Chih-Cheng Luo1, Chen-Sheng Huang1, Yung-Ching Ming2, Shih-Ming Chu3, Hsun-Chin Chao4. 1. Division of Pediatric Surgery, Department of Surgery, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan. 2. Department of Pediatric Surgery, Chang Gung Children's Medical Center, Chang Gung Memorial Hospital, Guishan, Taoyuan, Taiwan. 3. Division of Neonatology, Chang Gung Children's Medical Center, Chang Gung Memorial Hospital, Guishan, Taoyuan, Taiwan. 4. Division of Pediatric Gastroenterology, Chang Gung Children's Medical Center, Chang Gung Memorial Hospital, Guishan, Taoyuan, Taiwan. Electronic address: chaohero@yahoo.com.
Abstract
BACKGROUND: Various investigations have demonstrated that calcitonin gene-related peptide (CGRP) plays an important role in mediating ischemic preconditioning. CGRP has been shown to mimic the protective effects of ischemic preconditioning and mitigate ischemia-reperfusion (I/R) injury in the heart, brain, gastrointestinal system, and other tissues. This study aimed to examine whether CGRP, a proven intestinal cytoprotective molecule, exerted its protective effects through modulation of inducible nitride oxide synthase (iNOS) and apoptosis after intestinal I/R injury. METHODS: This animal study randomly divided 30 rats into the following five groups: (1) the normal control group, (2) the ischemia group with normal saline, (3) the I/R group with normal saline, (4) the ischemia group with CGRP (300 μg/kg), and (5) the I/R group with CGRP (300 μg/kg). Levels of iNOS messenger RNA (mRNA) and protein, and caspase-3 protein were determined by real-time quantitative polymerase chain reaction and Western blotting analyses, respectively. Statistical analysis was performed using analysis of variance with Dunn test. RESULTS: The mRNA levels of iNOS increased after the intestinal ischemia or intestinal reperfusion phase (p < 0.01), and CGRP pretreatment significantly decreased iNOS mRNAs and protein levels (p < 0.01). The expression protein levels of caspase-3 increased after the intestinal ischemia or intestinal reperfusion phase. CGRP pretreatment significantly decreased the levels of caspase-3 proteins. CGRP intestinal cytoprotection is mediated, in part, by downregulation of expression of iNOS and caspase-3 after intestinal I/R injury. CONCLUSION: The study indicates that the cytoprotective role of CGRP (i.e., antiapoptotic effect) after I/R injury could be via downregulation of iNOS, which may relieve I/R tissue damage by blocking iNOS activity.
BACKGROUND: Various investigations have demonstrated that calcitonin gene-related peptide (CGRP) plays an important role in mediating ischemic preconditioning. CGRP has been shown to mimic the protective effects of ischemic preconditioning and mitigate ischemia-reperfusion (I/R) injury in the heart, brain, gastrointestinal system, and other tissues. This study aimed to examine whether CGRP, a proven intestinal cytoprotective molecule, exerted its protective effects through modulation of inducible nitride oxide synthase (iNOS) and apoptosis after intestinal I/R injury. METHODS: This animal study randomly divided 30 rats into the following five groups: (1) the normal control group, (2) the ischemia group with normal saline, (3) the I/R group with normal saline, (4) the ischemia group with CGRP (300 μg/kg), and (5) the I/R group with CGRP (300 μg/kg). Levels of iNOS messenger RNA (mRNA) and protein, and caspase-3 protein were determined by real-time quantitative polymerase chain reaction and Western blotting analyses, respectively. Statistical analysis was performed using analysis of variance with Dunn test. RESULTS: The mRNA levels of iNOS increased after the intestinal ischemia or intestinal reperfusion phase (p < 0.01), and CGRP pretreatment significantly decreased iNOS mRNAs and protein levels (p < 0.01). The expression protein levels of caspase-3 increased after the intestinal ischemia or intestinal reperfusion phase. CGRP pretreatment significantly decreased the levels of caspase-3 proteins. CGRP intestinal cytoprotection is mediated, in part, by downregulation of expression of iNOS and caspase-3 after intestinal I/R injury. CONCLUSION: The study indicates that the cytoprotective role of CGRP (i.e., antiapoptotic effect) after I/R injury could be via downregulation of iNOS, which may relieve I/R tissue damage by blocking iNOS activity.
Authors: Gustavo Sampaio de Holanda; Samuel Dos Santos Valença; Amabile Maran Carra; Renata Cristina Lopes Lichtenberger; Bianca de Castilho; Olavo Borges Franco; João Alfredo de Moraes; Alberto Schanaider Journal: Metabolites Date: 2021-11-26