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Impact of Olmesartan Medoxomil on Amiodarone-Induced Pulmonary Toxicity in Rats: Focus on Transforming Growth Factor-ß1
Basic and clinical Pharmacology and Toxicology • 2016
Publication Information
Authors
Abeer A. I. Sharaf El-Din and Omaima M. Abd Allah
Keywords
amiodarone, olmesartan medoxomil, profibrogenic cytokine, TGF-ß1, pulmonary fibrosis, rats.
Journal
Basic and clinical Pharmacology and Toxicology
Publisher
John Wiley and Sons Ltd
Volume
119
Issue
1
Pages
58- 67
publication.type
International
Paper Link
Open Link
Supplementary Materials
Not Available
Abstract
Amiodarone (AD) is one of the most frequently prescribed anti-arrhythmic agents worldwide, but its effectiveness is
limited due to the development of pulmonary toxicity. Several lines of evidence have suggested that AT1 receptor antagonists can attenuate pulmonary fibrosis in different animal models. This study was performed to evaluate the effect of olmesartan medoxomil (OM) on lung injury induced in rats by AD which was assessed biochemically (hydroxyproline content, MDA level
and SOD activity), histologically (Ashcroft criteria and Masson’s trichrome stain) and immunohistochemically (TGF-b1 expression in lung tissue). The expression levels of TGF-b1 and type I collagen mRNA were also determined by quantitative real-time
polymerase chain reaction. Forty-eight adult male rats were randomized into six equal groups: control group, OM control groups, AD group received 40 mg/kg/day, p.o. for 4 weeks to induce pulmonary injury in rats and OM-treated groups received 0.6 and 6 mg/kg/day, p.o. concomitantly with AD for the same period. The results indicated that OM significantly decreased collagen deposition and hydroxyproline content, ameliorated pathological score and decreased the elevation in type I collagen and TGFß1
mRNA expression in lung tissue. Furthermore, it attenuated the AD-induced increase in the MDA level and increased SOD activity in lung tissue. It can be concluded that OM exerts a protective effect against AD-induced lung damage in rats which is attributed to modulation of pro-fibrogenic cytokine (TGF-b1) and antioxidant effect.
limited due to the development of pulmonary toxicity. Several lines of evidence have suggested that AT1 receptor antagonists can attenuate pulmonary fibrosis in different animal models. This study was performed to evaluate the effect of olmesartan medoxomil (OM) on lung injury induced in rats by AD which was assessed biochemically (hydroxyproline content, MDA level
and SOD activity), histologically (Ashcroft criteria and Masson’s trichrome stain) and immunohistochemically (TGF-b1 expression in lung tissue). The expression levels of TGF-b1 and type I collagen mRNA were also determined by quantitative real-time
polymerase chain reaction. Forty-eight adult male rats were randomized into six equal groups: control group, OM control groups, AD group received 40 mg/kg/day, p.o. for 4 weeks to induce pulmonary injury in rats and OM-treated groups received 0.6 and 6 mg/kg/day, p.o. concomitantly with AD for the same period. The results indicated that OM significantly decreased collagen deposition and hydroxyproline content, ameliorated pathological score and decreased the elevation in type I collagen and TGFß1
mRNA expression in lung tissue. Furthermore, it attenuated the AD-induced increase in the MDA level and increased SOD activity in lung tissue. It can be concluded that OM exerts a protective effect against AD-induced lung damage in rats which is attributed to modulation of pro-fibrogenic cytokine (TGF-b1) and antioxidant effect.