Graduate Thesis Or Dissertation
 

The NRF2-controlled Antioxidant Response, Alternative Forages, and Selenium supplementation for Improving Ruminant Productivity and Health

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  • Oxidative dysfunction can affect dairy animals during periods of heightened stress, particularly during the transition from pregnancy to lactation and during diseases, such as intramammary infection (IMI), and can contribute to increased inflammation, immune dysfunction, and cell death. As such, methods for ameliorating oxidative stress and restoring redox regulation may be important for improving ruminant health and productivity and are the focus of this dissertation. Central to the endogenous response to oxidative stress is the transcription factor NRF2; however, most experiments that have characterized this pathway have done so in nonruminant models. Presented in Chapter 2 are the results of a hybrid in vitro-in vivo investigation where the response of NRF2 to synthetic and natural modulators was analyzed in immortalized bovine mammary alveolar (MACT) cells using luciferase and cell viability assays. In that experiment, it was found that the NRF2 response in the bovine model was similar to what has been previously found in nonruminant studies, with the natural and synthetic NRF2 agonists stimulating NRF2 activity, while the natural antagonist of NRF2 inhibited its activity. Importantly, higher doses of both the agonists and antagonist induced higher degrees of cell toxicity; however, the response was significantly different when the treatments were done in traditional cell culture media compared to cow serum, a result that is partially attributed to higher levels of albumin present in the serum. The manuscript presented in Chapter 5 expands on the hybrid project by evaluating the effect that different pasture mixes, particularly those that are enriched with bioactive compounds, have on grazing dairy cow health and productivity, as well as the effect on NRF2 activity in vitro. While the forb and legume-based pastures were effective at improving antioxidant health, kidney and liver function, minimal effects on NRF2 activity were found using the hybrid model despite significant differences in phytochemicals, some potential NRF2-modulator, detected in the blood serum of cows grazed on those pastures. Provided the positive results on dairy cow health and antioxidant status in the grazing trial, two additional studies were performed to evaluate the effects of forb silages (chicory and plantain) in two different natural models of oxidative stress. Additionally, given the findings of previous studies that have highlighted the benefits of selenium supplementation on ruminant antioxidant health, the effects of selenium supplementation were also evaluated. In the manuscript presented in Chapter 7, chicory silage was fed to ewes during the four weeks before and four weeks after parturition, with some ewes also supplemented with selenium-yeast. In addition, one group of ewes, not fed chicory silage, were provided a one-time injection of inorganic selenium to evaluate the effects of the form of selenium supplementation. Overall, neither the type of silage nor selenium supplementation had a strong effect on ewe performance, with minor improvements in antioxidant status observed among ewes fed chicory silage. Continuing from the work presented in Chapter 7, the manuscript presented in Chapter 8 evaluated the effects of the same treatments on the response of some of the same ewes to intramammary infection. Importantly, plantain silage was included in the diets of ewes that had been previously fed chicory silage. In general, the type of silage and selenium supplementation had no effect on the response to intramammary infection. In summary, the work presented in this dissertation expands on previous work evaluating the antioxidant response in dairy ruminants, especially concerning NRF2, while also highlighting the difficulty of producing dramatic improvements in antioxidative response partially via NRF2 through diet-based approaches.
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  • Pending Publication
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  • 2023-02-22 to 2023-09-23

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