Inhibition of human sperm respiration by 4-hydroperoxycyclophosphamide and protection by mesna and WR-1065.
OBJECTIVE
To determine the effect of 4-hydroperoxycyclophosphamide (4OOH-CP) on the respiration of human sperm, and investigate the protective properties of mesna and WR-1065.


METHODS
SUNY Upstate Medical University, Syracuse, NY.


METHODS
Men (n = 12) visited the Andrology Department for fertility evaluation.


METHODS
None.


METHODS
Sperm respiration.


RESULTS
Immediate decline in the rate of respiration was observed when 4OOH-CP was added to washed sperm or semen. The inhibition was concentration dependent. The respiration was less affected when 4OOH-CP was added to semen, suggesting the presence of protective factors in the seminal plasma. Excess of mesna or WR-1065 ameliorated the effect of 4OOH-CP. Mesna was the more potent of the two compounds. 4OOH-CP also inhibited the respiration of mitochondria from beef heart.


CONCLUSIONS
These findings emphasize the adverse effects of alkylating agents on sperm function. The results also provide a framework for thiol drug administration with high-dose alkylating agents to protect male fertility. The protective capacity of seminal plasma deserves further testing.
Badawy
Zaki S
ZS
Department of Pediatrics, State University of New York, Upstate Medical University, Syracuse, New York 13210, USA.
Souid
Abdul-Kader
AK
D000477:Alkylating Agents / Q000494:pharmacology; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008624:Mercaptoethylamines / Q000494:pharmacology*; D015080:Mesna / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D012661:Semen / Q000187:drug effects / Q000502:physiology*; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology*
D000477:Alkylating Agents; D008624:Mercaptoethylamines; D020011:Protective Agents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D003520:Cyclophosphamide; D015080:Mesna; C011272:perfosfamide