title: Treatment of acute paraquat intoxication using recommended megadose of vitamin C: a reappraisal.
abstract: Megadose of vitamin C (MVC) has been proposed for an emergent treatment of acute paraquat (PQ) poisoning. However, the safety issue of this treatment protocol has not been evaluated. Here, we present the first evidence that vitamin C can promote aggravated production of hydroxyl radical (OH(•)) via interacting with preexisting PQ(+•)/H2O2 system in a nonmetal-catalyzed manner. This enhanced oxidative stress would therefore expect to cause more deleterious effect during acute PQ intoxication. To lend support to this possibility, we set out to attest the effects of MVC on a simulated, PQ-intoxicated, Madin-Darby canine kidney (MDCK) cell model. First, PQ alone could trigger oxidative-nitrosative stress (ONS) through robust generation of reactive oxygen species and nitric oxide (NO) that could induce apoptotic killing via promoting effective release of mitochondrial cytochrome c, an apoptogenic factor. The percentage of apoptosis for MDCK cells treated with 1.0 mM PQ for 24 h was 16.3 ± 13.0%. However, when MDCK cells were treated with a combination of PQ (1.0 mM) and MVC (20 mM) for 24 h, the severity of apoptotic killing was further exacerbated as reflected by a nearly 7-fold increase in the release of mitochondrial cytochrome c and the percentage of apoptotic cell population rose sharply to 90.7 ± 5.1%. These data indicate that MVC apparently exacerbates further killing rather than cytoprotection on this simulated, PQ-intoxicated MDCK cell model and suggest that the treatment of PQ poisoning using MVC protocol should be cautious.
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center , Taipei , Taiwan.
authors.forename: J-B
authors.initials: JB
authors.lastname: Chang
authors.forename: C-C
authors.initials: CC
authors.lastname: Lin
authors.forename: J-F
authors.initials: JF
authors.lastname: Chiou
authors.forename: S-Y
authors.initials: SY
authors.lastname: Mau
authors.forename: T-Z
authors.initials: TZ
authors.lastname: Liu
authors.forename: C-H
authors.initials: CH
authors.lastname: Chen
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000009:adverse effects*; D002478:Cells, Cultured; D004285:Dogs; D004357:Drug Synergism; D006861:Hydrogen Peroxide / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D018613:Microscopy, Confocal; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010269:Paraquat / Q000506:poisoning*; D011041:Poisoning / Q000188:drug therapy / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D010269:Paraquat; D001205:Ascorbic Acid