title: Chronic vitamin E deficiency promotes vitamin C deficiency in zebrafish leading to degenerative myopathy and impaired swimming behavior.
abstract: We hypothesized that zebrafish (Danio rerio) undergoing long-term vitamin E deficiency with marginal vitamin C status would develop myopathy resulting in impaired swimming. Zebrafish were fed for 1 y a defined diet without (E-) and with (E+) vitamin E (500 mg α-tocopherol/kg diet). For the last 150 days, dietary ascorbic acid concentrations were decreased from 3500 to 50 mg/kg diet and the fish sampled periodically to assess ascorbic acid concentrations. The ascorbic acid depletion curves were faster in the E- compared with E+ fish (P < 0.0001); the estimated half-life of depletion in the E- fish was 34 days, while in it was 55 days in the E+ fish. To assess swimming behavior, zebrafish were monitored individually following a "startle-response" stimulus, using computer and video technology. Muscle histopathology was assessed using hematoxylin and eosin staining on paramedian sections of fixed zebrafish. At study end, E- fish contained 300-fold less α-tocopherol (p < 0.0001), half the ascorbic acid (p = 0.0001) and 3-fold more malondialdehyde (p = 0.0005) than did E+ fish. During the first minute following a tap stimulus (p < 0.05), E+ fish swam twice as far as did E- fish. In the E- fish, the sluggish behavior was associated with a multifocal, polyphasic, degenerative myopathy of the skeletal muscle. The myopathy severity ranged from scattered acute necrosis to widespread fibrosis and was accompanied by increased anti-hydroxynonenal staining. Thus, vitamin E deficiency in zebrafish causes increased oxidative stress and a secondary depletion of ascorbic acid, resulting in severe damage to muscle tissue and impaired muscle function.
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Katie M
authors.initials: KM
authors.lastname: Lebold
authors.forename: Christiane V
authors.initials: CV
authors.lastname: Löhr
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Barton
authors.forename: Galen W
authors.initials: GW
authors.lastname: Miller
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Labut
authors.forename: Robert L
authors.initials: RL
authors.lastname: Tanguay
authors.forename: Maret G
authors.initials: MG
authors.lastname: Traber
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism; D001206:Ascorbic Acid Deficiency / Q000209:etiology*; D001522:Behavior, Animal / Q000502:physiology*; D005355:Fibrosis / Q000473:pathology; D006207:Half-Life; D008315:Malondialdehyde / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000209:etiology*; D009336:Necrosis / Q000473:pathology; D018384:Oxidative Stress; D012720:Severity of Illness Index; D013550:Swimming; D014811:Vitamin E Deficiency / Q000150:complications*; D015027:Zebrafish / Q000378:metabolism* / Q000502:physiology; D024502:alpha-Tocopherol / Q000378:metabolism
chemical_list: D008315:Malondialdehyde; D024502:alpha-Tocopherol; D001205:Ascorbic Acid