Jan 22, 2011

Embryoprotective role of endogenous catalase in acatalasemic and human catalase-expressing mouse embryos exposed in culture to developmental and phenytoin-enhanced oxidative stress

Toxicological Sciences : an Official Journal of the Society of Toxicology
Julia P Abramov, Peter G Wells

Abstract

Reactive oxygen species (ROS) are implicated in spontaneous and xenobiotic-enhanced embryopathies, and protein therapy with exogenous catalase suggests an embryoprotective role, although embryonic catalase activity is only about 5% of adult activity. Using mutant catalase-deficient (acatalasemic, aCat) mice and transgenic mice expressing human catalase (hCat, enhanced catalase activity) compared with a confirmed outbred CD-1 mouse model, we investigated the protective importance of constitutive embryonic catalase against endogenous ROS and the ROS-initiating teratogen phenytoin in embryo culture. Vehicle-exposed aCat and hCat embryos, respectively, exhibited reduced and enhanced catalase activity compared with wild-type (WT) controls, with conversely enhanced and reduced spontaneous embryopathies. Phenytoin was embryopathic in all strains without altering catalase activity but less so in the WT embryos for the aCat and hCat strains, which exhibited about half the catalase activity of CD-1 embryos. Phenytoin, respectively, enhanced and reduced embryopathies in aCat and hCat embryos. Among aCat embryos exposed to phenytoin, embryopathies increased with decreasing catalase activity and were completely blocked by addition of exogen...Continue Reading

Mentioned in this Paper

Embryo
Embryopathies
SOAT1 gene
House mice
Oxidative Stress
Oxidative Stress Analysis
Acatalasia
Xenobiotics
Mice, Knockout
ACAT1 gene

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