title: Evaluation of antimicrobial peptide nisin as a safe vaginal contraceptive agent in rabbits: in vitro and in vivo studies.
abstract: In the midst of the global epidemics of both unwanted pregnancies and sexually transmitted infections (STIs), options that provide protection are ideal. In the present study, nisin, a known antimicrobial peptide, was evaluated for safety and contraceptive potential in vitro and in vivo in the rabbit. A concentration of 400 microg nisin per ml was found to be spermicidal in vitro, and the effect was dose and time dependent. In vivo studies indicated that intravaginal application of 1 mg nisin blocked conception in rabbits. Repeated application of nisin (50 mg/animal per day) in rabbits for 14 consecutive days did not cause local inflammation or damage to the vaginal epithelium. In addition, the rate of diffusion of nisin into the blood via the vaginal mucosal epithelium, and its clearance from the circulation was found to be rapid. No treatment-related changes were observed in the reproductive performance of rabbits after cessation of treatment. Furthermore, no changes were observed in the gestation period, subsequent growth and survival of neonates in these animals. When male rats were given nisin orally for 13 consecutive weeks, no effect was observed on reproductive performance. The number of pups born, survival and growth of pups were unaltered. The affinity studies of nisin revealed that spermatozoa are more susceptible to nisin than red blood cells and vaginal epithelial cells. We suggest that nisin with spermicidal and antimicrobial properties could serve as a safe vaginal contraceptive for future therapeutic interventions in STIs.
authors.affiliation: Immunology Laboratory, National Institute for Research in Reproductive Health, Parel, Mumbai, India-400025. shrichi@rediffmail.com
authors.forename: K V R
authors.initials: KV
authors.lastname: Reddy
authors.forename: C
authors.initials: C
authors.lastname: Aranha
authors.forename: S M
authors.initials: SM
authors.lastname: Gupta
authors.forename: R D
authors.initials: RD
authors.lastname: Yedery
mesh_terms: D000042:Absorption; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D004334:Drug Administration Schedule; D005260:Female; D005298:Fertility / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D009092:Mucous Membrane / Q000378:metabolism; D009561:Nisin / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D011247:Pregnancy; D011256:Pregnancy Outcome; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013089:Spermatocidal Agents / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D014621:Vagina / Q000378:metabolism; D014622:Vaginal Creams, Foams, and Jellies
chemical_list: D000900:Anti-Bacterial Agents; D013089:Spermatocidal Agents; D014622:Vaginal Creams, Foams, and Jellies; D009561:Nisin