{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:44:05Z","timestamp":1789548245603,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"1-4","license":[{"start":{"date-parts":[[2008,12,16]],"date-time":"2008-12-16T00:00:00Z","timestamp":1229385600000},"content-version":"vor","delay-in-days":1811,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2004,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>ROS, RNS, BRIs and ROS\u2010RNS hybrids are produced during drug or chemical metabolism<jats:italic>in vivo<\/jats:italic>. These reactive species are instrumental to the culmination of cellular oxidative stress (OS). OS, once turned on, does not spare any vital intracellular macromolecule, such as glutathione, DNA, RNA, proteins, enzymes, lipids and ATP. Since concentration gradients of such components are very delicately balanced for normal cellular functioning, a gross perturbation leads to cell injury and cell death. Abundant evidence now suggests that intracellular antioxidants keep OS in check and maintain homeostasis. Our laboratory has focused on the role of OS in orchestrating various forms of cell death during drug and chemically\u2010induced target organ toxicity and their counteraction by various natural or synthetic antioxidants in<jats:italic>in vivo<\/jats:italic>models. Despite complexity of the<jats:italic>in vivo<\/jats:italic>models, results show that metabolism of xenobiotics are invariably associated with different degrees of OS and natural antioxidants such as grape seed extract, bitter melon extract (<jats:italic>Momordica charantia<\/jats:italic>) and N\u2010acetylcysteine (NAC) which were very effective in counteracting organ toxicities by minimizing events linked to OS (lipid peroxidation and total glutathione), and CAD\u2010mediated DNA fragmentation. Phytoextract exposure rescued cells from toxic assaults, protected genomic integrity, and minimized apoptotic, necrotic and apocrotic (oncotic necrosis) cell deaths. Pre\u2010exposure mode was more effective than post\u2010exposure route. Overall scenario suggests that OS may have been the prime modulator of death and\/or survival programs, whereas, antioxidants may have imparted a dual role in either erasing death signals or reviving survival signals, and a combination of antioxidants may be more beneficial than a single entity to influence a number of intracellular events operating simultaneously to neutralize chaotic toxicological consequences.<\/jats:p>","DOI":"10.1002\/biof.552210144","type":"journal-article","created":{"date-parts":[[2008,12,19]],"date-time":"2008-12-19T01:29:34Z","timestamp":1229650174000},"page":"223-232","source":"Crossref","is-referenced-by-count":46,"title":["Oxidative stress is the master operator of drug and chemically\u2010induced programmed and unprogrammed cell death: Implications of natural antioxidants<i>in vivo<\/i>"],"prefix":"10.1002","volume":"21","author":[{"given":"S. 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D.","year":"1996","journal-title":"J. Pharm. Exp. Thera."},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00562-7"},{"key":"e_1_2_1_4_2","unstructured":"S. D.Ray Oxidative stress orchestrates both apoptosis and necrosisin vivo: a new perspective from molecular toxicology. Proc. Soc. Free Rad. Res. Chemistry Biochemistry and Pathophysiological Implications D. Galaris ed. Medimond S.R.L. Monduzzi Editore Int. Proc. Div. Italy 2003 pp.45\u201353."},{"key":"e_1_2_1_5_2","doi-asserted-by":"crossref","unstructured":"E. J.Hickey R. R.Raje V. E.Reid S. M.GrossandS. D.Ray Diclofenac\u2010Inducedin vivonephrotoxicity may involve oxidative stress mediated massive genomic DNA fragmentation and apoptotic cell death Free Radical Biology & Medicine(2001) 139\u2013152.","DOI":"10.1016\/S0891-5849(01)00560-3"},{"key":"e_1_2_1_6_2","volume-title":"Roles of Polyphenoles, Flavonoids and Oligomeric Proanthocyanidins in Cancer Chemoprevention, Chapter 21","author":"Ray S. 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