Chronic vitamin E deficiency promotes vitamin C deficiency in zebrafish leading to degenerative myopathy and impaired swimming behavior.

TitleChronic vitamin E deficiency promotes vitamin C deficiency in zebrafish leading to degenerative myopathy and impaired swimming behavior.
Publication TypeJournal Article
Year of Publication2013
AuthorsLebold KM, Löhr CV, Barton CL, Miller GW, Labut EM, Tanguay RL, Traber MG
JournalComparative biochemistry and physiology. Toxicology & pharmacology : CBP
Volume157
Issue4
Pagination382-9
Date Published2013 May
ISSN1532-0456
Keywordsalpha-Tocopherol, Animals, Ascorbic Acid, Ascorbic Acid Deficiency, Behavior, Animal, Fibrosis, Half-Life, Malondialdehyde, Muscle, Skeletal, Muscular Diseases, Necrosis, Oxidative Stress, Severity of Illness Index, Swimming, Vitamin E Deficiency, Zebrafish
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.

DOI10.1016/j.cbpc.2013.03.007
Alternate JournalComp. Biochem. Physiol. C Toxicol. Pharmacol.