PMID- 34978390 OWN - NLM STAT- MEDLINE DCOM- 20220524 LR - 20220716 IS - 2053-1095 (Electronic) IS - 2053-1095 (Linking) VI - 8 IP - 3 DP - 2022 May TI - Un-fractionated heparin counteracts the systemic inflammatory responses and multiple organ damages caused by endotoxaemia in sheep. PG - 1187-1196 LID - 10.1002/vms3.720 [doi] AB - BACKGROUND: Endotoxaemia is believed to be a major cause of mortality and there are several therapeutic regimens for the treatment of this situation. OBJECTIVES: The present experimental study was conducted to evaluate acute phase response, cardiovascular and hepatorenal damages following the treatment of Ovine experimental endotoxaemia model employing unfractionated heparin (UFH). MATERIALS AND METHODS: Twenty clinically healthy 1-year-old fat-tailed ewes were randomly divided into four equal groups, comprising UFH 200, UFH 400, Ctrl+ and Ctrl-. Lipopolysaccharide (LPS) from Escherichia coli serotype O55:B5 at 0.4 mug/kg was administered intravenously to the ewes. UFH (at 200 and 400 IU/kg) was administrated to the UFH 200 and UFH 400 groups, respectively. All the ewes were evaluated clinically before and 1.5, 3, 4.5, 6 and 24 hours after LPS injection. Blood samplings were also performed at those hours. We measured serum concentrations of haptoglobin, interferon-gamma, total antioxidant status, malondialdehyde, cardiac lactate dehydrogenase, cardiac troponin-I, total bilirubin, alanine transaminase and creatinine. Serum concentrations of acute phase response, cardiovascular, hepatic and renal biomarkers and clinical parameters increased significantly following the induction of endotoxaemia in the groups receiving LPS. RESULTS: The significantly lowest concentrations of these parameters at hours 4.5 and 6 among the treatment groups belonged to the UFH 400 sheep. CONCLUSIONS: UFH could act as an anti-inflammatory mediator by decreasing inflammatory cytokines and acute phase proteins, modulating oxidative stress biomarkers and reducing multiple organ dysfunction following endotoxaemia in a dose-dependent manner. Furthermore, the anti-inflammatory effects of UFH at 400 IU/kg were significantly higher than another dose. This research examined the effect of two doses of UFH and higher doses may have more anti-inflammatory effects that require further studies. CI - (c) 2021 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd. FAU - Ashareyoun, Hesam AU - Ashareyoun H AD - Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran. FAU - Chalmeh, Aliasghar AU - Chalmeh A AUID- ORCID: 0000-0001-8673-2541 AD - Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran. FAU - Pourjafar, Mehrdad AU - Pourjafar M AD - Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220103 PL - England TA - Vet Med Sci JT - Veterinary medicine and science JID - 101678837 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Biomarkers) RN - 0 (Lipopolysaccharides) RN - 9005-49-6 (Heparin) SB - IM MH - Acute-Phase Reaction/drug therapy/veterinary MH - Animals MH - Anti-Inflammatory Agents MH - Biomarkers MH - *Endotoxemia/chemically induced/drug therapy/veterinary MH - Escherichia coli MH - Female MH - Heparin/pharmacology/therapeutic use MH - Lipopolysaccharides/toxicity MH - Sheep MH - *Sheep Diseases/chemically induced/drug therapy PMC - PMC9122390 OTO - NOTNLM OT - endotoxaemia OT - inflammation OT - multiple organ dysfunction OT - sheep OT - unfractionated heparin COIS- The authors declare no conflict of interest. EDAT- 2022/01/04 06:00 MHDA- 2022/05/25 06:00 PMCR- 2022/01/03 CRDT- 2022/01/03 09:35 PHST- 2022/01/04 06:00 [pubmed] PHST- 2022/05/25 06:00 [medline] PHST- 2022/01/03 09:35 [entrez] PHST- 2022/01/03 00:00 [pmc-release] AID - VMS3720 [pii] AID - 10.1002/vms3.720 [doi] PST - ppublish SO - Vet Med Sci. 2022 May;8(3):1187-1196. doi: 10.1002/vms3.720. Epub 2022 Jan 3.