4.4 Article

Studies on teratogenic effect of ochratoxin A given via mouldy diet in mice in various sensitive periods of the pregnancy and the putative protection of phenylalanine

Journal

TOXICON
Volume 210, Issue -, Pages 32-38

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.toxicon.2022.02.012

Keywords

Ochratoxin A; Phenylalanine; Teratogenic effect; Mice; Teratogenicity; Sensitive periods of pregnancy

Funding

  1. European Community [MOIF-CT-2005-018674, PIRSES-GA-2012-316067]
  2. UK Royal Society Joint Project with Central and Eastern Europe
  3. Foundation of the Ministry of Science and Education of Bulgaria

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Embryotoxic and teratogenic effects were observed in pregnant Swiss albino mice treated with OTA, with the strongest effects seen at OTA contamination levels of 20 ppm. Main malformations induced by OTA were observed in craniofacial structures, while a protective effect against OTA's harmful effects was observed with phenylalanine.
Embryotoxic and teratogenic effects were found in OTA-treated pregnant Swiss albino mice, which were particularly strong at OTA contamination levels of 20 ppm (corresponding to 2.8 mg OTA/kg bw per day), when fed between the day 7 and day 12 of the pregnancy. Slighter embryotoxic and teratogenic effects were found when OTA was given up to day 7 or after day 12 of mice pregnancy. The feed levels of 10 ppm OTA (corresponding to 1.4 mg OTA/kg bw per day) have a significantly weaker embryotoxic and teratogenic effects on pregnant mice and no such effects were found at 5 ppm OTA (corresponding to 0.7 mg OTA/kg gt per day). The main OTA-induced malformations wre seen in the craniofacial structures, e.g. anophthalmia, monophthalmia, microphthalmia, astomia, microstomia, maxillary hypoplasia, microcephaly, macrocephaly, in newborn mice as compared to OTA-induced somatic malformations, e.g. peromelia, micromelia, spina bifida and facial cleft. Phenylalanine given at 20 ppm in the diet was found to have a protective effect against embryotoxic and teratogenic effects of OTA.

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