I-FABP as Biomarker for the Early Diagnosis of Acute Mesenteric Ischemia and Resultant Lung Injury

Abstract

Acute mesenteric ischemia (AMI) is a life-threatening condition that can result in multiple organ injury and death. A timely diagnosis and treatment would have a significant impact on the morbidity and mortality in high-risk patient population. The purpose of this study was to investigate if intestinal fatty acid binding protein (I-FABP) and α-defensins can be used as biomarkers for early AMI and resultant lung injury. C57BL/6 mice were subjected to intestinal ischemia by occlusion of the superior mesenteric artery. A time course of intestinal ischemia from 0.5 to 3 h was performed and followed by reperfusion for 2 h. Additional mice were treated with N-acetyl-cysteine (NAC) at 300 mg/kg given intraperitoneally prior to reperfusion. AMI resulted in severe intestinal injury characterized by neutrophil infiltrate, myeloperoxidase (MPO) levels, cytokine/chemokine levels, and tissue histopathology. Pathologic signs of ischemia were evident at 1 h, and by 3 h of ischemia, the full thickness of the intestine mucosa had areas of coagulative necrosis. It was noted that the levels of α-defensins in intestinal tissue peaked at 1 h and I-FABP in plasma peaked at 3 h after AMI. Intestinal ischemia also resulted in lung injury in a time-dependent manner. Pretreatment with NAC decreased the levels of intestinal α-defensins and plasma I-FABP, as well as lung MPO and cytokines. In summary, the concentrations of intestinal α-defensins and plasma I-FABP predicted intestinal ischemia prior to pathological evidence of ischemia and I-FABP directly correlated with resultant lung injury. The antioxidant NAC reduced intestinal and lung injury induced by AMI, suggesting a role for oxidants in the mechanism for distant organ injury. I-FABP and α-defensins are promising biomarkers, and may guide the treatment with antioxidant in early intestinal and distal organ injury.

Intestinal fatty acid binding protein Ala54Thr polymorphism is associated with peripheral atherosclerosis combined with type 2 diabetes mellitus

“…Intestinal fatty acid‐binding protein (FABP2), a 15‐kDa molecule secreted by intestinal columnar epithelial cells, binds to long‐chain fatty acids and plays a vital role in their uptake, transportation, and metabolic regulation . The main function of FABP2 is to transport hydrophobic fatty acids from the cell membrane to the endoplasmic reticulum . The FABP2 protein is encoded by the FABP2 gene, which is located on chromosomal region 4q28–q31 and is composed of four exons and three introns .…”

“…8 The main function of FABP2 is to transport hydrophobic fatty acids from the cell membrane to the endoplasmic reticulum. 9,10 The FABP2 protein is encoded by the FABP2 gene, which is located on chromosomal region 4q28-q31 and is composed of four exons and three introns. 11 A specific polymorphism at codon 54 of the FABP2 gene is thought to have an effect on lipid metabolism.…”

Selective IL-1α exposure to the fetal gut, lung, and chorioamnion/skin causes intestinal inflammatory and developmental changes in fetal sheep

“…This finding was also confirmed by immunohistochemical analysis of I-FABP, a protein that is expressed by intestinal epithelial cells and is released upon epithelial injury. 28,29 We then assessed whether selective IL-1α exposure to different fetal compartments resulted in impaired gut development. Maturation of the fetal gut was assessed by immunohistochemical staining of I-FABP 30 and by the size of vacuoles in the intestinal epithelium.…”

Avaliaçãoo do impacto do diazóxido nas lesões locais e sistêmicas em animais submetidos a isquemia e reperfusão intestinal

“…A oclusão completa da circulação na AMS por uma hora resulta em lesão do epitélio do terço superior dos vilos 75 conforme estudos semelhantes no mesmo modelo 74,76 . Em humanos, enquanto uma isquemia de 30 minutos não causou dano, o tempo de 45 minutos foi suficiente para lesão intestinal irreversível 77,78 . Diante disso, optamos pelo tempo de isquemia de uma hora.…”

“…A isquemia intestinal tem dificuldade em se correlacionar a marcadores séricos, possivelmente por sobreposição de biomarcadores com outros de lesão sistêmica ou pela ação do metabolismo hepático, que degrada substâncias provenientes do intestino através da veia porta 78 . No entanto, a proteína citoplasmática IFABP presente nos enterócitos das extremidades das vilosidades intestinais pode ser encontrada na circulação após a morte destas células 83 , sendo por tal uma forte candidata a marcadora sérica de lesão intestinal 84 .…”