title: Propofol Attenuates Small Intestinal Ischemia Reperfusion Injury through Inhibiting NADPH Oxidase Mediated Mast Cell Activation.
abstract: Both oxidative stress and mast cell (MC) degranulation participate in the process of small intestinal ischemia reperfusion (IIR) injury, and oxidative stress induces MC degranulation. Propofol, an anesthetic with antioxidant property, can attenuate IIR injury. We postulated that propofol can protect against IIR injury by inhibiting oxidative stress subsequent from NADPH oxidase mediated MC activation. Cultured RBL-2H3 cells were pretreated with antioxidant N-acetylcysteine (NAC) or propofol and subjected to hydrogen peroxide (H2O2) stimulation without or with MC degranulator compound 48/80 (CP). H2O2 significantly increased cells degranulation, which was abolished by NAC or propofol. MC degranulation by CP further aggravated H2O2 induced cell degranulation of small intestinal epithelial cell, IEC-6 cells, stimulated by tryptase. Rats subjected to IIR showed significant increases in cellular injury and elevations of NADPH oxidase subunits p47(phox) and gp91(phox) protein expression, increases of the specific lipid peroxidation product 15-F2t-Isoprostane and interleukin-6, and reductions in superoxide dismutase activity with concomitant enhancements in tryptase and β-hexosaminidase. MC degranulation by CP further aggravated IIR injury. And all these changes were attenuated by NAC or propofol pretreatment, which also abrogated CP-mediated exacerbation of IIR injury. It is concluded that pretreatment of propofol confers protection against IIR injury by suppressing NADPH oxidase mediated MC activation.
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China ; Zhongshan Ophthalmic Center, Department of Anesthesiology, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Gan
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Xing
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Guangjie
authors.initials: G
authors.lastname: Su
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Chenfang
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, University of Hong Kong, Hong Kong.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Irwin
authors.affiliation: Department of Anesthesiology, University of Hong Kong, Hong Kong.
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology, University of Hong Kong, Hong Kong.
authors.forename: Haobo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Hei
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006861:Hydrogen Peroxide / Q000633:toxicity; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000139:chemically induced / Q000188:drug therapy / Q000401:mortality; D053802:Tryptases / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D001619:beta-N-Acetylhexosaminidases / Q000097:blood; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity
chemical_list: D000975:Antioxidants; D008562:Membrane Glycoproteins; D003189:p-Methoxy-N-methylphenethylamine; D006861:Hydrogen Peroxide; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D001619:beta-N-Acetylhexosaminidases; D053802:Tryptases; D000111:Acetylcysteine; D015742:Propofol