Abstract
Dysfunctional inflammation contributes significantly to the pathogenesis of coliform mastitis and the classical pro-inflammatory enzyme cyclooxygenase-2 (COX-2) is the target of medical intervention using the non-steroidal anti-inflammatory drug (NSAID) flunixin meglumine (FM). Inhibition of COX-2 by FM can decrease concentrations of pro-inflammatory fatty acid-based mediators called eicosanoids, providing antipyretic and analgesic effects in dairy cows suffering from coliform mastitis. However, approximately 50% of naturally occurring coliform mastitis with systemic involvement results in death of the animal, even with NSAID treatment. Inadequate antioxidant potential (AOP) to neutralize reactive oxygen species (ROS) produced during excessive inflammation allows for oxidative stress (OS), contributing to tissue damage during coliform mastitis. Biomarkers of lipid peroxidation by ROS, called isoprostanes (IsoP), were used in humans and cattle to quantify the extent of OS. Blood IsoP were shown to be elevated and correlate with oxidant status during acute coliform mastitis. However, the effect of FM treatment on oxidant status and markers of OS has not been established. Blood IsoP concentrations were used to quantify systemic OS, whereas milk was used to assess local OS in the mammary gland. Results indicate that FM treatment had no effect on blood markers of inflammation but reduced the oxidant status index (OSi) by increasing blood AOP from pre- to post-FM treatment. Milk AOP significantly increased from pre- to post-FM treatment, whereas ROS decreased, resulting in a decreased OSi from pre- to post-FM treatment. The only blood IsoP concentration that was significantly different was 5-iso-iPF2α-VI, with a decreased concentration from pre- to post-FM treatment. Conversely, milk 5-iso-iPF2α-VI, 8,12-iso-iPF2α-VI, and total IsoP concentrations were decreased following FM treatment. These results indicated that administration of FM did improve systemic and local oxidant status and reduced local markers of OS. However, differential effects were observed between those animals that survived the infection and those that died, indicating that pre-existing inflammation and oxidant status greatly affect efficacy of FM and may be the key to reducing severity and mortality associated with acute coliform infections. Supplementation to improve AOP and anti-inflammatory mediator production may significantly improve efficacy of FM treatment.
Highlights
IntroductionMastitis is the costliest infectious disease in the US dairy industry, with over $2 billion in annual deficits due to loss of milk production and potential death of the animal [1,2]
Pre-flunixin meglumine (FM) treatment concentrations of haptoglobin, IL-6, and non-esterified fatty acids (NEFAs) were significantly different between infection outcome groups (Figure 1)
Even though no change from pre- to post-FM treatment was observed, NEFA concentrations were no longer significantly elevated among animals that died at 8 h post-FM treatment when compared to those that survived (Figure 1)
Summary
Mastitis is the costliest infectious disease in the US dairy industry, with over $2 billion in annual deficits due to loss of milk production and potential death of the animal [1,2]. Problematic in dairy cows are coliform mastitis cases that are the result of Escherichia coli (E. coli) [2,3,4,5,6]. Targeted breakdown of the mammary epithelium during coliform mastitis results in decline of milk quality and production [7,8,9,10,11,12,13,14]. Some animals mount an effective inflammatory response to clear the pathogen without clinical signs and quickly restore the quality and quantity of milk. Acute coliform infections can Antioxidants 2021, 10, 834.
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