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J Korean Soc Emerg Med > Volume 14(1); 2003 > Article
Journal of The Korean Society of Emergency Medicine 2003;14(1): 71-77.
The Effect of Vitamin E and N-acetyl-cysteine in Amiodarone-induced Pulmonary Fibrosis in Hamsters
Joo Suk Oh, Kyung Ho Choi, Se Kyung Kim, Young Pil Wang, Suk Joo Rha
1Department of Emergency Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. ckyoungho@yahoo.co.kr
2Department of Thoracic and Cardiovascular Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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.
Key words: Amiodarone, Pulmonary toxicity, Vitamin E, N-acetylcysteine
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