Abstract
Cyclophosphamide is an anti-neoplastic chemotherapy drug which, when administered to animals during the gestational period, provokes visceral, skeletal and external malformations. Copaiba oil obtained from Copaifera L. genus is traditionally used in popular medicine for its anti-inflammatory and antimicrobial activities. However, the effect of copaiba oil onteratogenesis remains unknown. This study aimed to investigate the possible protector effects of copaiba oil on the model of teratogenesis induced by cyclophosphamide in mice. Pregnant female Swiss mice were divided into 8 groups (n = 15). Three groups received copaiba oil, via gavage, in the following doses: 0.3 mL·Kg-1, 0.6 mL·Kg-1 and 0.9 mL·Kg-1 (b.w.), associated to phosphate-buffered saline (PBS), intraperitoneal (i.p.). The negative control group received medium chain triglyceride (MCT) and PBS. The positive control group received cyclophosphamide (30 mg·Kg-1 (b.w.)) and MCT. The three treatment groups called associated groups (A) received one of the doses of copaiba oil, via gavage and an associated dose of cyclophosphamide intraperitoneally. Copaiba oil presented a protective effect against teratogenesis induced by cyclophosphamide in the following skeletal structures: metacarpals, forepaws proximal phalanges, and tail vertebras. It also reduced the hydrocephalus frequency. These data suggest that copaiba oil could be a potential candidate for an anti-teratogenic agent.
Highlights
Fetal development abnormalities can be caused by drugs, pollutants, radiation and diseases that induce oxidative stress and production of free radicals [1] [2]
Ashby and co-workers showed that inhibition of the P450 cytochrome system, induction of antioxidant enzymes, or the use of antioxidant substances reduced the embryotoxic effects of cyclophosphamide and other substances known to cause oxidative stress in animal models [6]-[8] [10]
Cyclophosphamide administration induced alterations in the developmental pattern of fetuses and placentas, which were not reverted by the association with copaiba oil (Table 2)
Summary
Fetal development abnormalities can be caused by drugs, pollutants, radiation and diseases that induce oxidative stress and production of free radicals [1] [2]. Oxidative stress can be induced by cyclophosphamide, a drug used in anti-neoplastic chemotherapy and in the treatment of autoimmune diseases. In addition to direct cytotoxicity of the intermediate and final metabolic products, the drug produces teratogenic effects by inhibiting DNA synthesis and provoking apoptosis induced by oxidative stress [4]-[6]. Ashby and co-workers showed that inhibition of the P450 cytochrome system, induction of antioxidant enzymes, or the use of antioxidant substances reduced the embryotoxic effects of cyclophosphamide and other substances known to cause oxidative stress in animal models [6]-[8] [10]
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