Testosterone and berberine co-administration inflicts renewal process in varicocele: A bridge between IL-6, TNF-α and cell renewal factor Bcl-6b

Background: Varicocele (VCL) is one of the main causes of male infertility. The tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), as multifunctional cytokines, are known to be produced in response to chronic inflammation, testosterone withdrawal and oxidative stress in varicoceles. Moreover, TNF-α and IL-6 overexpression adversely affects the spermatogonial stem cells (SCCs) renewal process. Therefore, present study was done to analyze the effect of testosterone and berberine (potent antioxidant) against VCL-induced SCCs renewal arrest by assessing testicular TNF-α, IL-6 and Bcl-6b levels.Methods: Thirty mature Wistar rats were divided to control and test groups. The animals in test group were undergone to experimental VCL. Thereafter, the test group subdivided to non-treated VCL-induced, testosterone-sole-treated (400 μg/kg), testosterone+50 mg/kg and 100 mg/kg berberine-treated groups. After 60 days, the animals euthanized and testicular levels of IL-6 and TNF-α were evaluated by using ELISA. The mRNA level of Bcl6 was assessed by using RT-PCR, and immunohistochemistry (IHC) was used to estimate positive cells distribution/one mm2 of the tissue.Result: The TNF-α and IL-6 levels was increased and the Bcl-6b expression was decreased in VCL-sole group compared to control group. However, all treated groups exhibited diminished TNF-α and IL-6 as well as enhanced Bcl-6b expression versus VCL-sole animals. Comparing all groups, the animal in testosterone+berberine (100mg/kg) exhibited better results in comparison to other groups.Conclusion: Our data shows that, the co-administration of testosterone and berberine inhibits the pro-inflammatory signals by suppressing TNF-α and IL-6 synthesis. The last event triggers the SCCs renewal pathway by Bcl-6b-related machinery.

کلیدواژه ها:

Bcl-6b ، Berberine ، IL-6 ، Testosterone ، TNF-α ، Varicocele