Zidovudine-induced diaphragmatic contractile dysfunction: impact of an antioxidant diet.
OBJECTIVE
Zidovudine (AZT) is a primary drug therapy used to treat HIV-infected individuals. While AZT inhibits replication of HIV, it also induces a drug-specific myopathy resulting in altered muscle mitochondria, increased oxidative stress and muscle contractile dysfunction. The purpose of this study was to assess the impact of an antioxidant diet (high in vitamins C and E) on AZT-mediated diaphragmatic contractile dysfunction in rodents.


METHODS
Adult, Sprague-Dawley rats were assigned to feeding groups: control (CON, n = 9), AZT-treatment (AZT, n = 8), antioxidant diet only (Anti-Ox, n = 6), and AZT + antioxidant diet (AZT + Anti, n = 9). Two costal diaphragm strips were removed from each animal (under surgical anaesthesia) and evaluated for force-frequency relationship, maximal specific tension, and fatigue resistance using an in vitro preparation.


RESULTS
Results indicate significant reductions in normalized force production (20-200 Hz), including maximal specific tension, between AZT animals and all other groups. While AZT reduced diaphragm contractility, the addition of an antioxidant diet eliminated this decrease.


CONCLUSIONS
These data suggest that an increase in oxidative stress mediated by AZT may contribute to AZT-induced muscle contractile dysfunction, and that antioxidant vitamin supplementation may help ameliorate this effect.
Wheeler
Sara
S
College of Health Professions, Northern Arizona University, Flagstaff, Arizona 86011-5092, USA.
Maxwell-Bawden
Anya
A
Herb
Robert A
RA
Gallagher
Gail E
GE
Coast
J Richard
JR
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000633:toxicity; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology; D003964:Diaphragm / Q000187:drug effects* / Q000503:physiopathology; D019587:Dietary Supplements; D005260:Female; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology; D015215:Zidovudine / Q000008:administration & dosage / Q000633:toxicity*
D019380:Anti-HIV Agents; D000975:Antioxidants; D014810:Vitamin E; D015215:Zidovudine; D001205:Ascorbic Acid