Matches in SemOpenAlex for { <https://semopenalex.org/work/W2070201210> ?p ?o ?g. }
- W2070201210 endingPage "53" @default.
- W2070201210 startingPage "38" @default.
- W2070201210 abstract "A comprehensive reaction schema for oxidative cytotoxicity is presented, integrating known chemical mechanisms of oxygen radical reactions and observed pathophysiology. The key features of the schema are the coupling of (1) redox cycling of autoxidizable substrates to form the equilibrium pair of superoxide anion (O−2)/and its conjugate acid, perhydroxyl radical (HO2); (2) hydrogen peroxide (H2O2) generation via O−2 dismutation; (3) catalytic redox cycling of metals reducing H2O2 to reactive hydroxyl radicals (OH); (4) direct reaction of OH with target molecules, including critical cell macromolecules and polyunsaturated lipids in membranes; (5) transfer of oxidative potential from initial to distant sites via H2O2 and O−2/HO2 diffusion, lipid free radical chain peroxidations in membranes, and migration of non-radical lipid oxidation products; and (6) cytotoxic damage at those distant sites mediated by reaction of lipid radical species and other lipid oxidation products with critical target molecules (proteins, DNA, etc.). Although there is a broad consensus of agreement within the cognizant research community concerning many aspects of this schema, there exists considerable controversy and/or misconception about several important issues. In this paper critical analyses of four presently controversial points are put forth. (1) The question of metal-dependency of Fenton generation of OH is considered first and data are presented to show that previous observations of apparent H2O2 decomposition by various semiquinone radicals most likely resulted from trace metal contamination. (2) The strong electrophile from H2O2 reduction has sometimes been ascribed to a non-free “crypto-hydroxyl” radical because of failure of traditional scavengers to inhibit its reactions in the expected ways or it has been ascribed to iron-oxy complexes based on similar “atypical” scavenger patterns plus requirements for preformed ferric iron. The behavior of these species in multiphasic, inhomogeneous systems, which is alleged to be inconsistent with that characteristic of OH, is reconciled with the competitive kinetics expected of OH in three situations: (a) compartmentalization at the cellular level (i.e., in vesicles or their membranes) which prevents access of scavengers to the sites of OH generation, (b) site-specificity at the molecular level (OH reaction occurring within a few Angstroms of specific metal-binding sites on macromolecules or in/on membranes), and (c) reactivity of secondary radicals formed by the “scavenging” of OH. (3) The significance of lipids in propagating oxidative damage from the initiation sites of lipid peroxidation to distant sensitive target molecules (proteins and nucleic acids) is discussed, along with the capability of O−2 and H2O2 to serve similar roles in propagating damage from the sites of autoxidation. (4) Finally, some common misinterpretations regarding “scavengers” and inhibitors of oxygen radical reactions from both chemical and metabolic/physiological standpoints are considered in the context of medical implications and applications." @default.
- W2070201210 created "2016-06-24" @default.
- W2070201210 creator A5040373754 @default.
- W2070201210 creator A5058844360 @default.
- W2070201210 date "1984-01-01" @default.
- W2070201210 modified "2023-09-24" @default.
- W2070201210 title "Cytotoxicity from Coupled Redox Cycling of Autoxidizing Xenobiotics and Metals: A Selective Critical Review and Commentary on Work-in-Progress" @default.
- W2070201210 cites W1481365128 @default.
- W2070201210 cites W1526682279 @default.
- W2070201210 cites W1548078249 @default.
- W2070201210 cites W1554009894 @default.
- W2070201210 cites W1840403032 @default.
- W2070201210 cites W1917517429 @default.
- W2070201210 cites W1918246468 @default.
- W2070201210 cites W1923535459 @default.
- W2070201210 cites W1955274404 @default.
- W2070201210 cites W1964687471 @default.
- W2070201210 cites W1969965042 @default.
- W2070201210 cites W1970010697 @default.
- W2070201210 cites W1970496775 @default.
- W2070201210 cites W1971391254 @default.
- W2070201210 cites W1978447098 @default.
- W2070201210 cites W1978896699 @default.
- W2070201210 cites W1982167041 @default.
- W2070201210 cites W1987343124 @default.
- W2070201210 cites W1990230868 @default.
- W2070201210 cites W1995343884 @default.
- W2070201210 cites W1999200892 @default.
- W2070201210 cites W2008574551 @default.
- W2070201210 cites W2014333187 @default.
- W2070201210 cites W2020392064 @default.
- W2070201210 cites W2022199614 @default.
- W2070201210 cites W2028709526 @default.
- W2070201210 cites W2031425666 @default.
- W2070201210 cites W2031700878 @default.
- W2070201210 cites W2038129571 @default.
- W2070201210 cites W2038251049 @default.
- W2070201210 cites W2039323398 @default.
- W2070201210 cites W2040706107 @default.
- W2070201210 cites W2049636946 @default.
- W2070201210 cites W2051580798 @default.
- W2070201210 cites W2058351695 @default.
- W2070201210 cites W2064069177 @default.
- W2070201210 cites W2065692428 @default.
- W2070201210 cites W2074477605 @default.
- W2070201210 cites W2075104158 @default.
- W2070201210 cites W2080996664 @default.
- W2070201210 cites W2088624681 @default.
- W2070201210 cites W2098621632 @default.
- W2070201210 cites W2115381431 @default.
- W2070201210 cites W2118432317 @default.
- W2070201210 cites W2132826785 @default.
- W2070201210 cites W2136935856 @default.
- W2070201210 cites W2145674512 @default.
- W2070201210 cites W2155697374 @default.
- W2070201210 cites W2163946974 @default.
- W2070201210 cites W2199918666 @default.
- W2070201210 cites W2203518542 @default.
- W2070201210 cites W2312510808 @default.
- W2070201210 cites W2329267027 @default.
- W2070201210 cites W2399000085 @default.
- W2070201210 cites W2418036390 @default.
- W2070201210 cites W3004510528 @default.
- W2070201210 doi "https://doi.org/10.1002/ijch.198400007" @default.
- W2070201210 hasPublicationYear "1984" @default.
- W2070201210 type Work @default.
- W2070201210 sameAs 2070201210 @default.
- W2070201210 citedByCount "159" @default.
- W2070201210 countsByYear W20702012102013 @default.
- W2070201210 countsByYear W20702012102014 @default.
- W2070201210 countsByYear W20702012102015 @default.
- W2070201210 countsByYear W20702012102016 @default.
- W2070201210 countsByYear W20702012102017 @default.
- W2070201210 countsByYear W20702012102019 @default.
- W2070201210 countsByYear W20702012102020 @default.
- W2070201210 countsByYear W20702012102021 @default.
- W2070201210 countsByYear W20702012102022 @default.
- W2070201210 crossrefType "journal-article" @default.
- W2070201210 hasAuthorship W2070201210A5040373754 @default.
- W2070201210 hasAuthorship W2070201210A5058844360 @default.
- W2070201210 hasConcept C139066938 @default.
- W2070201210 hasConcept C161790260 @default.
- W2070201210 hasConcept C178790620 @default.
- W2070201210 hasConcept C185592680 @default.
- W2070201210 hasConcept C21951064 @default.
- W2070201210 hasConcept C2776778087 @default.
- W2070201210 hasConcept C48349386 @default.
- W2070201210 hasConcept C50027330 @default.
- W2070201210 hasConcept C533411734 @default.
- W2070201210 hasConcept C55493867 @default.
- W2070201210 hasConcept C55904794 @default.
- W2070201210 hasConcept C75473681 @default.
- W2070201210 hasConceptScore W2070201210C139066938 @default.
- W2070201210 hasConceptScore W2070201210C161790260 @default.
- W2070201210 hasConceptScore W2070201210C178790620 @default.
- W2070201210 hasConceptScore W2070201210C185592680 @default.
- W2070201210 hasConceptScore W2070201210C21951064 @default.
- W2070201210 hasConceptScore W2070201210C2776778087 @default.