The Potential Role of Zinc Oxide Nanoparticles in MicroRNAs Dysregulation in STZ-Induced Type 2 Diabetes in Rats

Abstract

Diabetes mellitus (DM) is a group of metabolic disorders that are characterized by a loss of glucose homeostasis and insufficiency in production or action of insulin. Development of newly antidiabetic molecules using a variety of organic compounds and biomolecules has been in practice for a long time. Recently, nanomaterials are also being used in antidiabetic studies for their unique properties. In this context, zinc nanoparticles have drawn attention due to the relationship between diabetes and imbalance of zinc homeostasis. Few studies have attempted to investigate the effect of zinc oxide nanoparticles (ZON) in microRNA dysregulations in diabetes. To evaluate the therapeutic effect of ZON on streptozotocin (STZ)-induced diabetic rats as well as its role in microRNA dysregulations. Diabetes was induced in rats by 60 mg/kg body weight (bwt) of STZ and then treated with ZON (5 mg/kg bwt) for 15 consecutive days. The levels of glucose, insulin, oxidative stress markers, and microRNAs expression were measured in liver and pancreas tissues. Intraperitoneal injection of 60 mg/kg bwt of STZ to Wistar rats caused significant decreases in the body weight and Zn contents of pancreas, liver, and kidney. Also, STZ injection increased the blood glucose level and oxidative stress (lipid peroxidation (LPO) and nitric oxide (NO). Meanwhile, STZ decreased blood insulin and pancreatic anti-oxidants. STZ also resulted in β cell dysfunction and destruction and altered the expression of certain pancreatic and liver microRNAs. ZON treatment for 15 days, at a dose of 5 mg/kg bwt resulted in marked improvements in the blood insulin, glucose tolerance, and structure and function of the pancreatic β cells. Furthermore, ZON administration reduced LPO and NO, and increased the levels of enzymatic and non-enzymatic anti-oxidants in STZ-induced diabetic rats. It was found also that ZON specifically regulated the expression of pancreatic and liver microRNAs that involved in diabetes development. The obtained results revealed that ZON is a promising antidiabetic agent. The antidiabetic effect of ZON was partially mediated by restoring the oxidants/antioxidants balance and by modulating the alerted microRNAs.