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Vitamin B-12 Prevents Cimetidine-Induced Androgenic Failure and Damage to Sperm Quality in Rats

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Autor(es):
Beltrame, Flavia Luciana [1] ; de Santi, Fabiane [1] ; Vendramini, Vanessa [1] ; Lourenco Cabral, Regina Elizabeth [1] ; Miraglia, Sandra Maria [1] ; Cerri, Paulo Sergio [2] ; Sasso-Cerri, Estela [2]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Fed Univ Sao Paulo UNIFESP EPM, Dept Morphol & Genet, Sao Paulo - Brazil
[2] Sao Paulo State Univ UNESP FOAr, Dent Sch, Dept Morphol, Lab Histol & Embryol, Araraquara - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: FRONTIERS IN ENDOCRINOLOGY; v. 10, JUL 10 2019.
Citações Web of Science: 0
Resumo

Cimetidine, used as an anti-ulcer and adjuvant treatment in cancer therapy, causes disorders in the male reproductive tract, including steroidogenesis. However, its effect on sperm quality and male fertility has been poorly addressed. Since vitamin B-12 has demonstrated to recover spermatogonia number and sperm concentration in cimetidine-treated rats, we evaluated the impact of cimetidine on sperm quality and fertility potential and whether vitamin B-12 is able to prevent the harmful effect of this drug on steroidogenesis and sperm parameters. Adult male rats were treated for 52 consecutive days as follows: cimetidine group (100 mg/kg of cimetidine), cimetidine/vitamin B-12 group (100 mg/kg of cimetidine + 3 mu g vitamin B-12), vitamin B-12 group (3 mu g vitamin B-12) and control group (saline). Serum testosterone levels and immunofluorescence associated to western blot for detection of 17 beta-HSD6 were performed. Sperm morphology and motility, mitochondrial activity, acrosome integrity, DNA integrity by Comet assay, lipid peroxidation as well as fertility potential were analyzed in all groups. Apoptotic spermatids were also evaluated by caspase-3 immunohistochemistry. In the cimetidine-treated animals, reduced serum testosterone levels, weak 17 beta-HSD6 levels and impaired spermiogenesis were observed. Low sperm motility and mitochondrial activity were associated with high percentage of sperm tail abnormalities, and the percentage of spermatozoa with damaged acrosome and DNA fragmentation increased. MDA levels were normal in all groups, indicating that the cimetidine-induced changes are associated to androgenic failure. In conclusion, despite the fertility potential of rats was unaffected by the treatment, the sperm quality was significantly impaired. Therefore, considering a possible sperm-mediated transgenerational inheritance, the long term offspring health needs to be investigated. The administration of vitamin B-12 to male rats prevents the androgenic failure and counteracts the damage inflicted by cimetidine upon sperm quality, indicating that this vitamin may be used as a therapeutic agent to maintain the androgenic status and the sperm quality in patients exposed to androgen disrupters. (AU)

Processo FAPESP: 12/23845-3 - Avaliação do efeito da Vitamina B12 sobre as fases mitótica e meiótica da espermatogênese e sobre o DNA espermático de ratos tratados com cimetidina
Beneficiário:Estela Sasso Cerri
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 19/11525-3 - Vitamina B12 previne falha androgênica e danos à qualidade espermática induzidos pela cimetidina em ratos
Beneficiário:Flávia Luciana Beltrame
Linha de fomento: Auxílio à Pesquisa - Publicações científicas - Artigo
Processo FAPESP: 13/25322-0 - Efeito da cimetidina na histoarquitetura epididimária e avaliação do DNA espermático de ratos tratados com cimetidina e suplementados com Vitamina B12
Beneficiário:Flávia Luciana Beltrame
Linha de fomento: Bolsas no Brasil - Pós-Doutorado