TABLE 2.
Effects of antiviral nucleoside analogs on the activities of respiratory-chain enzyme complexesa
| Drug (concn [μM]) | Activityb
|
||||
|---|---|---|---|---|---|
| Complex I | Complex II | Complex III | Complex IV | Citrate synthase | |
| AZT (10) | 101.2 ± 14.8 | 109.8 ± 6.4 | 107.9 ± 19.6 | 85.1 ± 7.8 | ND |
| AZT (50) | 103.3 ± 14.9 | 87.5 ± 9.2 | 94.2 ± 11.2 | 71.7 ± 9.1c | 70.8 ± 10.8d |
| AMT (50) | 103.0 ± 8.5 | 96.5 ± 4.5 | 95.6 ± 24.4 | 93.7 ± 8.2 | ND |
| ddC (1) | 110.6 ± 6.6 | 112.5 ± 1.0 | 92.9 ± 20.1 | 100.9 ± 2.2 | ND |
| ddC (10) | 107.9 ± 7.6 | 104.4 ± 17.1 | 97.7 ± 9.5 | 88.2 ± 12.0 | 98.4 ± 8.9 |
| d4T (50) | 108.2 ± 15.0 | 112.3 ± 5.6 | 98.2 ± 0.6 | 113.7 ± 8.8 | ND |
HepG2 cells were exposed to various concentrations of nucleoside analogs for 6 days. Mitochondria were then extracted as described in Materials and Methods. The mean value of complex I enzyme activity was 125.3 ± 32.4 nmol/min/mg of mitochondrial protein. The mean value of complex II enzyme activity was 157.5 ± 28.9 nmol/min/mg of mitochondrial protein. Complex III activity was 0.513 ± 0.11 first-order rate constant/mg of mitochondrial protein, and complex IV activity was 0.435 ± 0.122 first-order rate constant/mg of mitochondrial protein. Citrate synthase activity was 0.378 ± 0.05 nmol/min/mg of protein.
Data are presented as percentages ± standard deviations (n ≥ 3) of the activity of the control in the same experiment. ND, not determined.
P < 0.005.
P < 0.05.