Effect of Corticosteroids on Lung Volume-Pressure Curves in Bleomycin-Induced Lung Injury in the Rat

Grunze, M.; Parkinson, Debra; Sulavik, Stephen B.; Thrall, Roger S.

doi:10.3109/01902148809115123

Cited by 12 publications

(5 citation statements)

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“…In animal models of endotoxic shock, prophylactic treatment with dexamethasone attenuates the production of inflammatory cytokines including TNF-α and IL-1β, and prevents shock and mortality [ 24 ]. Previous studies using prolonged administration of corticosteroids, such as methylprednisolone or dexamethasone, initiated before or simultaneously with bleomycin reduced pulmonary inflammation, lung injury, and collagen deposition in this model [ 25 – 27 ].…”

Section: Discussionmentioning

confidence: 94%

Protective effect of Xuebijing injection on paraquat-induced pulmonary injury via down-regulating the expression of p38 MAPK in rats

Liu

Zhang

et al. 2014

BMC Complement Altern Med

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BackgroundExposure to paraquat results in acute lung injury. A systemic inflammatory response has been widely established as a contributor to paraquat-induced acute lung injury. Recent studies have reported that consumption of Xuebijing prevents inflammatory response-induced diseases. This study investigated whether consumption of Xuebijing protected rats against paraquat-induced acute lung injury.MethodsAdult male Sprague Dawley rats were randomly divided into four groups: control group; paraquat group; paraquat + Xuebijing group; and paraquat + dexamethasone group. Rats in the paraquat, paraquat + Xuebijing and paraquat + dexamethasone groups were intraperitoneally injected with paraquat (30 mg/kg) or administered paraquat and Xuebijing at 8 mL/kg or dexamethasone at 5 mg/kg, respectively, via an injection into the tail vein. Lung p38 MAPK, NF-κB65, IkB, p-IκB-α, HIF-1α, Nrf2 and TGF-β1 expression were essayed using western blotting. IL-6, TNF-α, IL-1β, IL-10, TGF-β1 and PIIIP were measured using ELISA. ROS, oxidised glutathione and glutathione activity were measured.ResultsAfter inducing acute lung injury with paraquat for 24 h, Xuebijing was observed to block lung p-p38 MAPK, NF-κB65, HIF-1α, p-IκB-α and TGF-β1 expression, and increased Nrf2 and IkB expression. The numbers of neutrophils and lymphocytes and total number of cells were significantly lower in the Xuebijing group compared with the control group. IL-6, TNF-α, IL-1β, TGF-β1 and PIIIP levels were significantly decreased in the Xuebijing group. ROS and oxidised glutathione activity were markedly inhibited by Xuebijing. Histological evaluation showed attenuation of the effects of Xuebijing on paraquat-induced lung injury. Compared with the paraquat + dexamethasone group, the Xuebijing + paraquat group showed no significant differences.ConclusionsInhibiting the expression of p38 MAPK and NF-κB65 was crucial for the protective effects of Xuebijing on paraquat-induced acute lung injury. The findings suggest that Xuebijing could effectively ameliorate paraquat-induced acute lung injury in rats. Xuebijing was as effective as dexamethasone at improving paraquat-induced lung injury by regulating lung inflammation, lung function and oxidative stress responses.

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Section: Discussionmentioning

confidence: 94%

Protective effect of Xuebijing injection on paraquat-induced pulmonary injury via down-regulating the expression of p38 MAPK in rats

Liu

Zhang

et al. 2014

BMC Complement Altern Med

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“…[21][22][23] Although an important finding, its clinical relevance is questionable as anti-inflammatory treatment is always given after lung damage has occurred. In our study the corticosteroid concentration used was much lower than in previous studies, 21-23 treatment was initiated after bleomycin induced lung injury, and it was only administered for a short time.…”

Section: Discussionmentioning

confidence: 99%

“…19 20 Previous studies using prolonged administration of corticosteroids such as methylprednisolone or dexamethasone initiated before or simultaneously with bleomycin reduced pulmonary inflammation, lung injury, and collagen deposition in this model. [21][22][23] However, as anti-inflammatory treatment usually starts after lung injury has occurred, the clinical relevance of starting treatment in animals before or at the time of injury is questionable.…”

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confidence: 99%

Short course dexamethasone treatment following injury inhibits bleomycin induced fibrosis in rats

Dik

McAnulty²,

Versnel³

et al. 2003

Thorax

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Background: Corticosteroids are routinely used in patients with pulmonary fibrosis. The timing for initiation of treatment is likely to be crucial for corticosteroids to exert an antifibrotic effect. Experimental studies in animals have examined the effect of corticosteroid treatment starting before or at the time of lung injury. However, this is not representative of the human condition as treatment only begins after disease has been established. We examined the effect of a short course corticosteroid treatment starting 3 days after bleomycin induced lung injury on the development of pulmonary fibrosis. Methods: Bleomycin (1.5 mg/kg) was instilled intratracheally into rats to induce pulmonary fibrosis. The effect of a 3-day course of dexamethasone (0.5 mg/kg) initiated 3 days after bleomycin induced lung injury on cell proliferation and collagen deposition was examined by analysing bronchoalveolar lavage (BAL) fluid and lung tissue. Results: Treating bleomycin exposed animals after injury with dexamethasone for 3 days inhibited lung collagen deposition compared with animals exposed to bleomycin without dexamethasone treatment (15.2 (2.2) mg collagen/lung v 22.5 (2.1) mg/lung; p<0.05). Dexamethasone treatment reduced pulmonary parenchymal cell proliferation in bleomycin exposed rats but did not influence BAL fluid mitogenic activity for lung fibroblasts or alter the BAL fluid levels of the fibrogenic mediators transforming growth factor-β 1 , platelet derived growth factor-AB, and thrombin. Conclusions: A 3 day course of dexamethasone treatment initiated 3 days after bleomycin induced lung injury reduces lung cell proliferation and collagen deposition by mechanisms other than through reduction of transforming growth factor-β 1 , platelet derived growth factor-AB, and thrombin levels in BAL fluid. We propose that an early short course treatment with dexamethasone may be useful in inhibiting pulmonary fibrosis.

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“…The initial studies in animal models (mostly conducted in the rat) showed that glucocorticoids clearly reduced bleomycin-induced pulmonary fibrosis by reducing collagen synthesis and deposition (Phan et al 1981;Sterling et al 1982). Later studies suggested that decreased inflammatory cell infiltration (Grunze et al 1988), decreased parenchymal cell proliferation (Dik et al 2003b), and increased parenchymal inflammatory cell apoptosis ) might also contribute to the antifibrotic effects of glucocorticoids. However, these findings have not been universally confirmed.…”

Section: Figmentioning

confidence: 97%

Resistance of fibrogenic responses to glucocorticoid and 2-methoxyestradiol in bleomycin-induced lung fibrosis in miceThis article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.

Langenbach

Wheaton

Fernandes

et al. 2007

Can. J. Physiol. Pharmacol.

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Bleomycin-induced lung fibrosis in mice reproduces some key features of pulmonary fibrosis in humans including alveolar inflammation, myofibroblast proliferation, and collagen deposition. Glucocorticoids have been used as first-line therapy for the treatment of lung fibrosis, although their clinical efficacy is equivocal. We examined the effect of the glucocorticoid, methylprednisolone (MP), and the estrogen metabolite, 2-methoxyestradiol (2MEO) on bleomycin-induced bronchoalveolar inflammation, fibrosis, and changes in lung function. The characterization of the time-course of the bleomycin-induced fibrosis indicated that lung dry mass and hydroxyproline content showed less variance than histopathological assessment of fibrosis. The bleomycin-induced increases in bronchoalveolar lavage (BAL) fluid cell number and protein levels were not significantly influenced by treatment with either MP (1 mg.(kg body mass)(-1).day(-1), i.p.) or 2MEO (50 mg.(kg body mass)(-1).day(-1), i.p.). Lung fibrosis, measured histopathologically or by hydroxyproline content, was not significantly influenced by either MP or 2MEO treatment, whereas the latter agent did reduce the increment in lung dry mass. The enlargement of alveolar airspaces and the decline in lung compliance were exacerbated by MP treatment. These data suggest that bleomycin-induced pulmonary fibrosis is resistant to inhibition by concurrent treatment with either glucocorticoids or 2MEO.

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Effect of Corticosteroids on Lung Volume-Pressure Curves in Bleomycin-Induced Lung Injury in the Rat

Cited by 12 publications

References 12 publications

Protective effect of Xuebijing injection on paraquat-induced pulmonary injury via down-regulating the expression of p38 MAPK in rats

Protective effect of Xuebijing injection on paraquat-induced pulmonary injury via down-regulating the expression of p38 MAPK in rats

Short course dexamethasone treatment following injury inhibits bleomycin induced fibrosis in rats

Resistance of fibrogenic responses to glucocorticoid and 2-methoxyestradiol in bleomycin-induced lung fibrosis in miceThis article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.

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