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"Mirabegron as a Protective Agent in Testosterone-Induced Prostate and Seminal Vesicle Toxicity: Insights into PCNA
Sarah Sameh Abdel-Hameed1, Mahmoud El-Daly2, Asmaa I Matouk1
1Department of Pharmacology& Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia National University (MNU), Minia, Egypt.
Background:
Testosterone is an androgenic hormone and one of the anabolic steroids used in the management of conditions related to hypogonadism as well as to enhance performance in bodybuilders. Prolonged use of testosterone has been linked to adverse outcomes on male reproductive organs. Mirabegron, a β3- adrenergic receptor agonist, is used to alleviate symptoms of overactive bladder and recently, it has shown substantial antioxidant and antinflammmatory effects.
Aim:
This study was designed to investigate the potential protective effects of mirabegron against testosterone induced-toxicity on prostate and seminal vesicle tissues via modulating oxidative stress, inflammation and androgenic activities.
Methods:
Male Wistar rats (200 to 250g) were divided into three groups (n = 8); control; received vehicle, testosterone; received testosterone enanthate (3mg/kg, S.C.), and testosterone + mirabegron; received testosterone (3mg/kg, S.C.) and mirabegron (10mg/kg, P.O.) concurrently. Treatments and vehicle were administrated daily for 4 weeks.
Results:
Mirabegron attenuated the testosterone-induced changes on serum levels of testosterone, FSH and LH as well as reduced prostatic 5α-reductase 1 (5AR1) (0.9433 ± 0.09597ng/mg) levels. Mirabegron improved the testosterone-induced histopathological alterations of the prostate and seminal vesicle tissues. Further, it reduced prostatic TGF-β1 level (42.93 ± 3.593pg/mg) and increased GSH content in both prostatic and seminal vesicle tissues ((25.59 ± 0.8877 and 31.70 ± 0.895 µmol/mg; respectively. Additionally, mirabegron prophylactic treatment suppressed testosterone-induced increase of oxidative stress, inflammatory and proliferative mediators, including MDA, total nitrite, iNOS, TLR4, IL-1β, PCNA, and procaspase-3.
Conclusion:
Mirabegron mitigated the damage on prostate and seminal vesicle tissues induced by testosterone through its antioxidant and anti-inflammatory activities.