Chronic exposure to cigarette smoke causes extrapulmonary abnormalities in rats

Environ Toxicol Pharmacol. 2015 Mar;39(2):864-70. doi: 10.1016/j.etap.2015.02.016. Epub 2015 Mar 4.

Abstract

Pathophysiological features of chronic obstructive pulmonary disease (COPD) include systemic abnormalities, such as weight loss and skeletal muscle wasting. Although cigarette smoke (CS) is a major risk factor in COPD, the systemic effects of CS exposure remain to be elucidated. In this study, rats were exposed to CS or smoke-free air for 12 weeks. CS-exposed rats developed emphysema and had significantly lower body weight and food intake than control rats. The plasma ghrelin levels significantly increased with an upregulation of gastric ghrelin mRNA expression induced by CS exposure. Further, we observed low plasma insulin-like growth factor-1 levels and high tumor necrosis factor-α levels. A significant reduction of skeletal muscle strength and an increase in the mRNA expression of catabolic factors was observed in CS-exposed rats. These results indicated that chronic CS exposure induced not only pulmonary emphysema but also systemic abnormalities related to muscle catabolism associated with inflammatory responses.

Keywords: Catabolism; Chronic obstructive pulmonary disease; Cigarette smoke; Ghrelin; Rat.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Cytokines / blood
  • Eating / drug effects
  • Emphysema / blood
  • Emphysema / chemically induced*
  • Emphysema / metabolism
  • Gastric Mucosa / metabolism
  • Ghrelin / blood
  • Ghrelin / genetics
  • Lung / drug effects
  • Male
  • Muscle Proteins / genetics
  • Muscle Weakness / chemically induced
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Myostatin / genetics
  • Nicotiana / adverse effects*
  • RNA, Messenger / metabolism
  • Rats, Wistar
  • SKP Cullin F-Box Protein Ligases / genetics
  • Smoke / adverse effects*
  • Stomach / drug effects
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / genetics

Substances

  • Cytokines
  • Ghrelin
  • Mstn protein, rat
  • Muscle Proteins
  • Myostatin
  • RNA, Messenger
  • Smoke
  • Tripartite Motif Proteins
  • Fbxo32 protein, rat
  • SKP Cullin F-Box Protein Ligases
  • Trim63 protein, rat
  • Ubiquitin-Protein Ligases