title: The comparative efficacy of tyloxapol versus pentoxifylline against induced acute phase response in an ovine experimental endotoxemia model.
abstract: The effective treatments of endotoxemia are necessary to prevent high mortality rates. Hence, the present study was performed to clarify the antiendotoxic effects of tyloxapol and pentoxifylline in experimentally induced endotoxemia in sheep. Thirty clinically healthy 1-year-old Iranian fat-tailed ewes were randomly divided into six equal experimental (n = 5) groups, comprising Negative and Positive control, Tyloxapol 1, Tyloxapol 2, Pentoxifylline 1 and Pentoxifylline 2. Phenol extracted lipopolysaccharide from Escherichia coli serotype O55:B5 was infused at 2 µg/kg intravenously. Tyloxapol (200 and 400 mg/kg) and pentoxifylline (30 and 60 mg/kg) were injected to Tyloxapol and Pentoxifylline groups, respectively, at 90 min after endotoxemia induction over 60 min along with intravenous fluids. Blood samples were collected from all ewes prior and 1.5, 3, 4.5, 6, 24 and 48 h after lipopolysaccharide injection and sera and plasmas were separated, subsequently. Haptoglobin, serum amyloid A, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), superoxide dismutase and glutathione peroxidase were measured in all samples. Serum concentrations of haptoglobin, serum amyloid A, TNF-α and IFN-γ in Tyloxapol 1 and 2 and Pentoxifylline 1 and 2 groups were significantly lower than Positive control one after hour 3. There were no significant differences among Tyloxapol and Pentoxifylline groups (P > 0.05). Superoxide dismutase and glutathione peroxidase activities in Tyloxapol 1 and 2 and Pentoxifylline 1 and 2 groups were significantly lower than Positive control one after hour 3. There were no significant differences among Tyloxapol 1 and 2 and Pentoxifylline 1 and 2 groups (P > 0.05). Tyloxapol and pentoxifylline act as the anti-inflammatory mediators by decreasing pro-inflammatory cytokines and hepatic APPs and modulating oxidative enzymes activity after endotoxemia induction in sheep. Furthermore, their efficacies at different doses were significantly similar together and both drugs don't induce their effects by dose dependent manner and the anti- and pro-inflammatory effects of them were statistically similar.
authors.affiliation: Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, P.O. Box 71345, Iran. achalmeh81@gmail.com.
authors.forename: Aliasghar
authors.initials: A
authors.lastname: Chalmeh
authors.affiliation: Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, P.O. Box 71345, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Rahmani Shahraki
authors.affiliation: Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, P.O. Box 71345, Iran.
authors.forename: Seyed Mohammad Mehdi
authors.initials: SM
authors.lastname: Heidari
authors.affiliation: Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, P.O. Box 71345, Iran.
authors.forename: Khalil
authors.initials: K
authors.lastname: Badiei
authors.affiliation: Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, P.O. Box 71345, Iran.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Pourjafar
authors.affiliation: Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, P.O. Box 71345, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Nazifi
authors.affiliation: Department of Animal Sciences, College of Agriculture Science, Shiraz University, Shiraz, Iran.
authors.forename: Mohammad Javad
authors.initials: MJ
authors.lastname: Zamiri
mesh_terms: D000210:Acute-Phase Reaction / Q000188:drug therapy*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000188:drug therapy*; D004926:Escherichia coli / Q000737:chemistry; D005260:Female; D008070:Lipopolysaccharides / Q000633:toxicity; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D011092:Polyethylene Glycols; D010431:Pentoxifylline; C016811:tyloxapol
keywords: Endotoxemia; Inflammatory responses; Pentoxifylline; Sheep; Treatment; Tyloxapol