Embryotoxic effects of misoprostol in the mouse.
Misoprostol (MSP) is a synthetic prostaglandin E1 methyl analogue indicated for the prevention of gastric ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Because of its abortifacient properties, MSP has been extensively misused for abortion induction in Brazil. Since abortion induction with MSP very often fails and pregnancy continues to term, there has been increasing concern regarding the potential teratogenicity of this PGE1 analogue in humans. The objective of the present study was to evaluate the embryotoxicity of MSP in mice. A single dose of MSP (20 or 30 mg/kg body weight) was administered to Han:NMRI mice (ca 60 days old) by gavage on day 10 of pregnancy. The number of treated mice was as follows: control, 19; MSP 20 mg/kg, 10; MSP 30 mg/kg, 28. Cesarean sections were performed on day 18 of pregnancy and the number of resorptions and implantation sites were recorded. Fetuses were weighed, examined for external malformations, fixed, cleared and stained with Alizarin Red S for skeleton evaluation. No evidence of embryotoxicity was found at the lower dose tested. A slight and reversible deficit in pregnancy weight gain (day 10-11: control, 1.3 +/- 0.3 g; MSP 20 mg/kg, -0.9 +/- 0.9 g; MSP 30 mg/kg, -1.7 +/- 0.6 g) was the only sign of maternal toxicity noted in both groups of mice treated with misoprostol.(ABSTRACT TRUNCATED AT 250 WORDS)
Paumgartten
F J
FJ
Departamento de Farmacologia e Toxicologia, Instituto Nacional de Controle de Qualidade em Saúde, Rio de Janeiro, Brasil.
Magalhães-de-Souza
C A
CA
de-Carvalho
R R
RR
Chahoud
I
I
D000014:Abnormalities, Drug-Induced; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D008815:Mice, Inbred Strains; D016595:Misoprostol / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D015430:Weight Gain / Q000187:drug effects
D000897:Anti-Ulcer Agents; D016595:Misoprostol