Effect of 2,4-thiazolidinedione treatment in the inflammatory response to induced sub-clinical mastitis in dairy goats receiving adequate vitamin supplementation

Abstract Text: Mastitis is one of the most costly diseases for the dairy industry. A prior experiment in our laboratory indicated a positive role of 2,4-thiazolidinedione (TZD), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, on the inflammatory response after induced subclinical mastitis in dairy goats fed hay without supplements. Despite this, lack of effect on expression of targets genes in adipose tissue and mammary cells and in vitro data suggested the possibility that TZD did not activate PPARg due to an insufficient activation of its obligate heterodimer nuclear receptor RXR by 9-cis-retinoic, a metabolite of vitamin A. This study investigated the hypothesis that continuous activation of PPARγ by TZD in goats supplemented with adequate amount of vitamin A can improve inflammatory response to sub-clinical mastitis in lactating dairy goats. To test this, 12 Saanen multiparous goats in mid-lactation received a diet that met NRC requirements, including vitamin A. Does received daily intrajugular injection of either TZD (n=6) or saline (n=6; CTRL). Following 14 days of treatments, all goats received intramammary infusion (IMI) of Streptococcus uberis to induce sub-clinical mastitis in the right half with the left half used as control. Metabolic, inflammation, and oxidative-status profiling in blood including 19 parameters was performed. Milk yield and SCC and rectal temperature were assessed. Data were analyzed by GLIMMIX of SAS with treatment (TRT) and Time and TRTxTime interaction as main effects and goat as random effect. For milk and SCC, mammary half was also included in the main effect (including interactions). Significance was declared at Tukey’s corrected P<0.05. Milk yield and SCC were not affected by TZD administration. However the udder receiving IMI had greater SCC. In blood within 2 days from IMI, ceruloplasmin, haptoglobin, and glucose were increased while Zn was decreased. At 3 day post-IMI AST/GOT, gGT, and bilirubin decreased, while by 6-11 days post-IMI urea, protein, albumin, globulin, NEFA, and creatinine increased. All these data confirmed successful induction of sub-clinical mastitis. There was a tendency for TZD to have a higher globulin and lower BHBA compared to CTRL and a tendency for a higher increase in haptoglobin after IMI (TRTxTime P=0.06) with a quick recovery, indicating a stronger response of the liver to inflammation. No other parameters measured were affected by TZD treatment. Our findings indicate that addition of TZD has mild effect on inflammatory response in animals receiving adequate amount of vitamin A.

Keywords: immune response; mastitis; TZD