Intrasperm Ca2+ modulation and human ejaculated sperm viability: influence of miconazole, clotrimazole and loperamide

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Abstract

Elevation of intrasperm Ca2+ is reported to influence viability of ejaculated spermatozoa. Human spermatozoa possess inositol triphosphate (IP3)-sensitive Ca2+ stores, which can be targeted for increasing intrasperm Ca2+ level. The influence of agents affecting Ca2+ homeostasis has been investigated. Miconazole nitrate, clotrimazole and loperamide hydrochloride produced a dose- and time-dependent decrease in viability, each requiring respectively 0.5, 1.0 and 1.0 mm for producing death of all sperm cells immediately upon addition to ejaculated human semen samples. The reduction in sperm viability was accompanied by elevation of intrasperm Ca2+ and was not affected by presence or absence of extracellular Ca2+. Significantly (P < 0.05) less time was required for producing complete loss of sperm viability and increasing intrasperm Ca2+ when any of these drugs was added to sperm cells previously treated with selected agents affecting Ca2+ homeostasis. This enhanced spermicidal activity of miconazole, clotrimazole and loperamide appeared to be due to further mobilization of Ca2+ from partially depleted intrasperm Ca2+ stores. Synergism of spermicidal activity and intrasperm Ca2+ elevation by miconazole or clotrimazole was observed when Ca2+ efflux from sperm cells was simultaneously inhibited by 2′,4′-dichlorobenzamil hydrochloride, a Na+-Ca2+ exchange inhibitor. The spermicidal activity of miconazole, clotrimazole or loperamide due to elevation of intrasperm Ca2+ and its synergism, therefore, has great potential for exploitation of these drugs as contact spermicides.

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