title: Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise.
abstract: There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6. Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d. The resulting muscle injury caused increased levels of serum bleomycin-detectable iron and the amount of iron was higher in the vitamin C and NAC group. The concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), and myoglobin were significantly elevated 2, 3, and 4 d postinjury and returned to baseline levels by day 7. In addition, LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group. Levels of markers for oxidative stress (lipid hydroperoxides and 8-iso prostaglandin F2alpha; 8-Iso-PGF2alpha) and antioxidant enzyme activities were also elevated post-injury. The subjects receiving vitamin C and NAC had higher levels of lipid hydroperoxides and 8-Iso-PGF2alpha 2 d after the exercise. This acute human inflammatory model strongly suggests that vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative stress.
authors.affiliation: Biochemistry of Aging Laboratory, Center for Exercice Science, College of Human Performance, University of Florida, Gainesville, FL 32611, USA.
authors.forename: A
authors.initials: A
authors.lastname: Childs
authors.forename: C
authors.initials: C
authors.lastname: Jacobs
authors.forename: T
authors.initials: T
authors.lastname: Kaminski
authors.forename: B
authors.initials: B
authors.lastname: Halliwell
authors.forename: C
authors.initials: C
authors.lastname: Leeuwenburgh
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000975:Antioxidants / Q000032:analysis; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D001761:Bleomycin; D003402:Creatine Kinase / Q000097:blood; D015237:Dinoprost / Q000031:analogs & derivatives*; D004311:Double-Blind Method; D015444:Exercise; D028441:F2-Isoprostanes / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007501:Iron / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000293:injuries* / Q000473:pathology; D009211:Myoglobin / Q000097:blood; D009220:Myositis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D010146:Pain; D009195:Peroxidase / Q000097:blood; D010919:Placebos; D013482:Superoxide Dismutase / Q000097:blood
chemical_list: D000975:Antioxidants; D028441:F2-Isoprostanes; D015850:Interleukin-6; D008054:Lipid Peroxides; D009211:Myoglobin; D010919:Placebos; D001761:Bleomycin; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D007501:Iron; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D001205:Ascorbic Acid; D000111:Acetylcysteine