Early Protection by Resveratrol in Rat Lung Transplantation

Abstract

BackgroundResveratrol is a multifunctional bioactive substance that has effects in anti-inflammation and prevention of ischemia-reperfusion injury. This study compared the inflammation and expression of related proteins during the early stages after transplantation to explore the effects and mechanisms of resveratrol on transplanted lung.Material/MethodsSprague-Dawley rats were randomized to receive pretreatment of resveratrol suspension (60 mg/kg; RES group), dexamethasone (1 mg/kg; DEM group), or normal saline solution (2 mL/kg; control group) 1 h before lung transplantation. The cytokine concentration in the serum and bronchoalveolar lavage fluid (BALF) of the recipients was determined 24 h after transplantation. Histopathologic evaluation, including lung injury score, and the expression of necroptosis-associated proteins was assessed.ResultsHistopathologic evaluation showed pneumocyte damage and endothelialitis associated with hemorrhage in the alveoli in the control group, the severity of which was greater than that in the other 2 groups. The levels of interleukin-6 and tumor necrosis factor-α in the serum and BALF of the RES and DEM groups were lower than those in the control group. The expression of necroptosis-associated proteins in the RES group was lower than that in the control group, and was inversely proportional to lung injury.ConclusionsPretreatment with resveratrol protected rat lung in the early stages after transplantation. We determined a relationship between necroptosis-associated proteins and transplanted lung injury, which suggests that the mechanism of lung transplantation-associated ischemia-reperfusion injury may be related to necroptosis.

Resveratrol against lung injury in an ischemia/reperfusion model of abdominal aortic rupture

“…Cell membrane injury and intracellular oxidative phosphorylation disorder caused by ROS during I/Rep lead to cell death, inflammation, and leukocyte chemotaxis. [ 19 ] The ROS lead to increased cell permeability and lysis by causing lipid peroxidation in the cell membrane. [ 16 ] As one of the end products of I/Rep injury, MDA emerges with the breakdown of polyunsaturated fatty acids.…”

“…The RES (trans-3,4,5-trihidroksistilben) is a natural polyphenolic compound with antioxidant, anti-inflammatory, and anti-fibrotic properties. [ 19 , 21 ] The antioxidant effects of RES have been investigated in various I/Rep models and tissues. However, to the best of our knowledge, there are no previous studies investigating the effects of RES on lung tissue in the I/Rep model induced by occlusion of the IAA.…”

“…In addition, the authors showed that RES reduced LIRI and improved respiratory functions by stabilizing mast cells in the lung and inhibiting NADPH oxidase. Xu et al[ 19 ] reported that RES preserved the alveolar structure in pulmonary tissue exposed to ischemia in lung transplantation models, and reduced tissue edema, necrosis, and inflammation. Another study showed that RES increased GSH and CAT levels in ischemic spinal cord tissue.…”

The role of innate immunity in the long-term outcome of lung transplantation

“…For example, Del Sorbo and colleagues suppressed apoptosis using siRNA targeting the pro-apoptotic molecule Fas, improving lung function in a mouse IRI model (58). Xu et al showed that RIPK3and MLKL-dependent necroptosis was upregulated in rat lungs undergoing IRI (59). Mingyao Liu's group showed that IRI induces necroptosis in human lung epithelial cells, and that this process could be prevented by necrostatin (inhibitor of RIPK3 mediated phosphorylation) in vitro (60); in a subsequent study, the same group showed that IRI could be prevented by administration of necrostatin in a rat orthotopic lung transplant model (61).…”

Resveratrol extracted from Chinese herbal medicines: A novel therapeutic strategy for lung diseases

“…Furthermore, resveratrol has been characterized with anti-microbial, neuroprotective, anti-aging, cardioprotective and anti-cancer activities both in vivo and in vitro ( Lee et al, 2018 , Li et al, 2018 ). Most recently, resveratrol was shown to protect rat lung in the early stages after lung transplantation ( Xu, Lv, Wang, Ye, & Hu, 2019 ). Although previous studies suggest that resveratrol or traditional Chinese prescriptions containing resveratrol has been practiced clinically to treat a variety of lung diseases, a comprehensive review with perspectives on the limitations of current pharmacology researches of resveratrol on lung diseases is still missing.…”