Abstract

Microorganisms obtained from the marine environment may represent a potential therapeutic value for multiple diseases. This study explored the possible protective role of marine-derived potential probiotic Enterococcus faecium EA9 (E. faecium) against pulmonary inflammation and oxidative stress using the cecal ligation and puncture (CLP) model of sepsis in Wistar rats. Animals were pretreated with E. faecium for 10 days before either sham or CLP surgeries. Animals were sacrificed 72 hours following the surgical intervention. The histological architecture of lung tissues was evaluated as indicated by the lung injury score. In addition, the extend of pulmonary edema was determined as wet/dry weight ratio. The inflammatory cytokines were estimated in lung tissues, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) using the enzyme-linked-immunosorbent-assay (ELISA) technique. Moreover, markers for lipid peroxidation such as thiobarbituric acid reaction substances (TBARs), and endogenous antioxidants, including reduced glutathione (GSH) were determined in lung tissues. Finally, the enzymatic activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) were assayed in the lungs. Pretreatment with E. faecium markedly attenuated CLP-induced lung injury and pulmonary edema. Markers for inflammation, including TNF-α, IL-6, and IL-1β were augmented in the lung tissues of CLP animals, while E. faecium ameliorated their augmented levels. E. faecium pretreatment also restored the elevated TBARS levels and the prohibited CAT, SOD, and GPx enzymatic activities in CLP animals. GSH levels were corrected by E. faecium in CLP animals. The inflammatory and lipid peroxidation mediators were positively correlated, while antioxidant enzymatic activities were negatively correlated with CLP-induced lung injury and pulmonary edema. Collectively, marine-derived Enterococcus faecium EA9 might be considered as a prospective therapeutic tool for the management of pulmonary dysfunction associated with sepsis.

Highlights

  • Sepsis is a life-threatening condition in which the human body responds to infection that injures the internal organs leading to their dysfunction

  • Results of the histological investigation in lung tissues showed that animals in the sham group have a normal appearance and histological features

  • Pretreatment of cecal ligation and puncture (CLP) animals with marine-derived E. faecium markedly restored the histological characteristics of lung tissues, lowered the neutrophilic inflammatory infiltration, and attenuated septal thickening and deposition of the hyaline membrane (Figure 1)

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Summary

Introduction

Sepsis is a life-threatening condition in which the human body responds to infection that injures the internal organs leading to their dysfunction. This condition might progress to septic shock. Sepsis might result in acute lung injury and acute respiratory distress (ARDS), which is a common challenge that triggers the BioMed Research International mortality rate especially in pediatric patients [3, 4]. Experimental sepsis models include the cecal ligation and puncture (CLP) model. This model is extensively used in rodents to mimic the intensive production of inflammatory mediators such as reactive oxygen species (ROS) and cytokines, which altered respiratory function resulting in pulmonary edema and inflammatory exudate accumulation [6]

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