Effects of intratracheal administration of bleomycin on GSH-shuttle enzymes, catalase, lipid peroxidation, and collagen content in the lungs of hamsters

Giri, Shri N.; Zhang-liu, Chen; Younker, Wanda R.; Schiedt, Mary J.

doi:10.1016/0041-008x(83)90052-2

Cited by 78 publications

(27 citation statements)

References 27 publications

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“…This is consistent with findings by other investigators who identified ROS as pivotal players in BLM-induced lung fibrosis. Increased levels of thiobarbituric acid reaction products were found in lung tissue of hamsters upon intratracheal administration of BLM (35), indicating increased amounts of lipid peroxides. Increased ROS production has also been detected in lung phagocytes and type II alveolar epithelial cells in BLM-induced lung fibrosis in the rat (36).…”

Section: Discussionmentioning

confidence: 95%

α‐melanocyte–stimulating hormone suppresses bleomycin‐induced collagen synthesis and reduces tissue fibrosis in a mouse model of scleroderma: Melanocortin peptides as a novel treatment strategy for scleroderma?

Kokot¹,

Sindrilaru²,

Sunderkötter³

et al. 2009

Arthritis & Rheumatism

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HO-1). In the BLM mouse model, ␣-MSH reduced skin fibrosis and collagen content and increased tissue levels of SOD2 and HO-1. In skin and HDFs from patients with SSc, both MC-1R and POMC messenger RNAs were detected, but there were no differences compared with healthy controls.Conclusion. Alpha-melanocyte-stimulating hormone and related peptides that exert their effects via MC-1R may provide a novel antifibrogenic therapeutic tool for the treatment of fibrotic diseases such as scleroderma.Fibrotic diseases are a major challenge in medicine with regard to both pathogenesis and therapeutic intervention. The clinical spectrum of such disorders comprises many organs and includes localized and systemic scleroderma (SSc), idiopathic pulmonary fibrosis, Presented by Dr. Kokot in partial fulfillment of the requirements for a PhD degree,

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Section: Discussionmentioning

confidence: 95%

α‐melanocyte–stimulating hormone suppresses bleomycin‐induced collagen synthesis and reduces tissue fibrosis in a mouse model of scleroderma: Melanocortin peptides as a novel treatment strategy for scleroderma?

Kokot¹,

Sindrilaru²,

Sunderkötter³

et al. 2009

Arthritis & Rheumatism

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“…For many years, there has been controversy regarding the primary role of these enzymes. While several authors supported the notion that these enzymes play a major role in the protection against oxidative damage under normal physiological conditions (18 -20), others believed in a protective role for these enzymes only in situations of oxidative stress (21)(22)(23). Recent studies using knockout mice as a model have provided unexpected data about the function of the most abundant glutathione peroxidase, Gpx1.…”

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confidence: 99%

Mice with a Homozygous Null Mutation for the Most Abundant Glutathione Peroxidase, Gpx1, Show Increased Susceptibility to the Oxidative Stress-inducing Agents Paraquat and Hydrogen Peroxide

Haan

Bladier

Griffiths

et al. 1998

Journal of Biological Chemistry

406

267

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Glutathione peroxidases have been thought to function in cellular antioxidant defense. However, some recent studies on Gpx1 knockout (؊/؊) mice have failed to show a role for Gpx1 under conditions of oxidative stress such as hyperbaric oxygen and the exposure of eye lenses to high levels of H 2 O 2 . These findings have, unexpectedly, raised the issue of the role of Gpx1, especially under conditions of oxidative stress. Here we demonstrate a role for Gpx1 in protection against oxidative stress by showing that Gpx1 (؊/؊) mice are highly sensitive to the oxidant paraquat. Lethality was already detected within 24 h in mice exposed to paraquat at 10 mg⅐kg ؊1 (approximately 1 ⁄7 the LD 50 of wild-type controls). The effects of paraquat were dose-related. In the 30 mg⅐kg ؊1 -treated group, 100% of mice died within 5 h, whereas the controls showed no evidence of toxicity. We further demonstrate that paraquat transcriptionally upregulates Gpx1 in normal cells, reinforcing a role for Gpx1 in protection against paraquat toxicity. Finally, we show that cortical neurons from Gpx1 (؊/؊) mice are more susceptible to H 2 O 2 ; 30% of neurons from Gpx1 (؊/؊) mice were killed when exposed to 65 M H 2 O 2 , whereas the wild-type controls were unaffected. These data establish a function for Gpx1 in protection against some oxidative stressors and in protection of neurons against H 2 O 2 . Further, they emphasize the need to elucidate the role of Gpx1 in protection against different oxidative stressors and in different disease states and suggest that Gpx1 (؊/؊) mice may be valuable for studying the role of H 2 O 2 in neurodegenerative disorders.

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“…in the VS and QS groups can be explained by the consumption of reduced GSH during the activation of antioxidant mechanisms in response to bleomycin injury, as previously reported. (21) Since the mean reduced GSH values were comparable in the VB and QB groups, we can propose that the beneficial effects of quercetin in the present model of pulmonary inflammation did not involve the GSH-dependent antioxidant system. In vitro studies of enzymatic and nonenzymatic lipid peroxidation of murine hepatic membranes support this hypothesis.…”

Section: Discussionmentioning

confidence: 96%

“…Once established, the resulting interstitial pneumonia bears more resemblance to fibrotic non-specific interstitial pneumonia than to human idiopathic pulmonary fibrosis or acute lung injury. (20)(21)(22) presented significant histological changes, predominantly in a peribronchial distribution. Large areas of mixed cellular infiltrates, consisting predominantly of neutrophils were seen, accompanied by evidence of type II pneumocyte proliferation and a few hyaline membranes.…”

Section: Discussionmentioning

confidence: 99%

Efeitos da quercetina na lesão pulmonar induzida por bleomicina: um estudo preliminar

et al. 2008

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Objective: To investigate the effects of quercetin in a model of bleomycin-induced pulmonary inflammation and fibrosis. Methods: Seventynine adult male hamsters were randomized to receive intratracheal (IT) instillations and intraperitoneal (IP) injections in four configurations: IP vehicle/IT saline (VS group, n = 16); IP quercetin/IT saline (QS group, n = 16); IP vehicle/IT bleomycin (VB group, n = 27); and IP quercetin/ IT bleomycin (QB group, n = 20). Quercetin and bleomycin were administered at 30 mg/kg/day and 10 U/kg, respectively. Quercetin was started/discontinued 3 days before/14 days after the IT instillations. Results: The mortality rate was significantly higher in the VB group than in the other groups (44% vs. VS: 0%; QS: 0%; and QB: 15%). Lung levels of thiobarbituric acid reactive substances (× 10 −2 nmol/mg) were significantly higher in the VB group (6.6 ± 1.3 vs. VS: 5.5 ± 0.8; QS: 2.5 ± 0.6; and QB: 5.8 ± 0.6). Lung levels of reduced glutathione (× 10 −2 nmol/mg) were significantly lower in the VB/QB groups than in the VS/QS groups (28.9 ± 13.8/28.6 ± 14.8 vs. 43.9 ± 16.0/51.1 ± 20.3), whereas those of hydroxyproline (mg/g) were significantly higher (201.6 ± 37.3/177.6 ± 20.3 vs. 109.6 ± 26.1/117.5 ± 32.0).Mean lung septal thickness (µm) was greatest in the VB group (16.9 ± 3.2 vs. VS: 3.0 ± 0.3; QS: 3.3 ± 0.2; and QB: 5.2 ± 1.1). Conclusions: In a hamster model of lung injury, quercetin exhibited anti-inflammatory effects that are related, at least in part, to its antioxidant properties.Keywords: Pulmonary fibrosis; Bleomycin; Flavonoids; Lipid peroxidation. ResumoObjetivo: Investigar os efeitos da quercetina em um modelo de inflamação pulmonar e fibrose induzidas por bleomicina. Métodos: Setenta e nove hamsters machos adultos foram randomizados para aplicação de injeções pelas vias intratraqueal (IT) e intraperitoneal (IP) em quatro configurações: veículo IP/salina IT (grupo VS, n = 16); salina IT/quercetina IP (grupo QS, n = 16); bleomicina IT/veículo IP (grupo VB, n = 27); e bleomicina IT/quercetina IP (grupo QB, n = 20). A quercetina e a bleomicina foram aplicadas em doses de 30 mg/kg/dia e 10 U/kg, respectivamente. A quercetina foi iniciada/suspensa 3 dias antes/14 dia depois das injeções IT. Resultados: A taxa de mortalidade do grupo VB foi significantemente superior à dos demais grupos (44% vs. VS: 0%; QS: 0%; QB: 15%). O grupo VB exibiu níveis pulmonares de substâncias reativas ao ácido tiobarbitúrico (× 10 −2 nmol/mg) significativamente maiores (6,6 ± 1,3 vs. VS: 5,5 ± 0,8; QS: 2,5 ± 0,6; e QB: 5,8 ± 0,6). Os grupos VB/QB mostraram níveis pulmonares de glutationa reduzida (× 10 −2 nmol/mg) significativamente menores que os dos grupos VS/QS (28,9 ± 13,8/28,6 ± 14,8 vs. 43,9 ± 16,0/51,1 ± 20,3) e níveis de hidroxiprolina (mg/g) significativamente maiores (201,6 ± 37,3/177,6 ± 20,3 vs. 109,6 ± 26,1/117,5 ± 32,0). A espessura média do septo alveolar (µm) do grupo VB foi a maior (16,9 ± 3,2 vs. VS: 3,0 ± 0,3; QS: 3,3 ±0,2; e QB: 5,2 ± 1,1). Conclusões: Em um modelo animal de lesã...

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Effects of intratracheal administration of bleomycin on GSH-shuttle enzymes, catalase, lipid peroxidation, and collagen content in the lungs of hamsters

Cited by 78 publications

References 27 publications

α‐melanocyte–stimulating hormone suppresses bleomycin‐induced collagen synthesis and reduces tissue fibrosis in a mouse model of scleroderma: Melanocortin peptides as a novel treatment strategy for scleroderma?

α‐melanocyte–stimulating hormone suppresses bleomycin‐induced collagen synthesis and reduces tissue fibrosis in a mouse model of scleroderma: Melanocortin peptides as a novel treatment strategy for scleroderma?

Mice with a Homozygous Null Mutation for the Most Abundant Glutathione Peroxidase, Gpx1, Show Increased Susceptibility to the Oxidative Stress-inducing Agents Paraquat and Hydrogen Peroxide

Efeitos da quercetina na lesão pulmonar induzida por bleomicina: um estudo preliminar

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