Attenuation of bleomycin-induced lung fibrosis by oral sulfhydryl containing antioxidants in rats: erdosteine and N-acetylcysteine

Yıldırım, Zeki; Kotuk, Mahir; Iraz, Mustafa; Kuku, İrfan; Ulu, Ramazan; Armutçu, Ferah; Özen, Süleyman

doi:10.1016/j.pupt.2005.02.001

Cited by 52 publications

(42 citation statements)

References 30 publications

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“…J. Wang, Giri, Hyde, Nakashima, & Javadi, 1990), Taurin (Blaisdell & Giri, 1995;Gurujeyalakshmi, Hollinger, & Giri, 1998;Gurujeyalakshmi, Iyer, Hollinger, & Giri, 1996;Gurujeyalakshmi, Wang, & Giri, 2000;Q. J. Wang, Giri, Hyde, & Nakashima, 1989), N-Acetylcysteine (Cortijo et al, 2001;Hagiwara, Ishii, & Kitamura, 2000;Mata et al, 2003;Serrano-Mollar et al, 2003;Shahzeidi, Sarnstrand, Jeffery, McAnulty, & Laurent, 1991;Yildirim et al, 2005), Vitamin E (Kilinc et al, 1993), Curcumin (Punithavathi, Venkatesan, & Babu, 2000), Aminoguanidine (X. L. Chen, Huang, Li, Wang, & Wang, 2001; X. L. Chen, Li, Zhou, Ai, & Huang, 2003;de Rezende, Martinez, Capelozzi, Simoes, & Beppu, 2000;Giri, Biring, Nguyen, Wang, & Hyde, 2002;Hu, Xu, & Li, 1999;Yildirim et al, 2004), Melatonin (Arslan, Zerin, Vural, & Coskun, 2002;Genovese, Di Paola et al, 2005;Yildirim et al, 2006), Bilirubin (H. D. , CAPE = caffeic acid phenethyl ester , Erdosteine (Boyaci et al, 2006;Sogut et al, 2004;Yildirim et al, 2005;Yildirim et al, 2004) etc. ), Angiotensin converting enzyme inhibitors (Captopril (R. Wang, Ibarra-Sunga, Verlinski, Pick, & Uhal, 2000), Ramipril (Marshall et al, 2004) etc.…”

Section: Drug Intervention Studies In the Bleomycin Modelmentioning

confidence: 99%

“…This drug has been in clinical use as mucolytic therapy in a variety of respiratory diseases, in the management of acetaminophen overdose, and in the prevention of radiocontrast-induced nephropathy by augmenting glutathione reserves for binding of toxic metabolites. In the context of pulmonary fibrosis, is has shown effectiveness as preventive medication in the bleomycin animal model (Yildirim et al, 2005). The IFIGENIA study, a double-blind, randomized, placebo-controlled trial enrolling 182 IPF patients, tested NAC in combination with prednisone and azathioprine.…”

Section: Selected Examples Of Compounds In Clinical Trials N-acetylcymentioning

confidence: 99%

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The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?

Moeller

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Warburton

et al. 2008

The International Journal of Biochemistry & Cell Biology

841

724

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Different animal models of pulmonary fibrosis have been developed to investigate potential therapies for idiopathic pulmonary fibrosis (IPF). The most common is the bleomycin model in rodents (mouse, rat and hamster). Over the years, numerous agents have been shown to inhibit fibrosis in this model. However, to date none of these compounds are used in the clinical management of IPF and none has shown a comparable antifibrotic effect in humans. We performed a systematic review of publications on drug efficacy studies in the bleomycin model to evaluate the value of this model regarding transferability to clinical use. Between 1980 and 2006 we identified 246 experimental studies describing beneficial antifibrotic compounds in the bleomycin model. In 221 of the studies we found enough details about the timing of drug application to allow inter-study comparison. 211 of those used a preventive regimen (drug given ≤ day 7 after last bleomycin application), only 10 were therapeutic trials (> 7 days after last bleomycin application). It is critical to distinguish between drugs interfering with the inflammatory and early fibrogenic response from those preventing progression of fibrosis, the latter likely much more meaningful for clinical application. All potential antifibrotic compounds should be evaluated in the phase of established fibrosis rather than in the early period of bleomycin-induced inflammation for assessment of its antifibrotic properties. Further care should be taken in extrapolation of drugs successfully tested in the bleomycin model due to partial reversibility of bleomycin induced fibrosis over time. The use of alternative and more robust animal models, which better reflect human IPF, is warranted.

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Section: Drug Intervention Studies In the Bleomycin Modelmentioning

confidence: 99%

Section: Selected Examples Of Compounds In Clinical Trials N-acetylcymentioning

confidence: 99%

The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?

Moeller

Ask

Warburton

et al. 2008

The International Journal of Biochemistry & Cell Biology

841

724

View full text Add to dashboard Cite

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“…Investigations carried out with various antioxidant agents constitute an instance of such. (19,20) that of the SB and PB groups and comparable to that of the SS group. The picrosirius staining technique stains specifically collagen fibers.…”

Section: Discussionmentioning

confidence: 69%

Influência do biofármaco DNA-hsp65 na lesão pulmonar induzida por bleomicina

et al. 2008

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Objective: To evaluate the effects of immunization with a DNA-hsp65 vaccine in an experimental model of pulmonary fibrosis. Methods: A total of 120 male C57BL/6 mice were distributed into four groups: SS, injected with saline (placebo) and then receiving intratracheal (IT) instillation of saline; SB, injected with saline (placebo) and then receiving IT instillation of bleomycin; PB, treated with plasmid only, without bacterial genome, and then receiving IT instillation of bleomycin; and BB, treated with the vaccine and then receiving IT instillation of bleomycin. Bleomycin was instilled 15 days after the last immunization, and the animals were killed six weeks thereafter. The left and right lungs were removed, the former for morphological analysis and the latter for hydroxyproline measurements. Results: The proportion of deaths within the first 48 h after the IT instillation (deaths attributed to the surgical procedure) was higher in the SB group than in the SS group (57.7% vs. 11.1%). The mean area of pulmonary interstitial septa was greater in the SB and PB groups (53.1 ± 8.6% and 53.6 ± 9.3%, respectively) than in the SS and BB groups (32.9 ± 2.7% and 34.3 ± 6.1%, respectively). The mean area of interstitial septa stained by picrosirius was greater in the SB, PB and BB groups than in the SS group (8.2 ± 4.9%, 7.2 ± 4.2% and 6.6 ± 4.1%, respectively, vs. 2.0 ± 1.4%). The total hydroxyproline content in the lung was significantly lower in the SS group (104.9 ± 20.9 pg/lung) than in the other groups (SB: 160.4 ± 47.8 pg/lung; PB: 170.0 ± 72.0 pg/lung; and BB: 162.5 ± 39.7 pg/lung). Conclusions: Immunization with the DNA-hsp65 vaccine reduced the deposition of noncollagen matrix in a model of bleomycin-induced lung lesion.Keywords: Pulmonary fibrosis; Bleomycin; Collagen. ResumoObjetivo: Avaliar a influência do biofármaco DNA-hsp65 em um modelo de distúrbio fibrosante pulmonar experimental. Métodos: Foram estudados 120 camundongos machos C57BL/6, divididos em quatro grupos: grupo SS, animais tratados com salina (placebo) e injetados com salina intratraqueal (IT); grupo SB, tratados com salina (placebo) e injetados com bleomicina IT; grupo PB, tratados com plasmídeo, sem gene bacteriano, e injetados com bleomicina IT; e grupo BB, tratados com DNA-hsp65 e injetados com bleomicina IT. A bleomicina foi injetada 15 dias após a última imunização, e os animais sacrificados seis semanas após o uso da droga IT. O pulmão esquerdo retirado foi utilizado para análise morfológica, e o pulmão direito para dosagens de hidroxiprolina. Resultados: A proporção de camundongos que apresentaram morte não-programada depois de 48 h da injeção IT foi maior no grupo SB em comparação ao grupo SS (57,7% vs. 11,1%). A área percentual média de interstício septal foi maior nos grupos SB e PB (53,1 ± 8,6% e 53,6 ± 9,3%, respectivamente) em comparação aos grupos SS e BB (32,9 ± 2,7% e 34,3 ± 6,1%, respectivamente). Os grupos SB, PB e BB mostraram aumentos nos valores médios da área de interstício septal corada por picrosirius em compara...

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“…NAC, a glutathione precursor, is known to be an excellent source of sulfhydryl groups and is converted into metabolites that are capable of stimulating glutathione synthesis, acting directly as free radical scavengers [25][26][27][28] . It has been shown to directly reduce the level of reactive oxygen species (ROS)…”

Section: Discussionmentioning

confidence: 99%

Neuron differentiation and neuritogenesis stimulated by N-acetylcysteine (NAC)

Qian

Yang

2009

Acta Pharmacol Sin

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Aim:To investigate the effect of N-acetylcysteine (NAC), a potent antioxidant, on neuron differentiation of cultured mouse embryonic stem cells (ESCs) induced by retinoic acid (RA) in vitro. Superior cervical ganglion (SCG) neurons were used to study the effect of NAC on neuritogenesis. Methods: Immunoblotting was performed to detect the expression of microtubule-associated protein 2 (MAP2). MTT assays were used to determine cell viability. Cell death was estimated with trypan blue exclusion and Hoechst 33342 staining. Immunocytochemical analysis was carried out to identify neurons. Results: We obtained a high percentage of MAP2-positive neurons derived from embryoid bodies (EBs) induced by RA by administering 1 mmol/L NAC at differentiation day 0. On differentiation day 8, the expression of MAP2 protein was strongly upregulated in the presence of NAC. NAC promoted neuron differentiation of ES cells in a dose-and time-dependent manner. Notably, NAC suppressed cell death caused by RA during neuron differentiation. In addition, neurite extension of SCG neurons was greatly stimulated in the presence of NAC. Conclusion: These results show that NAC enhanced both neuron differentiation and neuritogenesis, suggesting that it may be used in the development of novel therapeutic approaches targeting neuron loss and neurite dystrophy in neurodegenerative diseases.

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Attenuation of bleomycin-induced lung fibrosis by oral sulfhydryl containing antioxidants in rats: erdosteine and N-acetylcysteine

Cited by 52 publications

References 30 publications

The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?

The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?

Influência do biofármaco DNA-hsp65 na lesão pulmonar induzida por bleomicina

Neuron differentiation and neuritogenesis stimulated by N-acetylcysteine (NAC)

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