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: Katie M Lebold, Christiane V Löhr, Carrie L Barton, Galen W Miller, Edwin M Labut, Robert L Tanguay, Maret G Traber
• Journal: Comparative biochemistry and physiology. Toxicology & pharmacology : CBP (Comp Biochem Physiol C Toxicol Pharmacol) Vol. 157 Issue 4 Pg. 382-9 (May 2013) ISSN: 1532-0456 [Print] United States
• PMID: 23570751 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Malondialdehyde
• alpha-Tocopherol
• Ascorbic Acid

Topics

• Animals
• Ascorbic Acid (administration & dosage, analysis, metabolism)
• Ascorbic Acid Deficiency (etiology)
• Behavior, Animal (physiology)
• Fibrosis (pathology)
• Half-Life
• Malondialdehyde (metabolism)
• Muscle, Skeletal (metabolism, pathology)
• Muscular Diseases (etiology)
• Necrosis (pathology)
• Oxidative Stress
• Severity of Illness Index
• Swimming
• Vitamin E Deficiency (complications)
• Zebrafish (metabolism, physiology)
• alpha-Tocopherol (metabolism)