Antiapoptotic and antioxidative effects of cerium oxide nanoparticles on the testicular tissues of streptozotocin-induced diabetic rats: An experimental study

Abstract

Background: Cerium dioxide nanoparticles (CNPs) due to the antidiabetic and antioxidant activities are proposed for the treatment of oxidative stress-associated diseases.

Objective: To examine the impact of CNPs on hyperglycemia-induced apoptosis and oxidative stress in the testis of diabetic rats.

Materials and methods: Twenty-four male rats were divided into four groups (n = 6/each) as diabetic rats, CNPs group, diabetic + CNPs rats, and controls. The control group was fed only mouse food and water. Rats became diabetic through receiving streptozotocin (STZ) 60 mg/kg. CNPs were given to the rats at a dose of 30 mg/kg daily for 2 wk. Malondialdehyde and total thiol group (TTG) levels were measured using spectrofluorometer. Expression of b-cell lymphoma protein 2-associated X protein (BAX) and b-cell lymphoma protein 2 (Bcl-2) were investigated using quantitative real-time polymerase chain reaction. Western blot analysis was used to examine caspase 3 protein levels.

Results: The content of malondialdehyde significantly increased in the STZ-diabetic rats, while TTG levels demonstrated a remarkable decrease. Caspase-3, BAX, and BAX/Bcl-2 mRNA ratio raised significantly in the STZ-diabetic rats. On the other hand, Bcl-2 mRNA levels reduced in the testis of diabetic rats (p = 0.006). Intervention with CNPs caused a substantial increase in the TTG levels, while the malondialdehyde contents, caspase-3, BAX levels, as well as BAX/Bcl-2 mRNA ratio were considerably decreased following CNPs treatment. Administration of CNPs increased mRNA levels of Bcl-2 (p $<$ 0.0001).

Conclusion: CNPs treatment attenuates testicular apoptosis and oxidative stress induced by diabetes. This nanoparticle might be suggested for the treatment of diabetes-associated reproductive disorders.

Keywords: Nanoceria; Oxidative stress; Apoptosis; Diabetes; Testis..

Figure 1

Comparison of malondialdehyde (MDA) and total thiol concentrations group (TTG) concentrations between the groups. Results are presented as Mean $\pm$ SD. (A) Comparison of MDA concentration between the groups. There was a significant difference in the concentration of MDA between the control and diabetes groups (p = 0.001). Concentration of MDA demonstrated significant increase in the cerium dioxide nanoparticles (CNPs) + diabetes group when compared to the diabetes group (p = 0.032). (B) Comparison of TTG levels between the groups. TTG levels reduced significantly in the diabetes group in comparison to the control group (p $<$ 0.0001). Following the treatment with CNPs, the TTG levels increased significantly (p = 0.034).

Figure 2

B-cell lymphoma protein 2 (Bcl-2) and BCL2-associated X protein (BAX) mRNA expression and BAX/Bcl-2 mRNA ratio in the testicular tissue of experimental groups. Results are presented as Mean $\pm$ SE. (A) Expression of Bcl-2 compared between the groups. The results revealed signifcant differences between the control and diabetic groups (p = 0.006), diabetic and cerium dioxide nanoparticles (CNPs) groups (p = 0.001), and between diabetic and diabetic + CNPs groups (p $<$ 0.0001). (B) Expression of BAX compared between the groups. There were significant differences in the expression levels of BAX between the control and diabetic groups (p = 0.01), diabetic and diabetic + CNPs groups (p = 0.01), and between control and diabetic + CNPs groups (p = 0.01). (C) Comparison of BAX/Bcl-2 mRNA ratio between the groups. Significant differences were observed between the control and diabetic groups (p $<$ 0.0001), between diabetic and CNPs groups (p $<$ 0.0001), diabetic and diabetic + CNPs groups (p $<$ 0.0001), and between control and diabetic + CNPs groups (p $<$ 0.0001).

Figure 3

The effect of cerium dioxide nanoparticles (CNPs) on Caspase-3 protein concentration in the testicular tissue of experimental groups. Results are presented as Mean $\pm$ SE. (a) Difference between the control and CNPs with diabetic groups (p = 0.001). (b) Difference between the diabetic and diabetic + CNPs groups (p = 0.04).