RESUMO
Microbial infections, localized as well as systemic, are known to cause transitive or permanent male infertility. However, the mechanisms of infection-induced infertility are largely unknown. Earlier reports showed that steroidogenesis and spermatogenesis are affected during bacterial lipopolysaccharide (LPS)-induced acute inflammation. The present study used an LPS rat model to investigate the role of oxidative stress in spermatogenesis. Intraperitoneal administration of bacterial LPS (5mg/kg body weight) to adult male albino rats elevated testicular malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE), and decreased the activities of testicular antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. The GSH/GSSG ratio also decreased significantly. Time series analysis revealed transitory oxidative stress and expression of inflammatory mediators such as interleukin-1beta (IL-1beta), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) from 3h to 12h after LPS. Testicular expression of steroidogenic acute regulatory (StAR) protein decreased to 24h, in correlation with damage to spermatogenesis. These data are consistent with oxidative stress as a major causal factor in altered steroidogenesis, spermatogenesis, and perhaps male infertility during endotoxin-induced acute inflammation.
Assuntos
Endotoxemia/metabolismo , Infecções por Escherichia coli/metabolismo , Infertilidade Masculina/metabolismo , Lipopolissacarídeos/efeitos adversos , Estresse Oxidativo , Espermatogênese , Testosterona/metabolismo , Animais , Catalase/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Endotoxemia/complicações , Endotoxemia/fisiopatologia , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/fisiopatologia , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Imuno-Histoquímica , Infertilidade Masculina/etiologia , Infertilidade Masculina/fisiopatologia , Interleucina-1/genética , Interleucina-1/metabolismo , Peroxidação de Lipídeos , Masculino , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Oxidantes/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Superóxido Dismutase/metabolismo , Testículo/metabolismo , Testículo/patologiaRESUMO
The purpose of this study was to identify compounds that could potentially be useful for vas irrigation at the time of vasectomy. We studied the in vitro effects of a group of membrane-active and ion-channel blocking agents on human sperm motility, viability and cervical mucus penetration. Diltiazem, an anti-arrhythmic drug, and methylene blue, an agent commonly used in vasography, showed the most promising effects with marked reduction of sperm motility and cervical mucus penetration after incubation with sperm for a short period of 15 min. Diltiazem was more effective than methylene blue in inhibiting the motility and viability of sperm. Furthermore, unlike methylene blue, diltiazem significantly compromised sperm viability. Other compounds studied, such as lidocaine, nicardipine and Neosporin((R)), showed only partial inhibitory activity. Based on the data reported herein, both diltiazem and methylene blue appear to be suitable candidates to be developed for vas irrigation at the time of vasectomy.