The involvement of serotonin metabolism in cigarette smoke-induced oxidative stress in rat lung in vivo.
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.
Departments of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
Way Kwok-Wai
WK
Lau
Xiang
X
Li
Dave Sze-Chun
DS
Yeung
Ka-Ho
KH
Chan
Mary Sau-Man
MS
Ip
Judith Choi-Wo
JC
Mak
D000818:Animals; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism*
D012701:Serotonin; D008995:Monoamine Oxidase; D005978:Glutathione