PMID- 30768981 OWN - NLM STAT- MEDLINE DCOM- 20190806 LR - 20190806 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 850 DP - 2019 May 5 TI - The effect of exenatide (a GLP-1 analog) and sitagliptin (a DPP-4 inhibitor) on plasma platelet-activating factor acetylhydrolase (PAF-AH) activity and concentration in normal and fructose-fed rats. PG - 180-189 LID - S0014-2999(19)30106-2 [pii] LID - 10.1016/j.ejphar.2019.02.014 [doi] AB - Inflammation and oxidative stress are the two processes crucial in atherogenesis. Platelet-activating factor acetylhydrolase (PAF-AH), a plasma lipoprotein-associated enzyme, degrades pro-inflammatory lipids generated within oxidatively modified lipoproteins. Extensive evidence shows that incretin-based drugs, a new class of anti-diabetic agents, can provide cardiovascular protection that cannot be attributed to their glucose-lowering effects. The present study was undertaken to determine whether the antiatherogenic effects of the GLP-1(glucagon-like peptide-1) receptor agonist (exenatide) and DPP-4(dipeptidyl peptidase-4) inhibitors (sitagliptin) may occur via the regulation of platelet-activating factor acetylhydrolase (PAF-AH) activity/mass and inhibition of low-density lipoprotein (LDL) oxidation in the fructose-fed rats. Normal and fructose-fed rats (8 wk) were treated (4 wk) with sitagliptin (5 and 10 mg/kg p.o.) or with exenatide (5 and 10 microg/kg, s.c.). Plasma PAF-AH activity and phosphatidylcholine (PC) concentration were measured colorimetrically. Plasma PAF-AH concentration, oxidized LDL (oxLDL), hexanoyl-Lys adduct (HEL), lyso-PC, apolipoprotein A-I (apoA-I), apoB, platelet-activating factor (PAF), monocyte chemoattractant protein-1 (MCP-1) and endothelin-1 (ET-1) were measured by ELISA. The four-week exenatide (5 microg/kg, sc.) treatment of fructose fed-rats significantly increased plasma PAF-AH activity (+33%, P < 0.001) and decreased the level of circulating oxLDL (-42%, P < 0.05) and MCP-1 (-23%, P < 0.01). These changes were accompanied by the decrease in plasma PC/lyso-PC (-47%, P < 0.001) and apoB/apoA-I ratio (-75%, P < 0.001). The effect of exenatide on enzyme activity was associated with only a minor effect on metabolic parameters and was independent of weight reduction. Exenatide but not sitagliptin inhibits oxidative modification of LDL probably due to favorable effect on plasma PAF-AH activity. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Wojcicka, Grazyna AU - Wojcicka G AD - Department of Pathophysiology, Medical University of Lublin, ul. Jaczewskiego 8b, 20-090 Lublin, Poland. Electronic address: grazyna.wojcicka@umlub.pl. FAU - Zareba, Mariusz AU - Zareba M AD - Department of Pathophysiology, Medical University of Lublin, ul. Jaczewskiego 8b, 20-090 Lublin, Poland. Electronic address: mzareba87@wp.pl. FAU - Warpas, Anna AU - Warpas A AD - Department of Pathophysiology, Medical University of Lublin, ul. Jaczewskiego 8b, 20-090 Lublin, Poland. Electronic address: anna.warpas@umlub.pl. FAU - Jamroz-Wisniewska, Anna AU - Jamroz-Wisniewska A AD - Department of Neurology, Medical University of Lublin, ul. Jaczewskiego 8, 20-090 Lublin, Poland. Electronic address: anna.jamroz@umlub.pl. FAU - Rusek, Marta AU - Rusek M AD - Department of Pathophysiology, Medical University of Lublin, ul. Jaczewskiego 8b, 20-090 Lublin, Poland. Electronic address: marta.rusek@umlub.pl. FAU - Czechowska, Grazyna AU - Czechowska G AD - Department of Pharmacology, Medical University of Lublin, ul. Chodzki 4a, 20-093 Lublin, Poland. Electronic address: grazyna.czechowska@umlub.pl. FAU - Beltowski, Jerzy AU - Beltowski J AD - Department of Pathophysiology, Medical University of Lublin, ul. Jaczewskiego 8b, 20-090 Lublin, Poland. Electronic address: jerzy.beltowski@umlub.pl. LA - eng PT - Journal Article DEP - 20190212 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Biomarkers) RN - 30237-26-4 (Fructose) RN - 9P1872D4OL (Exenatide) RN - EC 3.1.1.47 (1-Alkyl-2-acetylglycerophosphocholine Esterase) RN - TS63EW8X6F (Sitagliptin Phosphate) MH - 1-Alkyl-2-acetylglycerophosphocholine Esterase/*blood/metabolism MH - Animals MH - Biomarkers/metabolism MH - Body Weight/drug effects MH - Eating/drug effects MH - Exenatide/*pharmacology MH - Fructose/*adverse effects MH - Male MH - Oxidative Stress/drug effects MH - Rats MH - Rats, Wistar MH - Sitagliptin Phosphate/*pharmacology OTO - NOTNLM OT - Exenatide OT - Fructose OT - Lysophosphatidylcholine OT - Oxidative LDL OT - Platelet activating factor acetylhydrolase OT - Sitagliptin EDAT- 2019/02/16 06:00 MHDA- 2019/08/07 06:00 CRDT- 2019/02/16 06:00 PHST- 2018/10/18 00:00 [received] PHST- 2019/02/04 00:00 [revised] PHST- 2019/02/11 00:00 [accepted] PHST- 2019/02/16 06:00 [pubmed] PHST- 2019/08/07 06:00 [medline] PHST- 2019/02/16 06:00 [entrez] AID - S0014-2999(19)30106-2 [pii] AID - 10.1016/j.ejphar.2019.02.014 [doi] PST - ppublish SO - Eur J Pharmacol. 2019 May 5;850:180-189. doi: 10.1016/j.ejphar.2019.02.014. Epub 2019 Feb 12.