Coadministration of Atorvastatin and Amiodarone Increases the Risk of Pulmonary Fibrosis in Rats

Abstract

Objective: The purpose of this study was to evaluate the effect of atorvastatin administration on amiodarone-induced pulmonary fibrosis in rats. Materials and Methods: Thirty-six male Wistar rats were randomly divided into 4 groups. The control group (CTL) received distilled water (0.3 ml intratracheally on days 0 and 2 and 0.5 ml orally from day 0 for 3 weeks). The atorvastatin group (AT), in addition to intratracheal distilled water, received 1 mg/kg of atorvastatin orally from day 0 for 3 weeks. The amiodarone group (AMI) received 2 intratracheal instillations of amiodarone (6.25 mg/kg in 0.3 ml of water) on days 0 and 2 and 0.5 ml of distilled water (like the CTL). The amiodarone plus atorvastatin group (AMI + AT) received both these drugs (same doses and methods as for the AMI and AT). After 28 days, the rate of lung fibrosis was estimated according to pathological criteria of lung sections and measurements of hydroxyproline in pieces of left lung tissue. Results: The lung hydroxyproline content was higher in the treated groups (CTL: 0.35 ± 0.017, AT: 0.38 ± 0.012, AMI: 0.375 ± 0.018 and AMI + AT: 0.38 ± 0.012 unit/mg protein), but did not reach significance when compared with the CTL (p = 0.56). Amiodarone administration significantly increased the score of pulmonary fibrosis (0.5) in comparison with the AT (0.125) and CTL (0) (p < 0.5). The combination of amiodarone and atorvastatin exacerbated the pulmonary fibrosis (1.5; p < 0.01) compared to the AMI (0.5; p < 0.001), AT (0.125) and CTL (0). Conclusion: In this study, the concomitant administration of amiodarone and atorvastatin increased pulmonary fibrosis in rats.

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