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

Free Radic Res. 2012 Nov;46(11):1413-9. doi: 10.3109/10715762.2012.721928. Epub 2012 Sep 10.

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 (p < 0.05). A significant increase in 5-HT was found in serum (p < 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 (p < 0.05). Furthermore, increased superoxide anion levels were found in lung homogenates of cigarette smoke-exposed rats after incubation with 5-HT (p < 0.05), which was positively associated with the increase in MAO-A activity (r = 0.639, p < 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Glutathione / metabolism
  • Immunohistochemistry
  • Lung / metabolism*
  • Lung / pathology
  • Male
  • Monoamine Oxidase / metabolism
  • Oxidative Stress / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism*
  • Smoking / adverse effects*
  • Smoking / metabolism*

Substances

  • Serotonin
  • Monoamine Oxidase
  • Glutathione