This review examines several molecular mechanisms underpinning oxidative stress in ruminants and their effects on blood and milk oxidative traits. We also investigate strategies to alleviate or repair oxidative damages by improving animal immune functions using novel feed additives. Microbial pathogenic cells, feeding management, and body condition score were some of the studied factors, inducing oxidative stress in ruminants. The predominance of Streptococcus spp. (24.22%), Acinetobacter spp. (21.37%), Romboutsia spp. (4.99%), Turicibacter spp., (2.64%), Stenotrophomonas spp. (2.33%), and Enterococcus spp. (1.86%) was found in the microbiome of mastitis cows with a decrease of d-mannose and increase of xanthine:guanine ratio when Streptococcus increased. Diversity of energy sources favoring the growth of Fusobacterium make it a keystone taxon contributing to metritis. Ruminal volatile fatty acids rose with high-concentrate diets that decreased the ruminal pH, causing a lysis of rumen microbes and release of endotoxins. Moreover, lipopolysaccharide (LPS) concentration, malondialdehyde (MDA), and superoxide dismutase (SOD) activities increased in high concentrate cows accompanied by a reduction of total antioxidant capacity (T-AOC), glutathione peroxidase (GPx), and catalase (CAT) activity. In addition, albumin and paraoxonase concentrations were inversely related to oxidative stress and contributed to the protection of low-density and high-density lipoproteins against lipid peroxidation, protein carbonyl, and lactoperoxidase. High concentrate diets increased the expression of MAPK pro-inflammatory genes and decreased the expression of antioxidant genes and proteins in mammary epithelial tissues. The expression levels of NrF2, NQO1, MT1E, UGT1A1, MGST3, and MT1A were downregulated, whereas NF-kB was upregulated with a high-grain or high concentrate diet. Amino-acids, vitamins, trace elements, and plant extracts have shown promising results through enhancing immune functions and repairing damaged cells exposed to oxidative stress. Further studies comparing the long-term effect of synthetic feed additives and natural plant additives on animal health and physiology remain to be investigated.

Heat stress (HS) is one of the most important factors posing harm to the economic wellbeing of dairy industries, as it reduces milk yield as well as milk protein content. Recent studies suggest that HS participates in the induction of tissue oxidative stress (OS), as elevated levels of reactive oxygen species (ROS) and mitochondrial dysfunction were observed in dairy cows exposed to hot conditions. The OS induced by HS likely contributes to the reduction in milk protein content, since insulin resistance and apoptosis are promoted by OS and are negatively associated with the synthesis of milk proteins. The apoptosis in the mammary gland directly decreases the amount of mammary epithelial cells, while the insulin resistance affects the regulation of insulin on mTOR pathways. To alleviate OS damages, strategies including antioxidants supplementation have been adopted, but caution needs to be applied as an inappropriate supplement with antioxidants can be harmful. Furthermore, the complete mechanisms by which HS induces OS and OS influences milk protein synthesis are still unclear and further investigation is needed.

Heat stress (HS) alters the rumen fermentation of dairy cows thereby affecting the metabolism of rumen papillae and thus the epithelial barrier function. The aim of the present study was to investigate if HS damages the barrier function of ruminal epithelia. Eight multiparous Holstein dairy cows with rumen cannula were randomly equally allocated to two replicates (n = 4), with each replicate being subjected to heat stress or thermal neutrality and pair-feeding in four environmental chambers. Micromorphological observation showed HS aggravated the shedding of the corneum and destroyed the physical barrier of the ruminal epithelium to a certain extent. Transcriptomics analysis of the rumen papillae revealed pathways associated with DNA replication and repair and amino acid metabolism were perturbated, the biological processes including sister chromatid segregation, etc. were up-regulated by HS, while the MAPK and NF-kB cell signaling pathways were downregulated. However, no heat stress-specific change in the expression of tight junction protein or TLR4 signaling was found, suggesting that HS negatively affected the physical barrier of the ruminal epithelium to some extent but did not break the ruminal epithelium. Heat stress invoked mechanisms to maintain the integrity of the rumen epithelial barrier by upregulating the expression of heat shock protein and repairments in rumen papillae. The increase in amino acid metabolism in rumen papillae might affect the nutrient utilization of the whole body. The findings of this study may inform future research to better understand how heat stress affects the physiology and productivity of lactating cows and the development of mitigation strategies.

Using animal manure as organic fertilizer to grow fodder crops is causing public health concerns because animal manure is the major reservoir of veterinary antibiotics. In this study, we used a mathematical model to estimate the risk of human exposure to veterinary antibiotics when using swine manure as organic fertilizer to grow alfalfa (Medicago sativa L.). Alfalfa was planted in a greenhouse and fertilized with swine manure spiked with oxytetracycline (OTC, at 0, 150, and 1500 mg/kg of manure), ofloxacin (OFL, at 0, 15, and 150 mg/kg), or sulfamonomethoxine (SMM, at 0, 5, 15 and 150 mg/kg). Alfalfa was harvested at the budding stage and ensiled for 60 days. Results showed that OTC and OFL could be detected in the alfalfa root, stem, and leaf with a concentration ranging from 8.85 to 59.17 μg OTC /kg and from 1.50 to 4.10 μg OFL/kg dry matter, but SMM could only be detected in the root ranging from 29.10 to 63.75 μg/kg dry matter. The ensiling for 60 days decreased the OFL concentration by 68.7% but only slightly decreased the OTC concentration. The maximum daily exposures of humans to OTC and OFL through liquid milk consumption were estimated to be 5.84E-8 and 1.63E-8 μg, respectively, both of which are well below the intake levels of OTC (72 μg) and OFL (54 μg) mandated by the European Union. The results of the present study indicate that using swine manure as organic fertilizer to grow alfalfa poses a limited risk for human exposure to veterinary antibiotics through the consumption of liquid milk.

Cooling can alleviate the negative consequences of heat stress on multiple milk production metrics in dairy cows. However, it is still controversial whether cooling can increase milk protein content compared with heat-stressed cows. The objective of the present study was to evaluate the relief effect of cooling on the decrease in milk protein concentration during heat stress and elucidate the potential metabolic mechanisms. Thirty lactating multiparous Holstein cows (days in milk = 175 ± 25 d, milk yield = 27.5 ± 2.5 kg/d; mean ± SD) were assigned to 1 of 3 treatments: heat stress (HS; n = 10), cooling (CL; n = 10), and cooling with pair-feeding (PFCL; n = 10). The barns for PFCL and CL cows were equipped with sprinklers and fans, whereas the barn for HS cows were not. The average temperature-humidity index during the experiment ranged from 74 to 83. The spraying was activated automatically 2 times per day (1130-1330 h and 1500-1600 h) with 3 min on and 6 min off during the first 2 wk, and 1.5 min on and 3 min off during the last 2 wk, whereas the fans operated 24 h/d. The experiment lasted for 4 wk in total. Milk, urine, feces, total mixed ration, blood, and rumen fluid samples were collected weekly. Compared with HS, feed efficiency (1.24 and 1.49), milk protein yield (0.82 and 0.94 kg/d), and milk fat yield (0.98 and 1.26 kg/d) were increased in PFCL, whereas the differences between CL and HS were not significant. Compared with HS cows, PFCL and CL cows had a lower respiratory rate (70.6, 59.1, and 60.3 breaths per minute, respectively), rectal temperature (38.95, 38.61, and 38.51°C), and shoulder skin temperature (33.95, 33.25, 33.40°C), and had greater milk protein content (3.41, 3.72, and 3.69%) and milk fat percent (4.08, 4.97, 4.65%). Both the blood activity of catalase (increased by 12.8 and 41.0%) and glutathione peroxidase (12.6 and 40.4%) of PFCL and CL cows were greater than the HS cows. Compared with HS, cooling increased the blood content of glucose, methionine, threonine, and cystathionine by 10.7% and 10.3%, 19.0% and 9.5%, 15.8% and 12.0%, and 9.5% and 23.8% in PFCL and CL, respectively. In conclusion, the results indicated that cooling partially rescued milk protein synthesis induced by heat stress, and the potential mechanism may have been due to increased antioxidant ability, blood glucose, and key AA. Consequently, in addition to modifying the environment, nutritional and physiological strategies designed to influence carbohydrate, AA, and oxidative homeostasis may be an opportunity to maintain or correct low milk protein content during the warm summer months.