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04 January 2019 : Animal Research  

Protective Effect of Hesperidin Against Sepsis-Induced Lung Injury by Inducing the Heat-Stable Protein 70 (Hsp70)/Toll-Like Receptor 4 (TLR4)/ Myeloid Differentiation Primary Response 88 (MyD88) Pathway

Xiaoyan Yuan12ABF, Jinyuan Zhu13CD, Qi Kang2DEF, Xiaoxue He4CF, Dongfeng Guo2ACE*

DOI: 10.12659/MSM.912490

Med Sci Monit 2019; 25:107-114

Abstract

BACKGROUND: Sepsis-induced lung injury is associated with high mortality. The present investigation evaluated the protective effect of hesperidin against sepsis-induced lung injury and also postulates the possible mechanism of its action.

MATERIAL AND METHODS: Lung injury was induced by sepsis in all animals, in which sepsis was produced by cecal ligation and puncture (CLP). Animals were treated with hesperidin 10 and 20 mg/kg i.v. 30 min after the surgery. Oxygenation index and lung injury score were determined and levels of pro-inflammatory mediators and markers of oxidative stress were also estimated in the lung tissues. Moreover, expression of caspase-3, B-cell lymphoma (Bcl-2), Toll-like receptor 4 (TLR4), heat-stable protein 70 (Hsp70) and myeloid differentiation primary response 88 (MyD88) protein was estimated by Western blot assay and immunofluorescence assay.

RESULTS: Hesperidin attenuated the partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio and lung injury score in CLP-induced lung injury mice. There was a significant (p<0.01) decrease in the level of pro-inflammatory mediators in the lung tissue of CLP-induced lung injury mice. Moreover, markers of oxidative stress were attenuated in the hesperidin-treated group. Treatment with hesperidin attenuated the expression of caspase-3, Bcl-2, TLR4, Hsp70, and MyD88 protein in the lung tissue of CLP-induced lung injury mice.

CONCLUSIONS: Hesperidin protects against lung injury by attenuating the Hsp70/TLR4/MyD88 pathway in CLP-induced lung injury mice.

Keywords: Hesperidin, Lung Injury, Sepsis, Adaptor Proteins, Signal Transducing, Cecum, HSP70 Heat-Shock Proteins, Lung, Male, Myeloid Differentiation Factor 88, Signal Transduction, Toll-Like Receptor 4

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750