Exercise preconditioning and resveratrol reduce the susceptibility of rats with obstructive jaundice to endotoxin and alleviate lung injury

Front Immunol. 2024 Dec 18:15:1466615. doi: 10.3389/fimmu.2024.1466615. eCollection 2024.

Abstract

Introduction: Endotoxemia is a common issue for patients with biliary obstruction. The lung is the most affected organ by endotoxins. Exercise training can alleviate lipopolysaccharide (LPS)-induced lung inflammation and resveratrol has biological effects similar to exercise. In this study, we evaluated the protective effects of exercise preconditioning, resveratrol, and their combination on LPS-induced lung injury and mortality in rats with obstructive jaundice.

Methods: Endotoxemia was simulated in rats by common bile duct ligation (CBDL) and intraperitoneal injection of low-dose LPS. The treatment groups were pretreated with exercise and/or resveratrol to assess their effects on lung injury and mortality. Immunohistochemistry, immunofluorescence, and ELISA were subsequently used to evaluate the impact of exercise and/or resveratrol on inflammation in lung tissue and bronchoalveolar lavage fluid.

Results: We found that even in the early stages, compared to sham-LPS rats, low-dose LPS induced excessive systemic inflammatory responses in CBDL rats, as evidenced by a significant increase in TNF-α and IL-6, severe lung inflammation, lung injury, and higher mortality rates, indicating that cholestasis increased rats' susceptibility to endotoxins. Exercise training reduced neutrophil infiltration in the lungs of model rats and IL-6 levels in bronchoalveolar lavage fluid. Both exercise training and resveratrol exhibited synergistic effects in reducing macrophage accumulation in lung tissues, lowering TNF-α and IL-6 levels in the lungs, and decreasing TNF-α concentration in bronchoalveolar lavage fluid. Additionally, exercise and combined interventions both significantly increased the expression of IL-10. The interventions induced a marked improvement in lung tissue pathological damage and lung edema in model rats and prolonged the survival time of rats with obstructive jaundice.

Discussion: This study demonstrates that exercise preconditioning and/or resveratrol can significantly reduce rats' susceptibility to endotoxins after CBDL and alleviate lung injuries through their anti-inflammatory effects, thereby decreasing the mortality risk.

Keywords: endotoxemia; exercise; inflammation; lung injury; obstructive jaundice; resveratrol.

MeSH terms

  • Acute Lung Injury / etiology
  • Acute Lung Injury / immunology
  • Acute Lung Injury / prevention & control
  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Disease Models, Animal
  • Disease Susceptibility
  • Endotoxemia / immunology
  • Endotoxemia / therapy
  • Endotoxins
  • Jaundice, Obstructive* / drug therapy
  • Jaundice, Obstructive* / immunology
  • Jaundice, Obstructive* / therapy
  • Lipopolysaccharides*
  • Lung / drug effects
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Lung Injury / etiology
  • Lung Injury / prevention & control
  • Male
  • Physical Conditioning, Animal*
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol* / administration & dosage
  • Resveratrol* / pharmacology
  • Resveratrol* / therapeutic use

Substances

  • Resveratrol
  • Lipopolysaccharides
  • Endotoxins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by Natural Science Foundation of Shanxi Province (No. 201801D121362).