Synergistic effect of nano-selenium and metformin on type 2 diabetic rat model: Diabetic complications alleviation through insulin sensitivity, oxidative mediators and inflammatory markers

Abstract

Background and objectives In the present article, we explore a novel strategy of selenium nanoparticles (Se-NPs) for the treatment of type 2 diabetes mellitus (T2DM) by investigating the effect of Se-NPs alone and in combination with standard anti-diabetic drug metformin (MET) in high-fat diet/streptozotocin (HFD/STZ)-induced T2DM. Methods HFD was supplemented daily to experimental rats for 8 weeks, followed by a single low dose injection of 35 mg/kg of STZ to induce T2DM. The synergistic effect of the different therapeutic strategies on diabetic complications was evaluated after the Se-NPs and MET administration for 8 weeks. Molecular and biochemical analyses were conducted to figure out the effectiveness of our treatment on insulin sensitivity, oxidative mediators and inflammatory markers. Results Our observations demonstrated that HFD/STZ-induced rats have a toxic effect on serum and hepatic tissues resulted in inducing remarkable oxidative damage and hyper-inflammation with a significant disturbance in the insulin signaling pathway. Experimental animals either treated with mono-therapeutic-two doses Se-NPs (0.1 and 0.4 mg/kg) and/or MET (100 mg/kg) alone as well as the combined therapy resulted in a remarkable protective anti-diabetic effect illustrated by significant decreases in fasting blood glucose and insulin levels after 8 weeks treatment. At the same time, the levels of active insulin signaling proteins pIRS1/pAKT/pGSK-3β/pAMPK were significantly improved. Moreover, Se-NPs exhibited an anti-inflammatory effect by the mitigation of cytokine expression and a balance between oxidative stress and antioxidant status was restored. Furthermore, the anti-diabetic drug MET administration also exhibited a significant improvement in diabetic complications after the treatment period. Conclusion This study provides mightily the mechanism of action of combined Se-NPs and MET as a promising therapeutic alternative that synergistically alleviates most of diabetic complications and insulin resistance.

Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus

“…Additionally, Abdulmalek and Balbaa in 2019 examined the potential of selenium and found that it promoted insulin sensitivity by ameliorating inflammation and oxidative stress in diabetic rats [140]. These data complement the results of basic studies suggesting oxidative stress induces insulin resistance and DM [97,123,132,137,139,140]. Whilst relatively few, there is clinical evidence supporting the animal studies [141].…”

Hypoglycemic potential of selenium nanoparticles capped with polyvinyl-pyrrolidone in streptozotocin-induced experimental diabetes in rats

“…These findings were comparable to the findings of Vural et al (2017), who treated diabetic rats with sodium selenite and glucose levels decreased and remained low for seven weeks. Se is an insulin mimetic, which explains its ability to reduce the levels of glucose (Abdulmalek and Balbaa, 2019). According to Hwang et al (2007), Se increases the transport of glucose because it has insulin-like activity both in vitro and in vivo.…”

Selenium nanoparticles and metformin ameliorate streptozotocin-instigated brain oxidative-inflammatory stress and neurobehavioral alterations in rats

“…Previous studies demonstrated that low doses of selenium could exhibit antidiabetic and insulin-mimetic activities in animal models (Steinbrenner et al 2011;Al-Quraishy et al 2015;Abdulmalek and Balbaa 2019;Ebokaiwe et al 2019Ebokaiwe et al , 2020a. However, clinical interventions using selenium as a drug are contradictory, as low doses acute exposure show efficacy whereas high doses and long-term usage worsen diabetes by increasing insulin resistance (Thomson 2004;Steinbrenner et al 2011;Fontenelle et al 2018).…”

“…The emerging influence of nanotechnology as well as reported biological activities of nano-sized materials by ameliorating several metabolic disorders (Al-Quraishy et al 2015;Abdulmalek and Balbaa 2019;Ebokaiwe et al 2019Ebokaiwe et al , 2020a prompted the current study on SeNPs. Also, recent developments in nanotechnological advancement have resulted in the nano-sizing of dietary trace elements with proven biological significance such as Se nanoparticles (SeNPs).…”

“…Also, recent developments in nanotechnological advancement have resulted in the nano-sizing of dietary trace elements with proven biological significance such as Se nanoparticles (SeNPs). These have garnered recognition in the management of metabolic disorders owing to their functions as composites of some enzymes and proteins in the biological system (Rayman and Stranges 2013;Abdulmalek and Balbaa 2019;Ebokaiwe et al 2019Ebokaiwe et al , 2020a.…”