Protective effect of hydrogen on diabetic peripheral neuropathy by suppressing nulcear factor-kappaB pathway

Abstract

Objective To investigate the effect of hydrogen on streptozotocin (STZ)-induced diabetic rat models with peripheral neuropathy and explore the possible mechanism. Methods Eighteen male Sprague⁃Dawley (SD) rats were randomly divided into model group (N = 6), hydrogen-treated group (N = 6) and normal control group (N = 6). After fasting for 12 h, experimental diabetic rat models were established by intraperitoneal injection of STZ (65 mg/kg of single dose), while normal control group only received a same dose of citrate buffer. Diabetes was confirmed with a fasting plasma glucose more than 16.67 mmol/L 48 h after STZ injection. After diabetic models were established successively, hydrogen-rich saline (5 ml/kg) was administered by intraperitoneal injection in hydrogen-treated group daily in 7th and 8th week after diabetes induction. Corresponding model and normal control groups received a same dose of normal saline. Changes of sciatic function and pain behavior in rats of different groups were measured to investigate the effect of hydrogen-rich saline. Proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and nuclear factor-kappaB (NF-κB) p65 expression were then determined to clarify the possible mechanism of hydrogen-mediated protection. Results 1) Compared with normal control group, body weight in model group decreased significantly, while plasma glucose levels increased significantly (P = 0.000, for all) 8 weeks after STZ induction. Hydrogen did not show any effects on body weight and plasma glucose levels of treated rat models in comparison with model group (P = 0.256, 0.821). 2) Compared with normal control group, motor nerve conduction velocity (MNCV), heat pain threshold (HPT) and mechanical withdrawal threshold (MWT) decreased significantly in model group (P = 0.000, for all), but increased significantly in hydrogen-treated group when compared with model group in the 8th week (P = 0.000, for all). 3) Hydrogen also reduced the positively expressed cells of NF-κB p65 (P = 0.000) as well as levels of TNF-α and IL-6 (P = 0.000, for all). Conclusion Inflammation may participate and exaggerate painful diabetic neuropathy. Besides, hydrogen has the protective potential of ameliorating neuroinflammation and peripheral nerve injury by suppressing NF-κB pathway and its downstream inflammatory cytokines.