Diazepam: a peripheral benzodiazepine receptor ligand, inhibits mitochondrial F-F ATPase and induces oxidative stress in goat epididymal sperm in vitro

Benzodiazepines are the most preferred anxiolytics. Their activity as anxiolytics is mediated through central – type benzodiazepine receptor (CBR), which is associated with GABAA receptors and enhances the inhibitory effect of GABA. Another type of benzodiazepine receptors called peripheral-type benzodiazepine receptors (PBR) expressed exclusively on the outer membrane of mitochondria and functions mainly with steroidogenic machinery. Besides, PBR is involved in many other functions. The main theme of the present work has emanated from recent research that PBR ligand has another target distinct from PBR, which binds to oligomycine-sensitivity conferring Protein (OSCP) of mitochondrial F-F ATPase and reduces its activity, so that increasing the cellular free radicals thus acts as an anti-proliferative and pro-apoptotic. In the present work we evaluated the effect of diazepam (Valium, a PBR ligand) on goat epididymal spermatozoa taking ROS enhancement and diminution of F-F ATPase activity in vitro as conclusive points. Results evince that diazepam decreases motility and viability of sperm, increases oxidative stress and disturbs F-F ATPase function. Increased oxidative stress is due to rise in ROS, which is imputed to defunct F-F ATPase. We are first to report the effect of diazepam on goat epididymal spermatozoa. The work concludes the deteriorating effect of diazepam on goat epididymal sperm and the results also imply that this particular action of diazepam is through binding to OSCP of sperm mitochondria. We suggest that in male diazepam users infertility could be a complication of concern. Dichotomously this effect of diazepam could be a valuable consideration in developing new contraceptive strategy.