Attenuating the endotoxin induced acute phase response by pentoxifylline in comparison with dexamethasone and ketoprofen in sheep

• Endotoxemia is a common cause of high mortality rates in sheep rearing systems.
• The effective therapeutic regimens against this situation are necessary.
• Several treatment protocols have been suggested by researchers.
• Using new potential drugs such as pentoxifylline can be effective against endotoxemia.
• The present study reveals the efficacy of pentoxifylline in treating ovine endotoxemia.

Treating the endotoxemia in animals is necessary to prevent high mortality rates. Despite the suggestion of different endotoxemia therapeutic regimens, the lack of an effective treatment still remains a clinical problem in sheep. Hence, the present study was performed to clarify the antiendotoxic effects of pentoxifylline in comparison with dexamethasone and ketoprofen 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, ketoprofen (3 mg/kg), dexamethasone (1 mg/kg) and pentoxifylline (30 and 60 mg/kg). Lipopolysaccharide from Escherichia coli serotype O55:B5 was infused at 2 μg/kg intravenously. Ketoprofen, dexamethasone and pentoxifylline were injected to related groups, 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, interferon-gamma, superoxide dismutase and glutathione peroxidase were measured in all samples. Serum levels of haptoglobin, serum amyloid A, tumor necrosis factor-alpha, interferon-gamma in both pentoxifylline groups were significantly lower and higher than dexamethasone and ketoprofen ones, respectively. In conclusion, the efficacy of pentoxifylline was significantly higher and lower than dexamethasone and ketoprofen, respectively. Furthermore, its anti- and pro-inflammatory effects at 30 and 60 mg/kg were statistically similar together.