ABSTRACT The diterpene kaurenoic acid (KA) isolated from the oleoresin of Amazonas traditional medicinal plant Copaifera langsdorffii demonstrates interesting biological properties such as the anti-inflammatory, hypotensive, hypoglycemic and diuretic effects in vivo and the antimicrobial, smooth muscle relaxant, and cytotoxic actions in vitro. In COX-enzyme assays, KA exhibits a non-selective inhibition of cyclooxygenase (COX) isoforms, COX-1 and COX-2. Since both selective and non-selective COX-inhibitors were shown to be anti-inflammatory and exert prenatal toxicity, the present study was aimed to assess the reproductive toxicity potential of KA in mice. Mice were treated by oral gavage with KA (25 and 50 mg/kg) from Day 1 to Day 7 or Day 8 to Day 15 of pregnancy. Necroscopies were performed on Day 10 to note the number of implantation sites and the proportion of animals pregnant, or Day 20 for gestational outcome and the live fetuses were examined for gender, external, visceral and skeletal malformation and variations. The results show that KA at the highest dose tested (50 mg/kg, p.o.), interferes with the nidation process and also cause post-implantation loss, without the signs of maternal toxicity. In addition, an increased frequency of fetal skeleton variations was seen but did not cause embryo deaths or other malformations at any dose level. Our results indicate that kaurenoic acid at a dose of 50 mg/kg impairs fertility in mice, possibly through a COX-inhibitory mechanism.
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