Amiodarone attenuates apoptosis, but induces phospholipidosis in rat alveolar epithelial cells.
J Physiol Pharmacol
; 61(6): 671-7, 2010 Dec.
Article
in En
| MEDLINE
| ID: mdl-21224497
ABSTRACT
Amiodarone-induced pulmonary toxicity is a serious side-effect, but the underlying molecular mechanisms remain unclear. We examined phospholipidosis and apoptosis in rat alveolar epithelial cells after medium-term oral amiodarone treatment. Amiodarone (30 mg/kg daily, a dosage corresponding to that used clinically) or vehicle was administered by gavage in 33 Wistar rats for two weeks. Apoptosis was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labelling (TUNEL) and the expression of apoptosis- and phospholipidosis-related proteins was measured by immunohistochemistry. Amiodarone decreased phospholipase-C-γ1 and increased phosphatidylinositol-(4,5)-bisphosphate, resulting in phospholipidosis, evidenced by the appearance of intracellular inclusion bodies with a multi-lamellated interior. Amiodarone exerted two opposite effects on apoptosis; compared to controls, the expression of activated-caspase-8 was higher in treated rats, while the expression of apoptosis inhibitors survivin, Bcl-2 and c-Flip was lower. On the other hand, the expression of activated-caspase-3 was lower after treatment. Overall, amiodarone attenuated apoptosis, evidenced by fewer TUNEL-positive cells. Medium-term oral amiodarone administration induced phospholipidosis in rat alveolar epithelial cells. Although such treatment decreased anti-apoptotic proteins, apoptosis was attenuated via a decrease in the caspase-3 pathway. These findings improve current understanding on the mechanisms underlying amiodarone-induced pulmonary toxicity.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phospholipids
/
Pulmonary Alveoli
/
Apoptosis
/
Amiodarone
Limits:
Animals
Language:
En
Journal:
J Physiol Pharmacol
Journal subject:
FARMACOLOGIA
/
FISIOLOGIA
Year:
2010
Document type:
Article
Affiliation country:
Greece
Publication country:
PL
/
POLAND
/
POLONIA
/
POLÔNIA