Effect of Cerium Oxide Nanoparticles on Nrf2-Related Genes in A Rat Model of Experimental Diabetic

Backgournd: The transcription factor Nrf2 is the main regulator of antioxidant defense. It controls and induced expression of an array of defensive genes encoding detoxifying enzymes and antioxidant proteins. CeO2 nanoparticle act as direct antioxidants mediators to restrict the amount of intracellular ROS.The aim of this study was to investigate the effect of CNPs on the expression of Nrf2-dependent antioxidant response (Nrf2, HO-1, NQO1, and GCLC) in the streptozotocin (STZ) induced diabetic rats.Methods: We included 24 Adult male Wistar rats weighing 250-300 g. After a week of adaptation to the standard diet, the rats were randomly divided into four groups with six rats in each. Control group received only a standard diet. CNPs group received CNPs 30 mg/kg/daily, diabetic rats received STZ (60mg/kg/daily), rats in STZ+ CNPs group received 30mg/kg/2 weeks of CNPs following STZ injection. We assessed Nrf2, HO-1, NQO1 and GCLC expression using quantitative real-time PCR method.Results:Nrf2, HO-1, NQO1 and GCLC mRNA expression levels in diabetic rats were significantly lower than controls (p=0.01, p=0.0001, p=0.002, p=0.001, respectively).The mRNA transcript levels of Nrf2, HO-1, NQO1, and GCLC were significantly upregulated in the testes of diabetic rats treated with CNPs (all p’s=0.0001). Moreover, Nrf2 was significantly associated with NQO-1, GCLC, and HO-1 mRNA expression levels (all p’s=0.0001).Conclusions:Our results provide convincing experimental evidence that treatments with CNPs upregulates Nrf2 and its downstream antioxidant genes and can be used as a therapeutic strategy for attenuating DM-induced oxidative damage, particularly in the testicular tissue.

Keywords:

CeO2 nanoparticle , Diabetes , Nrf2 , HO-1 , NQO1 , GCLC