Impact of diabetes on male sexual function in streptozotocin-induced diabetic rats: Protective role of soluble epoxide hydrolase inhibitor

Nathani Minaz,Rema Razdan,Bruce D Hammock,Somdutt Mujwar,Sumanta Kumar Goswami

doi:10.1016/j.biopha.2019.108897

Nathani Minaz, Rema Razdan + Show 3 more

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https://doi.org/10.1016/j.biopha.2019.108897

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Abstract

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.

Highlights

Sexual dysfunction (SD) refers to a problem or a group of problems occurring during any phase of the sexual response cycle, including desire, physical pleasure, arousal or orgasm, which prevents the individual from experiencing satisfactory sexual activity [1]
Treatment with t-TUCB restored the sexual function in diabetic rats as evident by an increasing in MF, IF, and EL and a decrease in ML, IL and PEI compared to diabetic control rats in a dose dependent manner (Fig. 1)
Inhibition of soluble epoxide hydrolase (sEH) prevents a decrease in the weight of sex organs from diabetic rats A decrease in the weight of testes, and penis were observed in the diabetic rats compared to normal healthy rats

Summary

Introduction

Sexual dysfunction (SD) refers to a problem or a group of problems occurring during any phase of the sexual response cycle, including desire, physical pleasure, arousal or orgasm, which prevents the individual from experiencing satisfactory sexual activity [1]. Erectile dysfunction (ED) is one of the sexual dysfunctions which, primarily, results from impairment of penile vascular and smooth muscle relaxation in multiple pathological conditions including diabetes. Endothelial dysfunction is manifested in diabetes due to alterations in many signal transduction pathways responsible for the stimulation of penile vascular and smooth muscle relaxation. Data from animal studies have shown that inhibitors of sEH attenuate endothelial dysfunction in diabetes [9]. We reported that Moringa oleifera (seed) extract inhibits sEH and augments sexual function in healthy rats [11]. Based on these studies, we hypothesized that inhibition of sEH might have a positive impact on sexual function in diabetes

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