The involvement of serotonin metabolism in cigarette smoke-induced oxidative stress in rat lung in vivo

Kwok Wai LAU, Xiang LI, Dave Sze-Chun YEUNG, Ka-Ho CHAN, Mary Sau-Man IP, Judith Choi-Wo MAK

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Abstract

Recently, we have reported the dysregulation of circulating serotonin (5-hydroxytryptamine, 5-HT) homeostasis in patients with chronic obstructive pulmonary disease (COPD). An increase in metabolism of 5-HT has been reported to induce oxidative stress via monoamine oxidase (MAO)-dependent pathway. The present study aimed at investigating the effect of cigarette smoke exposure on the systemic circulation and local airway 5-HT levels as well as MAO-mediated oxidative pathway using a cigarette smoke-exposed rat model. Male Sprague-Dawley rats (150-200 g) were exposed to either sham air or 4% (v/v, smoke/air) cigarette smoke for 1 hour daily for 56 consecutive days. Sera, bronchoalveolar larvage (BAL) and lung tissues were collected 24 hours after the last exposure. We found a significant reduction in the reduced glutathione (rGSH) and an elevation in advanced oxidation protein products (AOPP), a protein oxidation marker, in the lung of cigarette smoke-exposed group (< 0.05). A significant increase in 5-HT was found in serum (< 0.05), but not in the BAL or lung, after cigarette smoke exposure. MAO-A activity was significantly elevated in the lung of cigarette smoke-exposed group (< 0.05). Furthermore, increased superoxide anion levels were found in lung homogenates of cigarette smoke-exposed rats after incubation with 5-HT (< 0.05), which was positively associated with the increase in MAO-A activity (r = 0.639, < 0.05). Our findings supported the presence of GSH disruption and protein oxidation in the lung after cigarette smoke exposure. The metabolism of 5-HT by MAO-A in the lung enhanced cigarette smoke-induced superoxides, which might contribute to the pathogenesis of COPD. Copyright © 2012 Informa UK, Ltd.

Original languageEnglish
Pages (from-to)1413-1419
JournalFree Radical Research
Volume46
Issue number11
DOIs
Publication statusPublished - Nov 2012

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Oxidative stress
Metabolism
Smoke
Tobacco Products
Rats
Serotonin
Oxidative Stress
Lung
Monoamine Oxidase
Pulmonary diseases
Superoxides
Chronic Obstructive Pulmonary Disease
Advanced Oxidation Protein Products
Air
Oxidation
Serum
Glutathione
Sprague Dawley Rats
Proteins
Homeostasis

Citation

Lau, W. K.-W., Li, X., Yeung, D. S.-C., Chan, K.-H., Ip, M. S.-M., & Mak, J. C.-W. (2012). The involvement of serotonin metabolism in cigarette smoke-induced oxidative stress in rat lung in vivo. Free Radical Research, 46(11), 1413-1419. doi: 10.3109/10715762.2012.721928

Keywords

  • 5-hydroxytryptamine (5-HT)
  • Advanced oxidation protein products (AOPP)
  • Chronic obstructive pulmonary disease (COPD)
  • Monoamine oxidase (MAO)
  • Superoxide anion