title: Supplementation with antioxidants fails to increase the total antioxidant capacity of several cell lines in culture.
abstract: Low molecular weight antioxidants (LMWA) supplements are a popular and routine approach to assist the cell and the whole organism to cope with increasing oxidative stress. Numerous experiments have been conducted in which exogenous antioxidants were supplemented to cells, animals and humans to prevent and delay pathological disorders associated with reactive oxygen species. Recently, many meta-analysis publications have demonstrated the failure of this approach and in some cases even showed an increase in the severity of the disease and all-cause mortality. The reasons for the lack of success are not fully understood and the concept of antioxidant therapy is questionable. We suggest a new explanation concerning the way antioxidants function in the living cells that can elucidate some of the conflicting data published. The aim of this study was to examine the hypothesis that the overall antioxidant capacities of cells in culture remains constant and since the cells tightly regulate this antioxidant network, supplementation with exogenous antioxidants cannot enhance the total antioxidant capacity of the cells. This assumption was examined in HaCaT, Hep3B, PC3 and Caco-2 cells using several types of antioxidant supplements. It has been shown that while the levels of the specific administrated antioxidant increased significantly intracellularly, the overall antioxidant capacity of the cells as evaluated by various methods did not increase, and in some cases, even decreased. These results support the hypothesis and demonstrate that the total antioxidant capacity of these cells in culture is kept under tight regulation and cannot be enhanced by exogenous LMWA.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Erez
authors.initials: E
authors.lastname: Koren
authors.forename: Igor
authors.initials: I
authors.lastname: Zverev
authors.forename: Isaac
authors.initials: I
authors.lastname: Ginsburg
authors.forename: Ron
authors.initials: R
authors.lastname: Kohen
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000963:Antimetabolites / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000378:metabolism; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D005290:Ferric Compounds / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism
chemical_list: D000963:Antimetabolites; D000975:Antioxidants; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D011506:Proteins; D017382:Reactive Oxygen Species; D014527:Uric Acid; D019328:Buthionine Sulfoximine; D005978:Glutathione; D001205:Ascorbic Acid; D000111:Acetylcysteine