J Korean Soc Emerg Med.  2003 Mar;14(1):71-77.

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

Affiliations
  • 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.

Keyword

Amiodarone; Pulmonary toxicity; Vitamin E; N-acetylcysteine

MeSH Terms

Acetylcysteine
Amiodarone
Animals
Antioxidants
Cricetinae*
Fibrosis
Hydroxyproline
Leg
Lung
Oxygen
Pulmonary Fibrosis*
Vitamin E*
Vitamins*
Acetylcysteine
Amiodarone
Antioxidants
Hydroxyproline
Oxygen
Vitamin E
Vitamins
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