[Effect of gossypol in combination with misoprostol on termination of early pregnancy in rats and mice].
Treatment of mice with misoprostol alone at doses ranging from 200 to 6400 micrograms.kg-1, qid on day 6-8 or bid on day 9 of gestation, the rate of effective early pregnancy interruption were low and showed no dose effect relation. When giving misoprostol 200-6400 micrograms.kg-1 bid on day 9 of gestation following administration of gossypol 50 mg.kg-1 qid on day 6-8, the rate of abortion increased as the dose of misoprostol increased, and the ED50 of misoprostol was 397.8 micrograms.kg-1. The ED50 of gossypol given orally on day 6-8 of gestation was 69.4 mg.kg-1. However, when gosyypol was given in combination with misoprostol 400, 800 or 1600 micrograms.kg-1 on day 9 bid, the ED50 of gossypol decreased to 63.2, 48.6 or 34.9 mg.kg-1, respectively. The results suggest that combination of gossypol and misoprostol showed synergistic effect on termination of early pregnancy in mice. Misoprostol obviously strengthened the uterine contraction of rats both in early pregnancy and estrus in vitro. The contraceptive intensity of contraction was increased as the dose of misoprostol increased from 10(-9), 10(-8) to 10(-7) mol.L-1, and the estrus group was higher than the early pregnancy group (P < 0.01). Gossypol(10(-5)-10(-6) mol.L-1) showed no effect on the uterine activity in rats, but the sensitivity of the uterus of the early pregnant rats to misoprosrol was found to be significantly increased by treatment with gossypol on day 6-8 of gestation (P < 0.01). Degeneration of the decidual was observed under light microscopy when gossypol 80 mg.kg-1.d-1, or misoprostol 800 micrograms.kg-1.d-1, or gossypol 40 mg.kg-1.d-1 combined with misoprostol 400 micrograms.kg-1.d-1 was given orally to rats on day 6-8 of pregnancy. The degeneration of cells was more remarkable when both drugs were given in combination. The assay of immunoreactivity for PR demonstrated that the distribution and content of PR in uterine decidua had no difference between the control group and the treated groups.
Chen
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Y
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031.
Cao
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L
Gu
Z P
ZP
D000020:Abortifacient Agents, Nonsteroidal / Q000494:pharmacology; D000028:Abortion, Induced; D000818:Animals; D003271:Contraceptive Agents, Female / Q000494:pharmacology; D003656:Decidua / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006072:Gossypol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016595:Misoprostol / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects*
D000020:Abortifacient Agents, Nonsteroidal; D003271:Contraceptive Agents, Female; D016595:Misoprostol; D006072:Gossypol; C028178:gossypol acetic acid