Effect of zidovudine (AZT) on the structure and function of rat skeletal muscle

Abstract

The role of the anti-HIV agent zidovudine (ZDV = AZT) in the generation of mitochondrial myopathies and subsequent skeletal muscle contractile deficiencies was evaluated in male rats given ZDV in drinking water (1 mg/mL). After 6 weeks, there was no difference in treadmill run time between experimental (n = 6) and control (n = 6) rats. ZDV did not affect tension output by the gastrocnemius-plantaris-soleus muscle group when stimulated in situ at frequencies of 15, 30, 45, and 75 tetani/min, nor did the drug affect the cytochrome oxidase activity of fast glycolytic, fast oxidative glycolytic, or slow oxidative fiber types after 6 or 15 weeks of treatment. A group of female rats, similarly evaluated after 6 weeks of ZDV at 1 (n = 4) or 2 (n = 4) mg/mL, also did not display any discernable deficiencies. However, when the data from all 10 control rats were compared with those of the 19 ZDV rats, the cytochrome oxidase activity of fast oxidative glycolytic muscle of the ZDV rats was significantly higher (35.0 +/- 1.36 versus 40.7 +/- 1.14 mumol.min-1.g-1; p < 0.05). No ultrastructural abnormalities were observed in 15-week ZDV-treated cardiac muscle or in any of the three skeletal muscle fiber types. These results suggest that ZDV-related myopathies observed in AIDS patients may be due to interactions between the drug and complications associated with HIV infection.

Zidovudine (AZT) induced alterations in mitochondrial biogenesis in rat striated muscles

“…AZT and ddI intakes were approximately 108 mg·kg -1 ·day -1 , which was similar to those reported in previous studies in which AZT was dissolved in drinking water (Engbretson 1996;Lewis et al 1992). …”

“…1B). The result of this subset of animals is similar to that previously reported (Engbretson 1996). Thus, the performance deficit observed was likely due to the inability of most of the AZT-treated animals to maintain blood pressure, rather than to a decrement in mitochondrial enzyme activity.…”

“…Thus, our results obtained after the 28-day treatment period may represent one of the earliest in vivo manifestations of AZT-induced mitochondrial dysfunction. While the dose administered in this and other (Engbretson 1996;Lewis et al 1992) studies ranges from approximately 2-to 10-fold that used clinically (Lamperth et al 1991;Lewis et al 1992), the present results suggest that AZT alone has the potential to reduce endurance performance in patients using the drug.…”

“…They were given food and water ad libitum. For the treated animals, both AZT (n = 14) and ddI (n = 11) were administered in the drinking water at a concentration of 1 mg·mL -1 for 28 days (Lewis et al 1992;Engbretson 1996). To ensure that the presence of the drug did not alter the water intake, water consumption of the animals was monitored daily, and is reported as cumulative water consumption over the entire treatment period (Table 1).…”