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Cocaine treatment significantly increased superoxide dismutase activity in as little as 1\u00a0hour, with a maximum level at 6\u00a0hours in wild\u2010type mice, while significantly decreasing GPx activity and subsequently inducing oxidative damage (i.e., reactive oxygen species, lipid peroxidation and protein carbonylation). These changes were more prominent in the mitochondrial fraction than in the cytosolic fraction. In contrast, genetic overexpression of GPx\u20101 significantly attenuated cocaine\u2010induced oxidative damage in mice. Cocaine treatment significantly increased alanine aminotransferase and aspartate aminotransferase levels in the serum. Consistently, cocaine significantly enhanced cleaved caspase\u20103 expression and intramitochondrial Ca<jats:sup>2+<\/jats:sup>, while significantly reducing mitochondrial transmembrane potential. Cocaine treatment potentiated cleavage of protein kinase C \u03b4 (PKC<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27623093\">\u03b4<\/jats:ext-link>), mitochondrial translocation of PKC<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27623093\">\u03b4<\/jats:ext-link>, cytosolic release of cytochrome <jats:italic>c<\/jats:italic> and activation of caspase\u20103, followed by hepatopathologic changes. These results were more prominent in GPx\u20101 knockout than in wild\u2010type mice, and they were less pronounced in overexpressing transgenic than in non\u2010transgenic mice. Combined, our results suggest that the GPx\u20101 gene possesses protective potential against mitochondrial oxidative burden, mitochondrial dysfunction and hepatic degeneration induced by cocaine and that the protective mechanisms are associated with anti\u2010apoptotic activity via inactivation of PKC<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27623093\">\u03b4<\/jats:ext-link>.<\/jats:p>","DOI":"10.1002\/jat.3666","type":"journal-article","created":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T01:18:27Z","timestamp":1532049507000},"page":"1502-1520","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Protective potential of glutathione peroxidase\u20101 gene against cocaine\u2010induced acute hepatotoxic consequences in mice"],"prefix":"10.1002","volume":"38","author":[{"given":"Huynh 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