divided into no treatment and treatment groups. The treated mice received tempol by gavage (150 mg/kg in water), while the untreated mice received vehicle. The diet-induced obese and the diabetic mice were maintained on the high-fat diet for the duration of the study, while the control group was maintained on the standard diet. Obesity and diabetes caused slowing of motor and sensory nerve conduction, reduction in intraepidermal nerve fiber density, thermal hypoalgesia, and mechanical allodynia. Treatment with tempol partially or completely protected obese and diabetic mice from these deficits. These studies suggest that tempol or other effective scavengers of reactive oxygen species may be a viable option for treating neural complications associated with obesity or type 2 diabetes.
在本研究中，我们试图确定Tempol对饮食诱导肥胖小鼠（一种糖尿病前期模型）以及高脂喂养低剂量链脲佐菌素处理小鼠（一种2型糖尿病模型）多个神经病变终点的疗效。Tempol（4-羟基-2,2,6,6-四甲基哌啶-1-氧基）是一种低分子量、水溶性、可透过细胞膜且不依赖金属的超氧化物歧化酶模拟物，已广泛用于细胞研究中以清除细胞内和细胞外超氧化物。这项体内研究设计为早期干预。高脂饮食14周后（高血糖6周后），将对照、肥胖和糖尿病小鼠分为未治疗组和治疗组。治疗组小鼠通过灌胃给予Tempol（溶于水中，剂量为150 mg/kg），而未治疗组小鼠给予赋形剂。在研究期间，饮食诱导肥胖和糖尿病小鼠维持高脂饮食，而对照组维持标准饮食。肥胖和糖尿病导致运动和感觉神经传导减慢、表皮内神经纤维密度降低、热痛觉减退和机械性异常性疼痛。Tempol治疗可部分或完全保护肥胖和糖尿病小鼠免受这些缺陷的影响。这些研究表明，Tempol或其他有效的活性氧清除剂可能是治疗与肥胖或2型糖尿病相关神经并发症的可行选择。
