There have been insufficient studies of S. pluranimalium infection in sheep worldwide. Therefore, this study aimed to evaluate the acute-phase response and oxidative status in infected sheep. While this bacterium causes problems with endocarditis and brain abscess in humans
4-6, it is reported that it causes mastitis, abortion, and stillbirths in cattle
2,3, meningoventriculitis in a calf
31, respiratory disease in dogs
32, and septicaemia and endocarditis in broiler chickens
33. On the other hand, in only one report, Foster et al.
34 isolated the agent from two sheep abortion materials, especially from stomach and liver samples of the fetus. At the same time, as clinical findings, it was reported that the sheep were pyrexic at the time of the abortion. In the presented study, pyrexia, anorexia, excessive weakening, weight loss, necrotic ulcerative dermatitis in the tail area (Figure
1), and death within 5 to 10 days were important clinical findings in the infected sheep.
Common causes of oxidative stress are infections, inflammation, and toxaemias 35. Infections and inflammations activate inflammatory cells that play important roles in the host’s defense 15. Since major inflammatory cells, such as neutrophils and/or macrophages, generate a variety of ROS and release various proteases, tissue damage and destruction occur 15,35. In addition, one of the many biological targets of oxidative stress is lipids. PUFAs, in particular, are the frequently targeted class of biomolecules. ROS-induced oxidation of PUFAs in biological systems results in the formation of LPO products 15,35. MDA is a breakdown product that is quantified as a measure of lipid hydroperoxides, and is accepted as an indicator of elevated oxidative stress in the body 36,37. In sheep, oxidant status has been identified in metabolic 38,39, parasitic 9,10,40, and viral diseases 11,12, as well as in physiological conditions, such as age 41 and pregnancy 42. In the present study, serum MDA levels were significantly increased in infected sheep compared to healthy sheep (P<0.01). In this case, it has been consistent with the previous reports. These increases can be considered as an indicator of excessive free radical production in infected sheep.
NO is a prominent molecule in defense against many microorganisms 17,18. NO, which is produced by macrophages in bacterial infections, shows antibacterial properties against bacteria and host defense depends on the concentration of NO 18. It was reported that NO concentrations in animals with bacterial 19,20, viral 11,21,22 and parasitic diseases 23 increased compared to healthy controls. In addition, it has been determined that NO levels increase in bacterial diseases such as traumatic reticuloperitonitis 43 and traumatic pericarditis 44. Similarly, in the present study, NO concentrations were high in infected sheep as in the above reports. This increase was thought due to inducing of NO synthesis by macrophages defending the organism against infection.
Haptoglobin belongs to a group of transporter plasma proteins that bind the free haemoglobin 45. This defines its bacteriostatic effect as well as antioxidant activity 26,45 Many studies have demonstrated the importance of Hp as a clinically helpful parameter for measuring the occurrence and severity of inflammatory responses in sheep with various infectious diseases 12,46-52.
Pepin et al. 46 investigated the changes in Hp concentrations in lambs experimentally infected by Corynebacterium pseudotuberculosis. They reported the rapidly increasing Hp concentration to peak in plasma after subcutaneous inoculation. In a similar study, Eckersall et al. 47 explored the differences in plasma levels of Hp during experimental ovine caseous lymphadenitis induced by C. pseudotuberculosis. The results showed significantly raised Hp concentrations on day 7 after inoculation and these values were statistically significant until the 15th day. In another study, Bastos et al. 49 also stated that there was no significant difference between serum Hp concentrations in seropositive and seronegative sheep during caseous lymphadenitis in Santa-Ines sheep. However, later in 11 sheep that have not developed peripheral abscesses, a significantly higher Hp concentration was observed. Fasulkov et al. 50 investigated plasma Hp concentrations during experimentally induced Staphylococcos aureus mastitis in goats and showed an increase of the Hp as early as the 8th hour with the most significant differences from baseline values by the 24th and 48th h after infection. On the other hand, Chalmeh et al. 51 found a rapid elevation in Hp levels during experimentally induced endotoxaemia in sheep by lipopolysaccharide from Escherichia coli. In the present study, Hp concentrations were significantly higher in infected sheep (Hp; 0.17±0.01g/L versus 0.11±0.01g/L) compared to the healthy control group (P<0.001). These values were observed to be similar to different studies conducted in previous years 45-49. Therefore, it can be said that Hp concentrations are important in the pathogenesis and monitoring of S. pluranimalium infection. In addition, there was a significantly positive correlation between Hp and MDA levels of the infected sheep (P<0.05). These findings may indicate that APR and oxidative damage occurs simultaneously in infected sheep and triggers each other.
Albumin is the major negative APP. During the APR the demand for amino acids for synthesis of the positive APPs is markedly increased, which necessitates reprioritization of hepatic protein synthesis. Therefore, Alb synthesis is down-regulated and amino acids are shunted into the synthesis of positive APPs 53,54. In addition, it has been stated that the serum concentrations of Alb, are affected by impaired liver function, reduced intestinal absorption, and starvation 24,55. In the presented study, the serum Alb concentrations in infected sheep were not statistically different from the control group. However, the decrease in Alb concentration may be related to the synthesis of APPs and this finding may indicate that hepatic Alb synthesis was affected by APR.
In conclusion, high serum MDA and NO levels indicate that oxidative stress takes place in naturally infected sheep with S. pluranimalium. Higher Hp and low Alb concentrations in the infected animals compared to the healthy ones is also an indicator of APR in these animals.
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