Some people who use AZT and other nukes develop muscle weakness. This occurs because AZT appears to damage the power plants or mitochondria (Mt) inside cells. AZT, however, is not the only drug that can damage Mt. In fact, other anti-HIV drugs, particularly other nukes, appear to have the same effect. These drugs can damage Mt in two different ways:

• First, the drugs can cause the production of highly active compounds called free radicals. These compounds damage Mt inside cells in much the same way that rust damages a car.
• Second, the drugs appear to interfere with the ability of Mt to extract energy from food.

To deal with the first problem, compounds that protect Mt from free radicals can be used. Antioxidants such as vitamins C and E, alpha-lipoic acid, Co-enzyme Q₁₀ and NAC (N-acetylcysteine) may be useful. For the second type of toxicity, B-complex vitamins, which play a role in helping to release energy from food may also be helpful. As well, B-complex vitamins, particularly vitamins B₂, B₆ and B₁₂, along with the amino acid acetylcarnitine, may help prevent the nerve damage often seen in people treated with ddC, ddI and d4T.

Doctors in Spain have found that supplements of vitamins C and E can prevent the muscle damage caused by AZT.

Study Details

Researchers conducted experiments on 23 men, some of whom had HIV infection. Some of the HIV-positive subjects received AZT at a dose of 500 mg per day. This last group of subjects later received one gram of vitamin C and 600 mg of vitamin E per day, both for one month. The researchers also performed experiments on mice, some of which also received AZT while others received AZT, vitamin C and vitamin E.

Results

The researchers found that subjects given AZT had evidence of increased production of free radicals compared with healthy, non-HIV-infected subjects. Supplements of vitamins C and E greatly suppressed production of free radicals in humans as well as mice. These antioxidants also reduced AZT-related muscle damage in mice and humans.

It would be interesting to conduct studies combining antioxidant and B-vitamin supplements with nucleoside analogues to assess their effect on conditions related to Mt damage including:

• Peripheral neuropathy
• Fatty livers
• Lactic acidosis
• Pancreatitis
• Lumps of fat on the upper body

REFERENCES

1. de la Asunción JG, del Ormo ML, Sastre J, et al. AZT treatment induces molecular and ultrastructural oxidative damage to muscle mitochondria. Journal of Clinical Investigation 1998;102(1):4-9.

2. Skuta G, Fischer GM, Janaky T, et al. Molecular mechanism of the short-term cardiotoxicity caused by 2',3'-dideoxycytidine (ddC): modulation of reactive oxygen species levels and ADP-ribosylation reactions. Biochemical Pharmacology 1999;58(12):1915-1925.

3. Masini A, Scotti C, Calligaro A, et al. Zidovudine-induced experimental myopahty: the dual mechanism of mitochondrial damage. Journal of Neurological Sciences 1999;166(2):131-140.

4. Chariot P, Drogou I, de Lacroix-Szmania I, et al. Zidovudine-induced mitochondrial disorder with massive liver steatosis, myopathy, lactic acidosis, and mitochondrial DNA depletion. Journal of Hepatology 1999;30:156-160.

5. Brinkman K, ter Hofstede HMJ, Burger DM, et al. Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as a common pathway. AIDS 1998;12:1735-1744.

6. Anonymous. Mitochondrial Myopathies. 1997:July http://www.ninds.nih.gov/patients/disorder/mitochon/mitochon.htm.

7. Garcia-Ruiz C, Colell A, Kaplowitz N and Fernandez-Checa JC. Role of oxidative stress generated from the mitochondrial electron transport chain and mitochondrial glutathione status in loss of mitochondrial function and activation of transcription factor nuclear factor-kappa B: studies with isolated mitochondria and rat hepatocytes. Molecular Pharmacology 1995;48(5):825-835.

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