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Title: Evaluation of Antioxidant and Proinflammatory Gene Expression in Bovine Mammary Tissue during the Periparturient Period

item Aitken, S
item Karcher, E
item Rezamand, P
item Gandy, J
item Vandehaar, M
item Capuco, Anthony
item Sordillo, L

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/22/2008
Publication Date: 2/1/2009
Publication URL:
Citation: Aitken, S.L., Karcher, E.L., Rezamand, P., Gandy, J.C., Vandehaar, M.J., Capuco, A.V., Sordillo, L.M. 2009. Evaluation of Antioxidant and Proinflammatory Gene Expression in Bovine Mammary Tissue during the Transition Period. Journal of Dairy Science. 92:589-598.

Interpretive Summary: This study characterized the expression of both antioxidant and pro-inflammatory genes in mammary tissue during the period of time around calving, when the cow is susceptible to bacterial infection of the mammary gland (mastitis). Antioxidants reduce tissue damage from reactive oxygen molecules that are generated to kill invading bacteria and are generated during periods of heightened tissue metabolism, such as lactation. The mRNA expression of antioxidant enzymes was low at approximately 7 d before expected calving, but increased significantly during early lactation. During the transition from pregnancy to lactation, changes in the expression of several antioxidant factors were correlated with changes in the expression of molecules that promote the movement of white blood cells from blood to tissue and expression of some pro-inflammatory molecules. Results from this study suggest that the oxidative state of mammary tissue during the periparturient period may be related to tissue inflammatory responses to mastitis causing pathogens. Ability to control oxidative stress through manipulation of key antioxidant enzymes may help to reduce the incidence and severity of mastitis.

Technical Abstract: The incidence and severity of mastitis can be high during the period of transition from pregnancy to lactation when dairy cattle are susceptible to oxidative stress. Oxidative stress may contribute to the pathogenesis of mastitis by modifying the expression of pro-inflammatory genes. The overall goal of this study was to determine the relationship between critical antioxidant defense mechanisms and pro-inflammatory markers in normal bovine mammary tissue during the periparturient period. Mammary tissue samples were obtained from 12 cows at 35, 20, and 7 d before expected calving and during early lactation (EL, 15 to 28 DIM). Enzyme activities for cytosolic glutathione peroxidase (GPX1) and phospholipid hydroperoxide glutathione peroxidase (GPX4) were relatively low during the dry period, but increased during early lactation (EL), whereas activity of thioredoxin reductase 1 (TrxR1) did not change significantly as a function of time. In contrast, gene expression for these antioxidant selenoproteins and for heme oxygenase-1 (HO-1) gradually decreased as parturition approached and then increased during EL. The expression of intercellular vascular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1) followed a similar trend where mRNA abundance gradually declined as parturition approached with a slight rebound in EL. Gene expression of the pro-oxidant, 15-lipoxygenase 1 (15-LOX1), which is known to increase during times of oxidative stress, also increased dramatically in mammary tissue from EL cows. Expression of the pro-inflammatory cytokines, interleukin (IL)-1ß, IL-6, IL-8 did not change significantly during the periparturient period. Strong positive correlations were found between several antioxidant enzymes (GPX1, TrxR1, and HO-1) and vascular adhesion molecules (ICAM-1, VCAM-1) suggesting a protective response of these antioxidants to an enhanced proinflammatory state. Ability to control oxidative stress through manipulation of key antioxidant enzymes in the future may modify the pro-inflammatory state of periparturient cows and reduce incidence and severity of some diseases, such as mastitis.