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.
Systemic inflammatory responses to circulating lipopolysaccharide lead to high mortality rates in affected animals and thus effective treatments of this situation are crucial. However, despite different endotoxemia therapeutic regimens, the lack of an effective treatment still remains a clinical problem in sheep. Tyloxapol is a potential pro- and anti-inflammatory molecule to treat endotoxemia in farm animals. Hence, the present study was an attempt to clarify the antiendotoxic effects of tyloxapol in comparison with betamethasone and flunixin meglumine in experimentally induced endotoxemia in sheep. Thirty clinically healthy 1-year old Iranian fat-tailed ewes were randomly divided into 6 equal experimental (n=5) groups, comprising Negative and Positive control, Flunixin meglumine, Betamethasone, Tyloxapol 1 and Tyloxapol 2. Phenol extracted lipopolysaccharide from <em>Escherichia coli</em> serotype O55:B5 was infused at 2 μg/kg intravenously. Ninety min after endotoxemia induction, Flunixin meglumine (2.2 mg/kg), betamethasone (1 mg/kg) and tyloxapol (200 and 400 mg/kg) were injected to respective groups, 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 hours after lipopolysaccharide injection and sera and plasmas were separated, subsequently. Haptoglobin, serum amyloid A, tumor necrosis factor-alpha, interferon-gamma, superoxide dismutase and glutathione peroxidase were measured in all samples. Serum concentrations of haptoglobin, serum amyloid A, tumor necrosis factor-alpha, interferongamma in Flunixin meglumine group were found to be lower than other experimental ones after hour 3. Serum levels of haptoglobin, serum amyloid A, tumor necrosis factor-alpha, interferon-gamma in Tyloxapol groups were significantly lower and higher than Betamethasone and Flunixin meglumine ones, respectively. Superoxide dismutase and glutathione peroxidase activities in Flunixin meglumine group were significantly higher than other experimental groups after administration of drugs. In conclusion, the efficacy of tyloxapol was significantly higher and lower than betamethasone and flunixin meglumine, respectively. Furthermore, tyloxapol doesn’t induce its effects by dose dependent manner and its anti- and pro-inflammatory effects at 200 and 400 mg/kg were statistically similar.
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