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. METHODOLOGY: 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. CONCLUSION: 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.