The effect of melatonin on bleomycin‐induced pulmonary fibrosis in rats

Arslan, Seyfullah Oktay; Zerin, Mustafa; Vural, Hüseyín; Coşkun, Ali

doi:10.1034/j.1600-079x.2002.10796.x

Cited by 62 publications

(52 citation statements)

References 42 publications

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“…Earlier reports suggest that lung damage by BLM appears to act via the generation of ROS, which participates in DNA chain breakage (37) and lipid peroxidation of the cell membrane (38). To determine the antioxidant effect of LA on BLM-induced lung injury, we measured MDA (malondialdehyde), the GSH/GSSG ratio and T-AOC (total antioxidant capacity).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effects of α-lipoic acid on bleomycin-induced pulmonary fibrosis in rats

Liu

Ahmed²,

Nantajit³

et al. 2007

Int J Mol Med

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Abstract. Pulmonary fibrosis (PF) is a major side effect of radiotherapy and chemotherapy. Recent clinical trials, unfortunately, have failed to identify any therapeutic agent which has the potential to reduce the consequences of this devastating condition. Reactive oxygen species and tissue remodeling regulators, such as metalloproteinases (MMPs) and their inhibitors (TIMPs), are thought to be involved in the development of PF. We investigated these factors to determine the protective effects of antioxidant α-lipoic acid (LA) against antineoplastic agent bleomycin (BLM)-induced oxidant lung toxicity in Sprague-Dawley rats. At different time intervals after BLM administration, pathological changes of the lung were analyzed with the measurement of total protein in bronchoalveolar lavage fluid (BALF), hydroxyproline (HYP) content and the level of three oxidative stress markers, i.e. malondialdehyde (MDA), the GSH/GSSG ratio, and total antioxidative capability (T-AOC). Also, the expression changes of MMP-1 and TIMP-1 were measured. At day 14 or 28 after BLM administration, protein content in BALF, and HYP, MDA and T-AOC contents of the lung increased significantly with a decreased GSH/GSSG ratio, implicating an increased efflux of GSSG from the lung and consumption of GSH. In contrast, treatment with LA protected BLM-induced pulmonary injury by suppressing oxidative stress with the reduction of MDA, and the enhancement of the GSH/GSSG ratio and T-AOC. The BLM-stimulated symptoms of PF were relieved with significant reduction of HYP and total proteins in LA-treated rats. LA also ameliorated the MMP-1/TIMP-1 ratio. These results suggest that LA inhibits BLM-induced lung toxicity associated with oxidative damage. Therefore, antioxidant LA has a potential therapeutic effect in the prevention and alleviation of PF.

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Section: Discussionmentioning

confidence: 99%

Therapeutic effects of α-lipoic acid on bleomycin-induced pulmonary fibrosis in rats

Liu

Ahmed²,

Nantajit³

et al. 2007

Int J Mol Med

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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%

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

827

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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“…Additionally, melatonin ameliorated the increase in lung collagen (measured as hydroxyproline) caused by the chemotherapeutic agent. It was the judgment of the authors that, based on the outcome of their study, melatonin is a promising candidate as an agent to reduce bleomycin toxicity and prevent the associated interstitial pulmonary ® brosis (Arslan et al 2002).…”

Section: Bleomycinmentioning

confidence: 99%

Melatonin: reducing the toxicity and increasing the efficacy of drugs

Reíter¹,

Tan²,

Sainz³

et al. 2002

Journal of Pharmacy and Pharmacology

378

300

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Melatonin (N-acetyl-5-methoxytryptamine) is a molecule with a very wide phylogenetic distribution from plants to man. In vertebrates, melatonin was initially thought to be exclusively of pineal origin ; recent studies have shown, however, that melatonin synthesis may occur in a variety of cells and organs. The concentration of melatonin within body uids and subcellular compartments varies widely, with blood levels of the indole being lower than those at many other sites. Thus, when de ning what constitutes a physiological level of melatonin, it must be de ned relative to a speci c compartment. Melatonin has been shown to have a variety of functions, and research in the last decade has proven the indole to be both a direct free radical scavenger and indirect antioxidant. Because of these actions, and possibly others that remain to be de ned, melatonin has been shown to reduce the toxicity and increase the ef cacy of a large number of drugs whose side effects are well documented. Herein, we summarize the bene cial effects of melatonin when combined with the following drugs: doxorubicin, cisplatin, epirubicin, cytarabine, bleomycin, gentamicin, ciclosporin, indometacin, acetylsalicylic acid, ranitidine, omeprazole, isoniazid, iron and erythropoietin, phenobarbital, carbamazepine, haloperidol, caposide-50, morphine, cyclophosphamide and L-cysteine. While the majority of these studies were conducted using animals, a number of the investigations also used man. Considering the low toxicity of melatonin and its ability to reduce the side effects and increase the ef cacy of these drugs, its use as a combination therapy with these agents seems important and worthy of pursuit.

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The effect of melatonin on bleomycin‐induced pulmonary fibrosis in rats

Cited by 62 publications

References 42 publications

Therapeutic effects of α-lipoic acid on bleomycin-induced pulmonary fibrosis in rats

Therapeutic effects of α-lipoic acid on bleomycin-induced pulmonary fibrosis in rats

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

Melatonin: reducing the toxicity and increasing the efficacy of drugs

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