Role of lipid mediators in the regulation of oxidative stress and inflammatory responses in dairy cattle.

Periparturient dairy cows experience an increased incidence and severity of several inflammatory-based diseases such as mastitis and metritis. Factors associated with the physiological adaptation to the onset of lactation can impact the efficiency of the inflammatory response at a time when it is most needed to eliminate infectious pathogens that cause these economically important diseases. Oxidative stress, for example, occurs when there is an imbalance between the production of oxygen radicals during periods of high metabolic demand and the reduced capabilities of the host's antioxidant defenses. The progressive development of oxidative stress in early lactation cows is thought to be a significant underlying factor leading to dysfunctional inflammatory responses. Reactive oxygen species (ROS) are also produced by leukocytes during inflammation resulting in positive feedback loops that can further escalate oxidative stress during the periparturient period. During oxidative stress, ROS can modify polyunsaturated fatty acids (PUFA) associated with cellular membranes, resulting in the biosynthesis of oxidized products called oxylipids. Depending on the PUFA substrate and oxidation pathway, oxylipids have the capacity of either enhancing or resolving inflammation. In mediating their effects, oxylipids can directly or indirectly target sites of ROS production and thus control the degree of oxidative stress. This review discusses the evidence supporting the roles of oxylipids in the regulation of oxidative stress and the subsequent development of uncontrolled inflammatory responses. Further, the utility of some of the oxylipids as oxidative stress markers that can be exploited in developing and monitoring therapies for inflammatory-based diseases in dairy cattle is discussed. Understanding of the link between some oxylipids and the development or resolution of oxidative stress could provide novel therapeutic targets to limit immunopathology, reduce antibiotic usage, and optimize the resolution of inflammatory-based diseases in periparturient dairy cows.