ethyl-cellulose and Inflammation

Enhancing the supply of rumen-protected Met (RPM) during the peripartum period alleviates inflammation and oxidative stress status in dairy cows. We tested the hypothesis that RPM could increase abundance of genes and proteins related to glutathione (GSH) metabolism and the antioxidant transcription factor nuclear factor erythroid 2-like 2 (NFE2L2) in subcutaneous adipose tissue. Multiparous Holstein cows were fed a basal diet [control prepartum diet = 1.47 Mcal/kg of dry matter (DM) and 15.3% crude protein; control postpartum diet = 1.67 Mcal/kg of DM and 17.7% crude protein] or the control plus ethyl-cellulose RPM at a rate of 0.09 and 0.10% of DM intake before expected calving and after calving, respectively. Sixty cows were assigned to treatments based on parity, previous 305-d milk yield, and body condition score at 28 d from parturition. Diets were fed from -28 to 30 d. Biopsies of subcutaneous adipose tissue collected on d -10, 10, and 30 relative to parturition from 7 cows in each group were used for measuring concentrations of GSH, reactive oxygen species, superoxide dismutase, malondialdehyde, and mRNA and protein abundance (Western blotting). A repeated-measures ANOVA was used for statistics. The statistical model included the random effect of block and fixed effects of treatment, time, and its interaction. There was a diet × time effect for reactive oxygen species due to lower concentrations in Met versus control cows specifically at d -10. Cows fed Met also had lower concentrations of malondialdehyde in subcutaneous adipose tissue. Compared with controls, overall mRNA abundance of the GSH metabolism-related genes cystathionine-β-synthase (CBS), glutamate-cysteine ligase modifier subunit (GCLM), glutathione reductase (GSR), and glutathione peroxidase 1 (GPX1) was greater in cows fed Met. Furthermore, supply of Met resulted in an overall upregulation of protein abundance of glutathione peroxidase (GPX) 1, GPX3, glutathione S-transferase mu 1 (GSTM1), and glutathione S-transferase α 4 (GSTA4), all related to GSH metabolism. There was a diet × time effect for protein abundance of NFE2L2 and its repressor Kelch-like ECH associated protein 1 (KEAP1) due to lower values at 30 d in cows fed Met versus controls. The abundance of phosphorylated NFE2L2 was lower at 30 d in response to Met. Overall, the data suggest that exogenous Met may play a role in activating GSH metabolism and the antioxidant NFE2L2 pathways in subcutaneous adipose tissue.

Topics: Adipose Tissue; Animals; Antioxidants; Cattle; Cellulose; Diet; Dietary Supplements; Female; Glutathione; Inflammation; Kelch-Like ECH-Associated Protein 1; Methionine; Milk; NF-E2-Related Factor 2; Oxidative Stress; Peripartum Period; Phosphorylation; Postpartum Period; Pregnancy; Reactive Oxygen Species; Rumen

The periparturient period is the most critical phase in the productive cycle of dairy cows and is characterized by impairment of the immune system. Our objective was to evaluate the effect of feeding ethyl-cellulose rumen-protected methionine (RPM) starting at d -28 from expected parturition through 60 d in milk on biomarkers of inflammation, oxidative stress, and liver function as well as leukocyte function. Sixty multiparous Holstein cows were used in a block design and assigned to either a control or the control plus ethyl-cellulose RPM (Mepron, Evonik Nutrition & Care GmbH). Mepron was supplied from -28 to 60 d in milk at a rate of 0.09% and 0.10% dry matter during the prepartum and postpartum period. That rate ensured that the ratio of Lys to Met in the metabolizable protein was close to 2.8:1. Blood samples from 15 clinically healthy cows per treatment were collected at d -30, -14, 1, 7, 21, 30, and 60 and analyzed for biomarkers of liver function, inflammation, and oxidative stress. Neutrophil and monocyte function in whole blood was measured in vitro at -14, 1, 7, 21, and 30 d in milk. The statistical model included the random effect of block and fixed effect of treatment, time, and its interaction. Compared with control, ethyl-cellulose RPM increased plasma cholesterol and paraoxonase after parturition. Among the inflammation biomarkers measured, ethyl-cellulose RPM led to greater albumin (negative acute-phase protein) and lower haptoglobin than control cows. Although concentration of IL-1β was not affected by treatments, greater IL-6 concentration was detected in response to ethyl-cellulose RPM. Cows supplemented with ethyl-cellulose RPM had greater plasma concentration of ferric-reducing antioxidant power, β-carotene, tocopherol, and total and reduced glutathione, whereas reactive oxygen metabolites were lower compared with control cows. Compared with control, ethyl-cellulose RPM enhanced neutrophil phagocytosis and oxidative burst. Overall, the results indicate that ethyl-cellulose RPM supply to obtain a Lys-to-Met ratio of 2.8:1 in the metabolizable protein during the periparturient period and early lactation is an effective approach to help mitigate oxidative stress and inflammation as well as enhance liver and neutrophil function in dairy cows.

Topics: Animals; Antioxidants; Biomarkers; Cattle; Cellulose; Dietary Supplements; Female; Inflammation; Lactation; Liver; Methionine; Milk; Models, Statistical; Neutrophils; Oxidative Stress; Peripartum Period; Pregnancy; Rumen