Protective Effects of Cinnamaldehyde against Mesenteric Ischemia-Reperfusion-Induced Lung and Liver Injuries in Rats.

Marwan Almoiliqy,Eskandar Qaed,Haithm Mousa,Abdulkarem Al-Sharabi,Jin Wen,Mahmoud Al-Azab,Dapeng Chen,Zhihao Liu,Li Wang,Mengqiao Lian,Yuchao Sun,Mohamed Y Zaky,Yuan Lin,Pengyuan Sun,Marco Malaguti

doi:10.1155/2020/4196548

Abstract

The aim of this study was to characterize and reveal the protective effects of cinnamaldehyde (CA) against mesenteric ischemia-reperfusion- (I/R-) induced lung and liver injuries and the related mechanisms. Sprague-Dawley (SPD) rats were pretreated for three days with 10 or 40 mg/kg/d, ig of CA, and then induced with mesenteric ischemia for 1 h and reperfusion for 2 h. The results indicated that pretreatment with 10 or 40 mg/kg of CA attenuated morphological damage in both lung and liver tissues of mesenteric I/R-injured rats. CA pretreatment significantly restored the levels of aspartate transaminase (AST) and alanine transaminase (ALT) in mesenteric I/R-injured liver tissues, indicating the improvement of hepatic function. CA also significantly attenuated the inflammation via reducing myeloperoxidase (MOP) activity and downregulating the expression of inflammation-related proteins, including interleukin-6 (IL-6), interleukin-1β (IL-1β), cyclooxygenase-2 (Cox-2), and tumor necrosis factor receptor type-2 (TNFR-2) in both lung and liver tissues of mesenteric I/R-injured rats. Pretreatment with CA significantly downregulated nuclear factor kappa B- (NF-κB-) related protein expressions (NF-κB p65, NF-κB p50, I kappa B alpha (IK-α), and inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ)) in both lung and liver tissues of mesenteric I/R-injured rats. CA also significantly downregulated the protein expression of p53 family members, including caspase-3, caspase-9, Bax, and p53, and restored Bcl-2 in both lung and liver tissues of mesenteric I/R-injured rats. CA pretreatment significantly reduced TUNEL-apoptotic cells and significantly inhibited p53 and NF-κB p65 nuclear translocation in both lung and liver tissues of mesenteric I/R-injured rats. CA neither induced pulmonary and hepatic histological alterations nor affected the parameters of inflammation and apoptosis in sham rats. We conclude that CA alleviated mesenteric I/R-induced pulmonary and hepatic injuries via attenuating apoptosis and inflammation through inhibition of NF-κB and p53 pathways in rats, suggesting the potential role of CA in remote organ ischemic injury protection.

Highlights

Mesenteric I/R injury is a serious pathological condition with characteristics of hemorrhagic shock, trauma, strangulated intestinal obstruction, and acute mesenteric ischemia (AMI) [1,2,3]
We proposed that CA pretreatment could ameliorate mesenteric I/R-induced liver and lung injuries via attenuating inflammation and apoptosis through inhibition of both NF-κB and p53 signaling pathways
The following are the pulmonary and hepatic morphological damages induced by mesenteric I/R injury in I/R rats compared with sham rats using Hematoxylin and eosin (H&E) staining: characterized with significant inflammatory cell infiltration, perivascular and interstitial edema, deposition in the alveolar spaces, and hemorrhage in lung tissues (Figure 2(a)) and nuclear condensation, cell shrinkage, and margination and apoptotic debris in liver tissues (Figure 2(b))

Summary

Introduction

Mesenteric I/R injury is a serious pathological condition with characteristics of hemorrhagic shock, trauma, strangulated intestinal obstruction, and acute mesenteric ischemia (AMI) [1,2,3]. Mesenteric I/R injury may induce remote organ injuries, including lung and liver injuries which are associated with high morbidity and mortality [4,5,6]. Mesenteric I/R-induced pulmonary injury may lead to either acute dysfunction or severe dysfunction (failure), which may further cause myocardial, hepatic, and renal failure followed by death [7,8,9]. Mesenteric I/R injury is a clinical challenge, and the effective therapeutic strategy is limited with the exception of surgery [10,11,12], showing the requirement of novel treatment options for ameliorating both direct mesenteric I/R injury and indirect remote organ injuries. Protective effects induced by natural compounds are found to ameliorate mesenteric I/R-induced local and/or remote organ injuries. Irisin protects against mesenteric I/R-induced liver injury [17]. In our previous study, CA attenuates mesenteric I/R-induced gut injury via a synergistic inhibition of p53/NF-κB signaling pathways [18]

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