Mitigative effect of sodium alginate on streptozotocin (STZ)-induced diabetic neuropathy through regulation of redox status and miR-146a in the rat sciatic nerve

Diabetic peripheral neuropathy (DPN) is a significant complication of diabetes with limited effective therapeutic options. Sodium alginate (SA), a natural polysaccharide from brown algae, has demonstrated health benefits, however, whether it can treat streptozotocin (STZ)-induced DPN remains unclear. The present experiment aimed to test the preventive role of SA on STZ-induced DPN in rats and explored the possible mechanisms. The DPN rat model was established in rats by intraperitoneal injection of a single dose of 40 mg/kg b.w. STZ, and SA (200 mg/kg b.w./day) was orally administered for 28 days after type 2 diabetes mellitus (T2DM) induction. The obtained findings revealed that STZ significantly increased serum levels of FBG, HOMA-IR, TC, TG, VLDL-C, and LDL-C, while decreased serum insulin, incretin GLP-1, HDL-C, and lipase activity. In the sciatic nerves, STZ significantly increased proinflammatory cytokine levels (IL-1β, IL-6, and TNF-α), caspase-3 (a pro-apoptotic protein), markers of oxidative stress (MDA and NO), and AGEs. In parallel, STZ induced a significant decline in the activities of enzymatic antioxidants, <i>viz.</i>, SOD, CAT, and GPx, and non-enzymatic GSH. These changes were accompanied by a low expression of miR-146a in the sciatic nerves of DPN rats. Except for HOMA-IR, SA treatment to STZ injected rats significantly improved these parameters and helped to rescue the neurological morphology of the sciatic nerve fibers. In conclusion, SA mitigated experimental DPN, and this might be due to its ability to suppress hyperglycemic-hyperlipidemic effects, counteract the overactivation of inflammatory molecules, increase miR-146a expression, modulate oxidative dysregulation, and reduce cell apoptosis.