title: Inhibition of neutral sphingomyelinase decreases arachidonic acid mediated inflammation in liver ischemia-reperfusion injury.
abstract: This study aimed to determine the role of selective neutral sphingomyelinase (N-SMase) inhibition on arachidonic acid (AA) mediated inflammation following liver ischemia-reperfusion (IR) injury. Selective N-SMase inhibitor was administered via intraperitoneal injections. Liver IR injury was created by clamping blood vessels supplying the median and left lateral hepatic lobes for 60 min, followed by 60 min reperfusion. Levels of AA in liver tissue were determined by multiple reaction monitoring (MRM) using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Phospholipase A₂ (PLA₂), cyclooxygenase (COX) and prostaglandin E₂ (PGE₂) were measured in liver tissue. Arachidonic acid levels, activity of PLA₂, COX and PGE₂ levels were significantly increased in postischemic liver tissue compared to nonischemic controls. N-SMase inhibition significantly decreased COX activity and PGE₂ levels in postischemic liver. Future studies evaluating agents blocking N-SMase activity can facilitate the development of treatment strategies to alleviate inflammation in liver I/R injury.
authors.affiliation: Department of Medical Biochemistry, Akdeniz University Faculty of Medicine Antalya 07070, Turkey.
authors.forename: Mutay
authors.initials: M
authors.lastname: Aslan
authors.affiliation: Department of Medical Biochemistry, Akdeniz University Faculty of Medicine Antalya 07070, Turkey.
authors.forename: Filiz
authors.initials: F
authors.lastname: Özcan
authors.affiliation: Department of Medical Biochemistry, Akdeniz University Faculty of Medicine Antalya 07070, Turkey.
authors.forename: Hazal
authors.initials: H
authors.lastname: Tuzcu
authors.affiliation: Department of Medical Biochemistry, Akdeniz University Faculty of Medicine Antalya 07070, Turkey.
authors.forename: Ebru
authors.initials: E
authors.lastname: Kıraç
authors.affiliation: Department of Pathology, Akdeniz University Faculty of Medicine Antalya 07070, Turkey.
authors.forename: Gulsum O
authors.initials: GO
authors.lastname: Elpek
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001597:Benzylidene Compounds / Q000494:pharmacology / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D054467:Phospholipases A2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors*
chemical_list: D000814:Aniline Compounds; D001597:Benzylidene Compounds; C468773:GW 4869; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; D054467:Phospholipases A2; D013108:Sphingomyelin Phosphodiesterase; D015232:Dinoprostone
keywords: Arachidonic acid; ischemia-reperfusion injury; liver; neutral sphingomyelinase