Prevention of ochratoxin A-induced oxidative stress-mediated apoptotic processes and impairment of embryonic development in mouse blastocysts by liquiritigenin.
Environ Toxicol
; 34(5): 573-584, 2019 May.
Article
em En
| MEDLINE
| ID: mdl-30698892
ABSTRACT
Ochratoxin A (OTA), a mycotoxin constituent of a range of food commodities, including coffee, wine, beer, grains, and spices, exerts toxicological and pathological effects in vivo, such as nephrotoxicity, hepatotoxicity, and immunotoxicity. In a previous report, we highlighted the potential of OTA to induce apoptosis via reactive oxygen species (ROS) generation in mouse blastocysts that led to impaired preimplantation and postimplantation embryo development in vitro and in vivo. Here, we have shown that liquiritigenin (LQ), a type of flavonoid isolated from Glycyrrhiza radix, effectively protects against OTA-mediated apoptosis and inhibition of cell proliferation in mouse blastocysts. Preincubation of blastocysts with LQ clearly prevented OTA-triggered impairment of preimplantation and postimplantation embryonic development and fetal weight loss, both in vitro and in vivo. Detailed investigation of regulatory mechanisms revealed that OTA mediated apoptosis and embryotoxicity through ROS generation, loss of mitochondrial membrane potential (MMP), and activation of caspase-9 and caspase-3, which were effectively prevented by LQ. The embryotoxic effects of OTA were further validated in an animal model in vivo. Intravenous injection of dams with OTA (3 mg/kg/day) led to apoptosis of blastocysts, impairment of embryonic development from zygote to blastocyst stage and decrease in day 18 fetal weight. Notably, preinjection of dams with LQ (5 mg/kg/day) effectively prevented OTA-induced apoptosis and toxic effects on embryo development. Our collective results clearly demonstrate that OTA exposure via injection has the potential to damage preimplantation and postimplantation embryonic development against which LQ has a protective effect.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Blastocisto
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Apoptose
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Estresse Oxidativo
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Substâncias Protetoras
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Flavanonas
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Desenvolvimento Embrionário
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Ocratoxinas
Limite:
Animals
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Pregnancy
Idioma:
En
Revista:
Environ Toxicol
Assunto da revista:
SAUDE AMBIENTAL
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TOXICOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Taiwan