Inhibition of neutral sphingomyelinase decreases arachidonic acid mediated inflammation in liver ischemia-reperfusion injury

Aslan M., Ozcan F., Tuzcu H., Kirac E., ELPEK G. Ö.

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY, cilt.7, sa.11, ss.7814-7823, 2014 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 7 Sayı: 11
  • Basım Tarihi: 2014
  • Doi Numarası: 10.2555/0821
  • Dergi Adı: INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED)
  • Sayfa Sayıları: ss.7814-7823
  • Anahtar Kelimeler: Arachidonic acid, liver, ischemia-reperfusion injury, neutral sphingomyelinase, POLYUNSATURATED FATTY-ACIDS, PHOSPHOLIPASE A(2), RAT-LIVER, HEPATIC ISCHEMIA/REPERFUSION, ENDOTHELIAL-CELLS, PROSTAGLANDIN E-2, KUPFFER CELLS, GROUP IIA, CYCLOOXYGENASE-2, TRANSPLANTATION
  • Akdeniz Üniversitesi Adresli: Evet

Özet

Int J Clin Exp Pathol. 2014 Oct 15;7(11):7814-23. eCollection 2014. Inhibition of neutral sphingomyelinase decreases arachidonic acid mediated inflammation in liver ischemia-reperfusion injury. Aslan M1, Özcan F1, Tuzcu H1, Kıraç E1, Elpek GO2. Author information 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. KEYWORDS: Arachidonic acid; ischemia-reperfusion injury; liver; neutral sphingomyelinase

 2014 Oct 15;7(11):7814-23. eCollection 2014.

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.

KEYWORDS:

Arachidonic acid; ischemia-reperfusion injury; liver; neutral sphingomyelinase