Effects of nitroglycerin and flunixin meglumine on circulating inflammatory, cardiovascular and hepatorenal biomarkers of ovine experimental endotoxemia model

Abstract

Owing to the importance of endotoxemia and its risks, several studies have been conducted to better understand the pathophysiological processes of this disease, and many treatments have been suggested. Nitroglycerin is one of the drugs recommended for the treatment of endotoxemia and its therapeutic effects in some researches have been evaluated in human and animal models. However, there are no comprehensive studies on the effects of nitroglycerin on different circulating inflammatory, cardiovascular and hepatorenal biomarkers following endotoxemia in sheep; therefore, the present experiment was conducted to evaluate the anti-inflammatory effects of two different doses of nitroglycerin compared to the standard dose of flunixin meglumine in the treatment of endotoxemia in sheep. Hence, 25 clinically healthy 1-year old Iranian fat-tailed ewes were randomly divided into 5 equal groups, comprising NTG 0.2, NTG 0.4, Flnx, Ctrl+, and Ctrl-. Lipopolysaccharide from Escherichia coli serotype O55:B5 at 0.4 μg/kg was intravenously administered to the ewes. Flunixin meglumine (at 2.2 mg/kg) and nitroglycerin (at 0.2 and 0.4 μg/kg) were administrated to Flnx, NTG 0.2 and NTG 0.4 groups, respectively. All the ewes were clinically evaluated before and 1.5, 3, 3.5, 4, 4.5, 6 and 24 h after lipopolysaccharide injection, and blood samplings were also performed at those hours. Serum concentrations of haptoglobin, serum amyloid A, tumor necrosis factor-alpha, interferon-gamma, total antioxidant status, malondialdehyde, superoxide dismutase, glutathione peroxidase, creatine kinase-MB, cardiac lactate dehydrogenase, cardiac troponin-I, homocysteine, total bilirubin, aspartate aminotransferase, alanine transaminase, and creatinine were measured. Serum concentrations of acute phase proteins, inflammatory cytokines, oxidative stress, cardiovascular, hepatic and renal biomarkers, and clinical parameters were significantly increased following the induction of endotoxemia in the groups receiving lipopolysaccharide. The results indicated that nitroglycerin at both 0.2 and 0.4 μg/kg did not play an effective role in reducing inflammatory biomarkers and could not reduce circulating hepatic biomarkers following endotoxemia. However, nitroglycerin at 0.4 μg/kg significantly reduced circulating cardiac and renal biomarkers compared to 0.2 μg/kg and flunixin meglumine at 2.2 mg/kg. Clinical evaluations also demonstrated that nitroglycerin could not reduce the heart rate and body temperature compared to flunixin meglumine but significantly reduced respiratory rates at 0.4 μg/kg. In conclusion, nitroglycerin at 0.2 and 0.4 μg/kg could not alleviate inflammatory processes and oxidative stress. Nitroglycerin at 0.2 and 0.4 μg/kg also had suitable effects on reducing the serum concentration of cardiovascular and renal biomarkers, but it was not effective on circulating hepatic indices. Therefore, nitroglycerin at the doses used in this study could not be suggested as an effective drug in reducing inflammatory and hepatic biomarkers which were elevated during endotoxemia in sheep.