Modulating the p66shc signaling pathway with protocatechuic acid protects the intestine from ischemia-reperfusion injury and alleviates secondary liver damage.
Intestinal ischemia-reperfusion (I/R) injury is a serious clinical pathophysiological process that may result in acute local intestine and remote liver injury. Protocatechuic acid (PCA), which has been widely studied as a polyphenolic compound, induces expression of antioxidative genes that combat oxidative stress and cell apoptosis. In this study, we investigated the effect of PCA pretreatment for protecting intestinal I/R-induced local intestine and remote liver injury in mice. Intestinal I/R was established by superior mesenteric artery occlusion for 45 min followed by reperfusion for 90 min. After the reperfusion period, PCA pretreatment markedly alleviated intestine and liver injury induced by intestinal I/R as indicated by histological alterations, decreases in serological damage parameters and nuclear factor-kappa B and phospho-foxo3a protein expression levels, and increases in glutathione, glutathione peroxidase, manganese superoxide dismutase protein expression, and Bcl-xL protein expression in the intestine and liver. These parameters were accompanied by PCA-induced adaptor protein p66shc suppression. These results suggest that PCA has a significant protective effect in the intestine and liver following injury induced by intestinal I/R. The protective effect of PCA may be attributed to the suppression of p66shc and the regulation of p66shc-related antioxidative and antiapoptotic factors.
Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116023, China.
Lingfei
0000-0003-3065-0525
L
Ma
Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116023, China.
Guangzhi
0000-0002-9029-3649
G
Wang
Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116023, China.
Zhao
Z
Chen
Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116023, China.
Zhenlu
Z
Li
Department of Pharmacology, Dalian Medical University, Dalian 116044, China.
Jihong
0000-0002-4221-6630
J
Yao
Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116023, China.
Haidong
H
Zhao
Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116023, China.
Shu
S
Wang
Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116023, China.
Zhenhai
0000-0002-2064-9750
Z
Ma
Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116023, China.
Hong
H
Chang
Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116023, China.
Xiaofeng
X
Tian
D000818:Animals; D062385:Hydroxybenzoates / Q000494:pharmacology / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply / Q000187:drug effects; D008107:Liver Diseases / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D055765:Shc Signaling Adaptor Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
D062385:Hydroxybenzoates; D020011:Protective Agents; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C009091:protocatechuic acid