ABSTRACT
The present study was performed to show the ameliorative effect of berberine (BBR), as an antioxidant and anti-inflammatory agent, against experimental varicocele (VCL)-induced molecular and histological damages. For this purpose, 50 mature Wistar rats were divided into control, control-sham, VCL-sole, 50 mg/kg and 100 mg/kg BBR-treated VCL-induced groups. The tissue levels of interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), nitric oxide (NO), total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD) and gluthatione peroxidase (GSH-px) as well as the mRNA levels of testicular CuZn SOD, MnSOD, EC-SOD and GSH-px were evaluated. The serum concentration of testosterone and germ cells mRNA damage were analysed. Finally, the sperm viability, motility, DNA integrity and chromatin condensation were analysed. Observations revealed that, the BBR significantly downregulated VCL-increased IL-6, TNF-α and NO levels, upregulated the CuZn SOD, MnSOD, EC-SOD and GSH-px mRNA level, decreased testicular MDA content, enhanced serum testosterone level and ameliorated testicular TAC, SOD and GSH-px levels. The animals in BBR-treated groups exhibited diminished mRNA damage versus non-treated VCL-induced group. The BBR has significantly (p < 0.05) improved sperm parameters. In conclusion, the BBR by promoting testicular antioxidant potential and by downregulating inflammatory reactions fairly promotes spermatogenesis and upregulates the sperm quality.
Subject(s)
Antioxidants/pharmacology , Berberine/pharmacology , Inflammation/drug therapy , Oxidative Stress/drug effects , Spermatozoa/drug effects , Testis/drug effects , Varicocele/metabolism , Animals , Antioxidants/therapeutic use , Berberine/therapeutic use , Cytokines/metabolism , Inflammation/metabolism , Inflammation/pathology , Male , Malondialdehyde/metabolism , Rats , Rats, Wistar , Semen Analysis , Spermatozoa/metabolism , Spermatozoa/pathology , Superoxide Dismutase/metabolism , Testis/metabolism , Testis/pathology , Testosterone/blood , Varicocele/pathologyABSTRACT
BACKGROUND: Varicocele is present in 10-20% of the male infertile population. PURPOSE: Present study was done to demonstrate the reinforcing effect of berberine (BBR), as an antioxidant and anti-inflammatory agent, on Sertoli cells-related niche and spermatogonial stem cells (SSCs) self-renewal in experimentally-induced VCL condition. STUDY DESIGN: 50 mature male Wistar rats were divided into control, control-sham, non-treated VCL-induced, 50â¯mg kg-1 and 100â¯mg kg-1 BBR-treated VCL-induced groups. METHODS: The Leydig and Sertoli cells distribution and Leydig cells steroidogenic activity, expression of glial cell line-derived neurotrophic factor (GDNF), proto-oncogene Rearranged during Transfection (c-RET) receptor, Ets variant gene 5 (Etv5) and B-cell chronic lymphocytic leukemia (CLL)/lymphoma 6, member B (Bcl-6b) at mRNA and protein levels were analyzed. The mRNA integrity and DNA fragmentation were assessed. Finally, the serum levels of testosterone, inhibin B and testicular total antioxidant capacity, total thiol molecules, catalase, and malondialdehyde were evaluated. RESULTS: Observations revealed that, the BBR significantly enhanced VCL-reduced Leydig and Sertoli cells population, maintained Leydig-Sertoli cells network, enhanced GDNF, c-RET Etv5 and Bcl6b expression, up-regulated testicular antioxidant and endocrine status. CONCLUSION: The BBR by boosting Leydig-Sertoli cells network up-regulates the GDNF, Etv5 and Bcl-6b expression/synthesis in SSCs, which in turn improves SSCs self-renewal activities. Thus, the BBR could be considered as an appropriate agent for antioxidant therapy of VCLs. However, more studies with bigger sample number and focus on BBR-induced effects on other genes involving in the self-renewal process are needed to have more deterministic results.
