Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania.
Medicina (Kaunas). 2023 Jul 27;59(8):1375. doi: 10.3390/medicina59081375.
: Worldwide, approximately 500 million people suffer from diabetes and at least 50% of these people develop neuropathy. Currently, therapeutic strategies for reducing diabetic neuropathy (DN)-associated pain are limited and have several side effects. The purpose of the study was to evaluate the antihyperalgesic action of different sildenafil (phosphodiesterase-5 inhibitor) and metformin (antihyperglycemic agent) combinations in alloxan-induced DN. : The study included 100 diabetic mice and 20 non-diabetic mice that were subjected to hot and cold stimulus tests. Furthermore, we determined the influence of this combination on TNF-α, IL-6 and nitrites levels in brain and liver tissues. : In both the hot-plate and tail withdrawal test, all sildenafil-metformin combinations administered in our study showed a significant increase in pain reaction latencies when compared to the diabetic control group. Furthermore, all combinations decreased blood glucose levels due to the hypoglycemic effect of metformin. Additionally, changes in nitrite levels and pro-inflammatory cytokines (TNF-α and IL-6) were observed after 14 days of treatment with different sildenafil-metformin combinations. : The combination of these two substances increased the pain reaction latency of diabetic animals in a dose-dependent manner. Moreover, all sildenafil-metformin combinations significantly reduced the concentration of nitrites in the brain and liver, which are final products formed under the action of iNOS.
: 在全球范围内，约有 5 亿人患有糖尿病，其中至少有 50%的人患有神经病变。目前，减轻糖尿病神经病变（DN）相关疼痛的治疗策略有限，且具有多种副作用。本研究的目的是评估不同西地那非（磷酸二酯酶-5 抑制剂）和二甲双胍（抗高血糖药物）组合对链脲佐菌素诱导的 DN 的抗痛觉过敏作用。: 该研究纳入了 100 只糖尿病小鼠和 20 只非糖尿病小鼠，对其进行了冷热刺激测试。此外，我们还测定了这种组合对大脑和肝脏组织中 TNF-α、IL-6 和亚硝酸盐水平的影响。: 在热板和尾部退缩试验中，与糖尿病对照组相比，本研究中给予的所有西地那非-二甲双胍组合均显著延长了疼痛反应潜伏期。此外，由于二甲双胍的降血糖作用，所有组合均降低了血糖水平。此外，在给予不同西地那非-二甲双胍组合治疗 14 天后，观察到亚硝酸盐水平和促炎细胞因子（TNF-α和 IL-6）的变化。: 这两种物质的组合以剂量依赖的方式增加了糖尿病动物的疼痛反应潜伏期。此外，所有西地那非-二甲双胍组合均显著降低了大脑和肝脏中亚硝酸盐的浓度，这是在 iNOS 作用下形成的终产物。
