Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore, Karnataka, India.
Department of Entomology and Nematology, and Comprehensive Cancer Center, University of California, Davis, CA, USA.
Biomed Pharmacother. 2019 Jul;115:108897. doi: 10.1016/j.biopha.2019.108897. Epub 2019 May 15.
Diabetes-induced male sexual dysfunction is associated with endothelial dysfunction. Inhibition of soluble epoxide hydrolase (sEH) is known to improve endothelial function in diabetes. Therefore, we hypothesized that sEH inhibitor (sEHI), [trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid] / t-TUCB can restore the male sexual function in diabetic rat. After one week of administration of diabetogenic agent STZ (52 mg/kg i.p) injection, diabetic rats were treated with t-TUCB (0.1 and 0.3 mg/kg, p.o) or vehicle for 8 weeks. The sexual behaviour parameters of the animals were evaluated at the end of dosing period. The levels of testosterone and glucose in serum, and sperm were quantified. Effect of treatment on weight of reproductive organs and histopathology of penile tissue was evaluated. Diabetes had a negative effect on male sexual function, weight of sexual organs and production of sperm with a parallel decrease in the level of testosterone. The sEHI, t-TUCB, significantly preserved the sexual function and minimized an increase in the level of blood glucose in diabetic rats. It also prevented a decrease in the level of testosterone and sperm in diabetic rats, in comparison to diabetic control rats. Further, diabetes induced distortion of corpus cavernosum was attenuated by t-TUCB. Based on our findings, sEHI may delay the development of sexual dysfunction in diabetes.
糖尿病引起的男性性功能障碍与血管内皮功能障碍有关。已知可溶性环氧化物水解酶（sEH）抑制剂可改善糖尿病中的血管内皮功能。因此，我们假设 sEH 抑制剂（sEHI）[反式-4-{4-[3-（4-三氟甲氧基苯基）-尿嘧啶基]环己氧基}苯甲酸] / t-TUCB 可以恢复糖尿病大鼠的男性性功能。在给予致糖尿病剂 STZ（52mg/kg ip）注射一周后，用 t-TUCB（0.1 和 0.3mg/kg，po）或载体处理糖尿病大鼠 8 周。在给药期结束时评估动物的性行为参数。定量测定血清中睾酮和葡萄糖以及精子的水平。评估治疗对生殖器官重量和阴茎组织组织病理学的影响。糖尿病对男性性功能、性器官重量和精子产生有负面影响，同时睾酮水平下降。sEHI，t-TUCB，可显著保存糖尿病大鼠的性功能，并最大程度地降低糖尿病大鼠的血糖水平升高。它还可以防止糖尿病大鼠的睾酮和精子水平下降，与糖尿病对照组大鼠相比。此外，t-TUCB 减轻了糖尿病引起的海绵体的扭曲。根据我们的发现，sEHI 可能会延迟糖尿病中性功能障碍的发展。
