Teratogenic effects of HESA-A, a natural anticancer product from Iran, in mice.
HESA-A is a natural product containing herbal and marine animal substances, which has been patented in Iran. It has shown antioxidant, cytotoxic and anticancer effects. The aim of this study was to evaluate the teratogenic effects of HESA-A in mice. HESA-A (50, 100, 200, 400 and 800 mg/kg) was administered orally to pregnant mice on days 6 to 14 of gestation. Mouse reproductive developmental toxicity study was performed according to the ICH guideline. Embryos from the treated dam were sectioned and studied for external morphological abnormalities and skeletal malformations. HESA-A at two doses (400 and 800 mg/kg) slowed weight gain of pregnant mice. These two doses of HESA-A led to reduction in uterus weight (17% and 20% for the 400 and 800 mg/kg doses, respectively), increase in post-implantation resorption (150% and 200%, respectively), reduction in fetus weight (22% and 32%, respectively) and crown-lump length (15% and 19%, respectively). HESA-A at 400 and 800 mg/kg doses caused mild external and skeletal malformation significantly higher than the normal saline group. However, higher doses caused embryo malformations such as short limbs, spinal abnormalities, dermal cysts, microphtalmia and cleft palate. According to this study, only higher doses of HESA-A, which are 20 to 40 times higher than the usual therapeutic doses based on body surface conversion, may cause embryonic toxicity. This provides a reasonable safety margin for the use of HESA-A in pregnancy. Mechanisms of these abnormalities are not clear and need to be determined.
Moallem
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SA
Pharmaceutical Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. moallem@mums.ac.ir
Ahmadi
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A
Moshafi
M
M
Taghavi
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MM
D000014:Abnormalities, Drug-Induced / Q000196:embryology / Q000209:etiology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D007492:Iran; D007928:Lethal Dose 50; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D028321:Plant Preparations / Q000633:toxicity*; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*
C502848:HESA-A preparation; D028321:Plant Preparations; D013723:Teratogens