An imbalance between proliferation and apoptosis is an important causal factor for disorders involving abnormal cell accumulation. Endothelin (ET)-1, a 21-amino-acid peptide with mitogenic and vasoconstricting activities, not only acts as a mitogen, but also attenuates paclitaxel-induced apoptosis in smooth muscle cells. In both human pericardial and prostatic smooth muscle cells, addition of ET-1 reduced paclitaxel-induced DNA fragmentation and phosphatidylserine on the cell surface, two characteristics of apoptosis. By comparison, angiotensin II, another vasoactive peptide, did not have a significant effect on apoptosis. The effect of ET-1 was dose-dependent with an EC50 of 1 nM. These results suggest that ET is a potential survival factor for smooth muscle cells, and that altered activity of the ET system in disease states has potential to contribute to aberrant cell growth.

Calves may experience increased oxidative stress at birth through activation of metabolic and respiratory processes. Reducing oxidative stress may enhance calf viability in early life. Our objective was to determine the dose response to fish and flaxseed oil when supplemented in colostrum on concentrations of plasma fatty acid (FA), FA metabolites, and index of oxidative stress during the critical first week of life in calves to understand how supplementing n-3 FA may decrease oxidative stress. We hypothesized that n-3 FA supplemented in colostrum in a linear dose-dependent fashion would associate with increased plasma n-3 FA concentrations and decreased oxidative stress. Twenty-four male and female Holstein calves were randomly assigned to receive 0, 30, 60, or 120 mL of a 1:1 fish to flaxseed oil supplement in colostrum. All calves received 2.8 L of previously frozen colostrum (≥22% Brix) with their respective treatment within 6 h after birth. Blood was sampled before first feeding after birth and on d 1, 2, 4, 7, and 14 d of age to assess oxidant status and plasma free PUFA, phospholipid FA, and oxylipid concentrations. Health indicators were observed daily. Indicators of general health and growth were unaffected by treatment. Supplemented calves exhibited greater concentrations of n-3 FA in plasma as free and phospholipid FA and some n-3 and n-6 FA-derived oxylipids in the first week of life in a linear fashion with increasing supplemental dose. Fish and flaxseed oil treatments did not alter oxidant status but overall decreased isoprostane concentrations in plasma, indicating oxidative stress was decreased. Together, these responses indicate that the fish and flaxseed oil supplement was antiinflammatory. In conclusion, supplementing colostrum with 30, 60, and 120 mL of a 1:1 mixture of fish and flaxseed oil linearly increased plasma concentrations of n-3 FA and metabolites and decreased biomarkers of oxidative stress, but did not alter oxidant status or affect health or growth. Our findings suggest neonatal calves may benefit from n-3 FA supplementation in colostrum to encourage a greater antiinflammatory state.

Our objective was to characterize the effects of supplementing newborn calves with n-3 fatty acids (FA) and α-tocopherol on blood lipid profiles and oxidant status in early life. Sixteen calves received 0 or 60 mL of 1:1 fish and flaxseed oil with 200 mg of α-tocopherol in 2.8 L of colostrum within 6 h after birth. Colostrum was >22% on the Brix scale. Blood was sampled on d 1, 2, 4, 7, 14, and 21 after birth for assessment of plasma polyunsaturated FA, α-tocopherol, total serum protein, and oxidant status index, an indirect indicator of oxidative stress that examines the balance between the concentration of reactive oxygen and nitrogen species and antioxidant capacity in serum. Health was observed daily. Weight and hip height were recorded at birth, 3 wk, and 8 wk. Data were analyzed with a Mixed procedure of SAS 9.4 (SAS Institute Inc., Cary, NC). Treatment did not alter concentration of total protein in blood serum, prevalence of diarrhea or other signs of disease, or rate of growth. Feeding n-3 FA and α-tocopherol increased plasma concentrations of the n-3 FA, including α-linolenic, eicosapentaenoic, and docosahexaenoic acids, with a concomitant decrease in oxidant status index during the first week of life. Concentrations of α-tocopherol decreased with supplementation, but all calves maintained adequate concentrations. Oxidant status index of treated calves returned to the level of control calves by d 14. We conclude that a colostrum supplement of n-3 FA and α-tocopherol is safe to administer to newborn calves, reduces oxidant status in the first week of life, and may improve health and performance.

Our objective was to supplement colostrum with n-3 fatty acids (FA) to provide anti-inflammatory mediators that may improve the immune response of neonatal calves. Elevated markers of inflammation have been associated with increased occurrence of calf disease in early life, thus decreasing animal productivity. We hypothesized that a colostrum supplement containing 60-mL of a 1:1 ratio fish: flaxseed oil blend with or without 200 mg of α-tocopherol might provide an advantageous start to early life by decreasing oxidative stress and regulating the inflammatory response. Calves were blocked by birth order and randomly assigned to 1 of 3 treatments: no supplement added to colostrum (control), 60 mL of 1:1 fish: flaxseed oil blend, and 60 mL of 1:1 fish: flaxseed oil blend with 200 mg of α-tocopherol. In total, 180 heifer calves (n = 60 per treatment) were enrolled on a commercial farm. After colostrum feeding, all calves were housed in individual hutches and fed milk replacer 3 times per day. Health was scored 3 times per week until weaning at 8 wk of age. Weight, wither height, and heart girth were measured after birth, 3 wk, and 8 wk of age to assess preweaning growth. A subgroup of 54 calves (18 blocks or 18 calves per treatment) were sampled 2 d (± 8 h) after birth to evaluate oxidant status, serum total protein, and inflammatory gene and cytokine protein expression in blood after an in vitro lipopolysaccharide (LPS) challenge as indicators of health and immunity. At 9 wk, calves were transported 18 h to another farm, and medical records were kept as an indicator of disease incidence up to 13 wk of age. Calf mortality was 1.8%, which is below industry average, and exceptional health scores were observed throughout the study. Health scores and growth were similar throughout the preweaning period regardless of treatment. Serum total protein indicated successful passive transfer in all calves, and oxidant status index was not affected by treatments on d 2 of age. Concentrations of tumor necrosis factor α increased with LPS stimulation, but the increase was not altered by treatment. Likewise, leukocyte gene expression of tumor necrosis factor α, IL-8 and IL-10, and cyclooxygenase-2 increased upon LPS stimulation, but the fold change did not differ with treatment. In conclusion, 60 mL of 1:1 ratio fish: flaxseed oil colostrum supplement did not enhance preweaning calf performance. Supplementing n-3 FA in a one-time meal may not provide the anti-inflammatory benefits observed with continuous feeding.

Study objectives were to evaluate the effects of replacing 40 mg/kg of dietary Zn from Zn sulfate (ZS) with Zn amino acid complex (ZA; Zinpro Corporation, Eden Prairie, MN) on inflammation and intestinal integrity in heat-stressed and pair-fed (PF) ruminants. Forty Holstein steers (173.6 ± 4.9 kg) were randomly assigned to 1 of 5 dietary-environmental treatments: ( 1) thermoneutral (TN) ad libitum with 75 mg/kg of dry matter (DM) ZS (ZSCON); (2) TN pair-fed with 75 mg/kg DM ZS (ZSPF); (3) TN pair-fed with 40 mg/ kg DM ZA and 35 mg/kg DM ZS (ZAPF); (4) heat stress (HS) ad libitum with 75 mg/kg DM ZS (ZSHS); and (5) HS ad libitum 40 mg/kg DM ZA and 35 mg/ kg DM ZS (ZAHS). Before study initiation, calves were fed their respective diets for 21 d. Following the pre-feeding phase, steers were transferred into environmental chambers and were subjected to 2 successive experimental periods. During period 1 (5 d), all steers were fed their respective diets ad libitum and housed in TN conditions (20.2 ± 1.4°C, 30.4 ± 4.3% relative humidity). During period 2 (6 d), ZSHS and ZAHS steers were exposed to cyclical HS conditions (27.1 ± 1.5°C to 35.0 ± 2.9°C, 19.3 ± 3.5% relative humidity), whereas the ZSCON, ZSPF, and ZAPF steers remained in TN conditions and were fed ad libitum or pair-fed relative to their ZSHS and ZAHS counterparts. Overall, steers exposed to HS had markedly increased rectal temperature (0.83°C), respiration rate (26 breaths per min), and skin temperature (8.00°C) relative to TN treatments. Rectal temperature from ZAHS steers was decreased (0.24°C) on d 4 to 6 of HS relative to ZSHS steers. Regardless of diet, HS decreased DMI (18%) relative to ZSCON steers. Circulating glucose from HS and PF steers decreased (16%) relative to ZSCON steers. Heat stress and nutrient restriction increased circulating nonesterified fatty acids 2-and 3-fold, respectively, compared with ZSCON steers. Serum amyloid A increased ~2-fold in PF relative to ZSCON and HS steers. We detected no treatment effect on blood pH; however, ZAHS steers had increased HCO 3 relative to ZSHS. Relative to ZSHS, ZAHS steers had increased jejunum villi height (25%), a tendency for increased ileum villi height (9%), and decreased duodenal villi width (16%). In summary, ZA supplementation has some beneficial effects on thermal indices, intestinal architecture characteristics, and biomarkers of leaky gut in heat-stressed steers, indicative of an ameliorated heat load, and thus may be a nutritional strategy to minimize negative consequences of HS.