Study of Oxidative Stress Biomarkers in Equids Affected by Systemic Inflammatory Response Syndrome and Sepsis

Systemic inflammatory response syndrome (SIRS) and sepsis remain major causes of morbidity and mortality in equine medicine. Early identification of disease severity and prognosis is often challenging, and there is growing interest in the use of circulating biomarkers to evaluate oxidative stress, antioxidant responses and endothelial dysfunction as key components of these conditions. This thesis investigates a panel of such biomarkers across adult horses with colic and ill neonatal foals, combining methodological assay validation with clinical studies to assess their diagnostic and prognostic potential. The work begins with a methodological evaluation of paraoxonase-1 (PON1) activity, assessing the influence of storage temperature, freeze–thaw cycles and simulated transport on two PON1 activities (arylesterase and paraoxonase) in equine serum and heparinised plasma. The findings demonstrate significant sensitivity of PON1 to pre-analytical conditions, with marked deterioration at –20 °C and greater stability at –80 °C. This chapter establishes essential methodological standards to ensure reliable interpretation of PON1 and related oxidative biomarkers in subsequent studies. In adult horses with colic, two clinical investigations examined dimethylarginines (ADMA and SDMA) and a broader oxidative stress panel. ADMA and SDMA concentrations differed between healthy horses and colic cases and were associated with lesion type and systemic inflammatory status, highlighting their relevance as indicators of endothelial dysfunction. The oxidative stress study revealed that colic induces a distinct redox imbalance characterised by changes in paraoxonase activities, lipid peroxidation and several antioxidant enzymes. These alterations varied between non-strangulating and strangulating lesions and were associated with survival, suggesting potential prognostic value. The final study extended this biomarker approach to ill neonatal foals, evaluating oxidative stress and antioxidant responses in healthy, sick non-septic and septic individuals. Despite limited sample size, the results demonstrated measurable alterations in oxidative status among ill foals and identified associations with sepsis scores and survival indicators. These findings support the involvement of oxidative imbalance in neonatal systemic disease and highlight the potential for biomarker-guided assessment in foal medicine. Together, the studies in this thesis demonstrate that in the course of SIRS and sepsis secondary to a variety of common clinical pathologies in both adult horses and foals, there is a clear perturbation of the redox state. This disturbance is characterized by a reduction in antioxidant activities and a concomitant increase in oxidation products, reflecting a shift toward oxidative imbalance. Rather than focusing on immediate clinical application, this work primarily contributes to the descriptive understanding of how oxidative pathways are altered during SIRS and sepsis in equine patients. By documenting these changes across different age groups and disease processes, the thesis provides a detailed portrayal of the redox disturbances that accompany naturally occurring equine inflammatory disease and offers a solid foundation for future mechanistic and translational research.