Anti-diabetic therapies possess many side effects; thus, searching for alternative strategies with low cost, minimal side effects, and high therapeutic value is very important. The present study aimed to explore the combined use of selenium yeast (SY) and standard anti-diabetic drug pioglitazone (PGZ) for diabetes mellitus (DM) treatment in streptozotocin (STZ)-induced DM. STZ was injected daily intraperitoneally with a low dose (40 mg/kg) into Sprague-Dawley rats to induce DM. The synergistic effect of the SY (0.2 mg/kg) and PGZ (0.65 mg/kg) on DM complications was evaluated after 88 weeks of treatment. The impact of our medication on glucose levels, insulin sensitivity, lipid abnormalities, oxidative mediators, and inflammatory markers was assessed by biochemical techniques. STZ-induced diabetes has toxic effects, including toxic hepatic tissues, lipid disturbances, massive oxidative damage, and hyperinflammation. Experimental rats either treated with monotherapy alone or combined therapy resulted in a significant anti-diabetic effect. The PGZ+ SY combination has the best effect, as illustrated by significant (P < 0.05) decreases in fasting blood glucose, (FBG) insulin, HbA1c, and HOMA-IR levels. This combination attenuated (P < 0.05) lipid disturbances and their associated elevated atherogenicity biomarkers. At the same time, treatments with PGZ+ SY exhibited an anti-inflammatory effect as they ameliorated the increase in inflammatory parameters (CRP, TNF-α, IL-6). Also, it restored the total antioxidant capacity and peroxisome proliferator-activated receptor (PPARƔ) levels that were decreased by STZ-DM induction. In conclusion, this study finds PGZ+ SY as a promising DM therapeutic alternative. This synergistic combination alleviates most DM-related complications and insulin resistance.
Keywords: Anti Antioxidant; Anti Pioglitazone; Anti-diabetic; Anti-inflammatory; Antioxidant; Pioglitazone; Selenium yeast.