{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T23:12:18Z","timestamp":1773097938958,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":2470,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2002,5]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>We evaluated the effects of the phenothiazine derivative thioridazine on mechanisms of mitochondria potentially implicated in apoptosis, such as those involving reactive oxygen species (ROS) and cytochrome <jats:italic>c<\/jats:italic> release, as well as the involvement of drug interaction with mitochondrial membrane in these effects.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Within the 0\u2003\u2013\u2003100\u2003\u03bc<jats:sc>M<\/jats:sc> range thioridazine did not reduce the free radical 1,1\u2010diphenyl\u20102\u2010picryl\u2010hydrazyl (DPPH) nor did it chelate iron.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>However, at 10\u2003\u03bc<jats:sc>M<\/jats:sc> thioridazine showed important antioxidant activity on mitochondria, characterized by inhibition of accumulation of mitochondria\u2010generated O<jats:sub>2<\/jats:sub><jats:sup>\u2022\u2212<\/jats:sup>, assayed as lucigenin\u2010derived chemiluminescence, inhibition of Fe<jats:sup>2+<\/jats:sup>\/citrate\u2010mediated lipid peroxidation of the mitochondrial membrane (LPO), assayed as malondialdehyde generation, and inhibition of Ca<jats:sup>2+<\/jats:sup>\/<jats:italic>t<\/jats:italic>\u2010butyl hydroperoxide (<jats:italic>t<\/jats:italic>\u2010BOOH)\u2010induced mitochondrial permeability transition (MPT)\/protein\u2010thiol oxidation, assayed as mitochondrial swelling.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Thioridazine respectively increased and decreased the fluorescence responses of mitochondria labelled with 1\u2010aniline\u20108\u2010naphthalene sulfonate (ANS) and 1\u2010(4\u2010trimethylammonium phenyl)\u20106 phenyl 1,3,5\u2010hexatriene (TMA\u2010DPH).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The inhibition of LPO and MPT onset correlated well with the inhibition of cytochrome <jats:italic>c<\/jats:italic> release from mitochondria.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We conclude that thioridazine interacts with the inner membrane of mitochondria, more likely close to its surface, acquiring antioxidant activity toward processes with potential implications in apoptosis such as O<jats:sub>2<\/jats:sub><jats:sup>\u2022\u2212<\/jats:sup> accumulation, as well as LPO, MPT and associated release of cytochrome <jats:italic>c<\/jats:italic>.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2002) <jats:bold>136<\/jats:bold>, 136\u2013142; 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