The Effect of Vitamin E and N-acetyl-cysteine in Amiodarone-induced Pulmonary Fibrosis in Hamsters

ABSTRACT

PURPOSE: Amiodarone (AD) is a potent and effective anti-dysrhythmic drug, but some literature reports that it 's long-term use is associated with the development of potentially life-threatening amiodarone-induced pulmonary toxicity (AIPT). Until now, oxygen free radical theory has been the most probable hypothesis for the development of AIPT. We investigated the protective effect of two potent antioxidants, N-acetylcysteine(NAC) and vitamin E, against AIPT. METHODS: Twenty-six (26) Hamsters were divided into a sham-operation group(n=2) and the following 4 groups AD-induced effects without antioxidants (group 1, n=6), with NAC (group 2, n=6), with vitamin E (group 3, n=6), and with both NAC and vitamin E (group 4, n=6). Vitamin E (100 mg/kg) was injected intramuscularly into the hind leg once a day. At day 21, amiodarone (1.83 umol) was administered by transoral intratracheal instillation. NAC (300 mg/kg) was injected intraperitoneally just after amiodarone instillation. At day 28, amiodarone and NAC were administered again. Twenty-one (21) days after instillation of the second dose of amiodarone, the hamsters were sacrificed, and the lung fibrosis index and the hydroxyproline content were assessed. RESULTS: In the NAC-treated group (group 2), there was no significant decrease in either the lung fibrosis index, as determined by microscopic evaluation, or the lung hydrox-yproline content (p > 0.05). But there were significant decreases in the fibrosis index and the lung hydroxyproline content in the vitamin E-treated groups (group 3 and 4 ) (p < 0.05). CONCLUSION: Although vitamin E and NAC are both potent antioxidants, we found that AD-induced lung fibrosis was significantly decreased by only vitamin E and that there was no synergistic effect between vitamin E and NAC. It is possible that AIPT is developed by some other mechanisms rather than oxygen free radical injury. Vitamin E may have some other path for decreasing lung fibrosis. Further studies are warranted.