Rutin and selenium nanoparticles protected against STZ-induced diabetic nephropathy in rats through downregulating Jak-2/Stat3 pathway and upregulating Nrf-2/HO-1 pathway

Diabetic nephropathy (DN) is a renal complication of diabetic hyperglycemia. The Signal transducer and acti-vator of transcription 3 (Stat3) is a center molecule of the chronic inflammation causing DN progression. Therefore, the study investigated the possible inhibitory effects of Rutin (Ru) and Selenium (Se), formulated as nanoparticles (SeNPs), on Stat3 pathway in streptozotocin (STZ)-induced DN in Sprague-Dawley rats. Ru (100 mg/kg/orally) and SeNPs (equivalent to 5 mg of Se/kg/orally) were given as treatment for eight weeks. An assessment of fasting blood glucose, renal function biomarkers, GSH, and MDA was carried out spectrophoto-metrically. ELISA assessment of renal IL-6, NF-KB, TNF-alpha, Jak-2, and p-Stat3 was performed. Sirt-1, Nrf-2, and HO-1 were assessed immunohistochemically. DN group receiving Ru + SeNPs showed a decrease in fasting blood glucose, serum creatinine, and urea (163.8 +/- 22.8, 0.54 +/- 0.1, and 53.6 +/- 25.7 mg/dl, respectively), compared to the DN group (443.8 +/- 42.72, 1.58 +/- 0.4, and 281.8 +/- 47.35 mg/dl, respectively). In addition, it exhibited elevation in the levels of Sirt-1, Nrf-2 and HO-1 compared to the DN group. Finally, Ru + SeNPs exhibited a significant reduction in IL-6, NF-KB, TNF-alpha, Jak-2, and p-Stat3 (42.8 +/- 10.3, 1.2 +/- 0.1, 53.4 +/- 3.87, 0.8 +/- 0.06 and 1.1 +/- 0.2 U/g tissue, respectively) when compared to the DN group (155.3 +/- 13.97, 2.8 +/- 0.3, 105.5 +/- 32.84, 2.03 +/- 0.2 and 2.56 +/- 0.15 U/g tissue, respectively). Therefore, combining Ru with SeNPs has a potential renoprotective effect against DN by upregulating Nrf-2/ HO-1 and downregulating Jak-2/Stat3 Pathways.

Automated summary

This study investigated the inhibitory effects of Rutin and Selenium nanoparticles on the Stat3 pathway in diabetic nephropathy. The results showed that the combination of Rutin and Selenium nanoparticles had a potential renoprotective effect. The study suggests that Rutin and Selenium nanoparticles may alleviate inflammation and kidney damage by modulating the Nrf-2/HO-1 and Jak-2/Stat3 pathways.