Effect of Quercetin Inhalation on Experimental Sepsis-Induced Lung Injury

Abstract

Background: Sepsis-induced lung injury is caused by recruitment of neutrophils and activated cytokines in alveoli, leading to plasma extravasation and inflammation. Quercetin was reported to have a significant anti-inflammatory activity owing to its direct inhibition of several initial processes of inflammation. This study investigated the effect of local administration of quercetin in adult SD rats with sepsisinduced lung injury. Materials and Methods: Sepsis-induced lung injury was induced by cecal ligation and puncture (CLP) in adult SD rats. Three doses of quercetin inhalation were given at 1-hr intervals in differing doses of 20, 40 and 60 mg/Kg of BW after the CLP procedure, divided into early (3 hrs after CLP) and late (6 hrs after CLP) treatment. Serum and bronchoalveolar lavage fluids (BALF) were collected after sacrifice of the animals, and neutrophils and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were analyzed by ELISA. Lung tissues were stained with hematoxylin and eosin and the severity of lung injury was evaluated under a microscope. Results: Neutrophil counts in the blood increased with the passage of time and became significant during the 9 ~ 18th hr in septic rats. However, a delayed increase in neutrophils in BALF was observed from the 12th to the 24th hr after CLP. Following treatment with quercetin inhalation, the levels of IL-1β and TNF-α in the BALF decreased significantly in both the early and late treatment groups, and early treatment with 40 mg/Kg BW showed the best efficacy. However, the abovedescribed changes in the IL-1β and TNF-α levels were not present in peripheral blood. Pathological results revealed that lung injury was less severe in the quercetin-treated groups than in the control group. Conclusions: We concluded that local administration of quercetin is effective in reducing lung injury in septic rats, especially following early treatment, with little systemic influence. It was suggested that quercetin inhalation may play a therapeutic role for the treatment of infectious lung diseases.