Phosphodiesterase-5 inhibition by sildenafil citrate in a rat model of bleomycin-induced lung fibrosis

Yıldırım, Alper; Ersoy, Yasemin; Ercan, Feríha; Atukeren, Pınar; Gümüştaş, Koray; Uslu, Ünal; Ali̇can, İnci̇

doi:10.1016/j.pupt.2009.11.002

Cited by 48 publications

(39 citation statements)

References 22 publications

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“…Inghilleri and colleagues evaluated the in situ production of oxidative and nitrosative stress, and identified inflammatory cells as well as airway epithelium as the major sites of production of ROS and NO, although Inghilleri and colleagues did not elucidate the source of ROS production (22). Bleomycin-induced pulmonary hypertension is also attenuated by sildenifil, which may also be mediated by its effect on NO bioactivity through its preservation of the half-life of cyclic guanosine monophosphate (cGMP) (25). In a neonatal model of bleomycin-induced pulmonary hypertension and bronchopulmonary dysplasia, chronic treatment with inhaled NO attenuated right ventricular hypertrophy and medial wall thickness (13).…”

Section: Discussionmentioning

confidence: 99%

Lung Extracellular Superoxide Dismutase Overexpression Lessens Bleomycin-Induced Pulmonary Hypertension and Vascular Remodeling

Rheen

Fattman²,

Domarski³

et al. 2011

Am J Respir Cell Mol Biol

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Interstitial lung disease is a devastating disease in humans that can be further complicated by the development of secondary pulmonary hypertension. Accumulating evidence indicates that the oxidant superoxide can contribute to the pathogenesis of both interstitial lung disease and pulmonary hypertension. We used a model of pulmonary hypertension secondary to bleomycin-induced pulmonary fibrosis to test the hypothesis that an imbalance in extracellular superoxide and its antioxidant defense, extracellular superoxide dismutase, will promote pulmonary vascular remodeling and pulmonary hypertension. We exposed transgenic mice overexpressing lung extracellular superoxide dismutase and wild-type littermates to a single dose of intratracheal bleomycin, and evaluated the mice weekly for up to 35 days. We assessed pulmonary vascular remodeling and the expression of several genes critical to lung fibrosis, as well as pulmonary hypertension and mortality. The overexpression of extracellular superoxide dismutase protected against late remodeling within the medial, adventitial, and intimal layers of the vessel wall after the administration of bleomycin, and attenuated pulmonary hypertension at the same late time point. The overexpression of extracellular superoxide dismutase also blocked the early upregulation of two key genes in the lung known to be critical in pulmonary fibrosis and vascular remodeling, the transcription factor early growth response-1 and transforming growth factor-b. The overexpression of extracellular superoxide dismutase attenuated late pulmonary hypertension and significantly improved survival after exposure to bleomycin. These data indicate an important role for an extracellular oxidant/antioxidant imbalance in the pathogenesis of pulmonary vascular remodeling associated with secondary pulmonary hypertension attributable to bleomycin-induced lung fibrosis.

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Section: Discussionmentioning

confidence: 99%

Lung Extracellular Superoxide Dismutase Overexpression Lessens Bleomycin-Induced Pulmonary Hypertension and Vascular Remodeling

Rheen

Fattman²,

Domarski³

et al. 2011

Am J Respir Cell Mol Biol

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show abstract

“…[23,[30][31][32][33][34]46,47] Histopathological evaluations of those studies also demonstrated the positive effects of various dosages of sildenafil administration (range 2±25 mg/kg) in decreased inflammation scores.…”

mentioning

confidence: 79%

The effects of Sildenafil in liver and kidney injury in a rat model of severe scald burn: A biochemical and histopathological study

Gökakın

Atabey

Deveci

et al. 2014

Ulus Travma Acil Cerrahi Derg

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“…7 Sildenafil'in ilaç toksisitesine bağlı lipid peroksidasyonunun, nötrofil aktivasyonu ve sitokin üretimini önlediği öne sürülmüştür. 8 Ancak sildenafil'in İNH ve streptomisine bağlı toksik etkiyi önleyip önleyemediği şu ana kadar araştırıl-mamıştır.…”

Section: Gereç Ve Yöntemunclassified

Effects of sildenafil on isoniazid and streptomycin neurotoxicity in rats

Açar¹

2011

Dicle Med J

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Phosphodiesterase-5 inhibition by sildenafil citrate in a rat model of bleomycin-induced lung fibrosis

Cited by 48 publications

References 22 publications

Lung Extracellular Superoxide Dismutase Overexpression Lessens Bleomycin-Induced Pulmonary Hypertension and Vascular Remodeling

Lung Extracellular Superoxide Dismutase Overexpression Lessens Bleomycin-Induced Pulmonary Hypertension and Vascular Remodeling

The effects of Sildenafil in liver and kidney injury in a rat model of severe scald burn: A biochemical and histopathological study

Effects of sildenafil on isoniazid and streptomycin neurotoxicity in rats

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