Impact of tyloxapol to combat acute phase response in comparison with betamethasone and flunixin meglumine following an ovine experimentally induced endotoxemia model

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 Escherichia coli 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.