The free radical spin trapping agent phenylbutylnitrone reduces fetal brain DNA oxidation and postnatal cognitive deficits caused by in utero exposure to a non-structurally teratogenic dose of ethanol: A role for oxidative stress

Toxicity assessment due to sub-chronic exposure to individual and mixtures of four toxic heavy metals

“…Strong correlations were found among MDA, SOD, TAOC and CAT, implying an association of these in brain and kidneys of mice in the study. Oxidative stress is basically an imbalance between the production of reactive oxygen species and the body's ability to detoxify them through neutralization of antioxidants [46]. Elevated ROS results in oxidative damage to cellular macromolecules and altered signal transduction [47] .…”

Embryonic catalase protects against ethanol embryopathies in acatalasemic mice and transgenic human catalase-expressing mice in embryo culture

“…While not measured herein, our laboratory has previously shown that the mutant aCat mice used herein have 40% lower levels of catalase activity compared with WT catalase-normal embryos of the same strain (Abramov and Wells, 2011a), and in in vivo studies exhibit enhanced embryonic DNA oxidation and birth defects when treated with EtOH (Miller et al, 2013b) or phenytoin (Abramov and Wells, 2011a). Conversely, hCat mice have 40% higher levels of catalase activity compared with WT catalase-normal embryos of the same strain (Abramov and Wells, 2011a) and are protected against embryonic DNA oxidation and birth defects caused by both EtOH in vivo (Miller et al, 2013b) and phenytoin in vivo and in embryo culture (Abramov and Wells, 2011a).…”

“…Previous in vivo studies using these genetically altered animal models showed that maternal EtOH treatment caused an increase in oxidatively damaged DNA in the WT animals for all strains, and EtOHinitiated DNA oxidation was respectively decreased and increased in hCat and aCat embryos compared to their EtOH-exposed WT controls (Miller et al, 2013b).…”

“…Similarly, an embryoprotective effect has been observed with exogenous protein therapy in several models, in which pretreatment using exogenous forms of catalase or SOD reduced the developmental toxicity of ROS-initiating teratogens and conditions such as phenytoin, ethanol and diabetes in vivo and/or in embryo culture in mice, rats or Xenopus (Winn and Wells, 1995;Cederberg and Eriksson, 1997;Chen et al, 2004;Peng et al, 2004;Miller et al, 2013b). Although administration of exogenous forms of catalase is protective, the protective efficacy of the low embryonic level of the endogenous enzyme against EtOH embryopathies is unclear.…”

“…In vivo, EtOH has been shown to be a developmental toxicant in rats (Lee et al, 2005;Wentzel and Eriksson, 2008) and mice (Wentzel and Eriksson, 2006;Dong et al, 2010;Miller et al, 2013b), resulting in a spectrum of structural birth defects similar to those observed in humans. EtOH can also cause embryopathies in rats and mice in whole embryo culture (Brown et al, 1979;Priscott, 1982;Wynter et al, 1983;Snyder et al, 1992;Hunter et al, 1994;Lee et al, 2005;Xu et al, 2005), a model that removes the confounding effects of maternal factors, allowing for a more definitive examination of embryonic mechanisms of toxicity (New, 1978).…”