Ellagic acid Nanoparticles Attenuate Oxidative Stress and Testicular Damage in High Fat Diet/Streptozotocin-Induced Diabetic Rats

Abstract Objectives Both forms of diabetes mellitus have several detrimental effects on the male reproductive system, including damage to the testicles and impaired spermatogenesis. This study aimed to compare the probable protective effect of ellagic acid nanoformulation (NEL), regular ellagic acid (EL), metformin (MET), and their combination on testicular damage induced by diabetes in mice. Methods Diabetes was induced in 6 groups (n=6) of BALB/c male mice by high-fat diet (HF) plus streptozotocin (STZ). The groups were treated with EL, NEL, MET, EL plus MET, and NEL plus MET. A healthy set of mice served as a control group. Results The results showed that EL possesses no antihyperglycemic activity in contrast to the NEL, which showed a significant hypoglycemic activity comparable to MET. Adding NEL to MET showed no benefit concerning the glucose-lowering activity. Both EL and NEL prevented diabetes-induced testis weight loss. Only NEL increased the testis-bodyweight ratio. Adding EL or NEL to MET improved MET therapeutic activity regarding the testis weight and testis-bodyweight ratio. Both EL and NEL and their combination with MET preserved the testicular germ cells layer and spermatogenesis with the best preservation in the combination therapy groups. EL showed no antioxidant activity, while NEL had (increased total antioxidants and decreased lipid peroxidation). Besides, adding EL and NEL to MET improved its antioxidant activity. Both EL and NEL increased PCNA immunoexpress ion in the testis, indicating spermatogenesis’s promotion with a superior activity of NEL and the combination groups. Both EL and NEL decreased caspase-3 immunoexpression in the testis, indicating inhibition of apoptosis with an equal activity of all treatment regimens. Conclusion These results indicated that nano formulation of EL improved the antihyperglycemic activity. NEL showed antioxidant activity. NEL more effectively prevented diabetes-induced testicular damage, apoptosis, and impaired spermatogenesis. These results recommended NEL as a single or combined with MET to protects against male testicular injury associated with diabetes.