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Journal of Dairy Science May 2022Previous research has shown that the brown seaweed Ascophyllum nodosum (ASCO) has antimicrobial and antioxidant properties and also increases milk I concentration. We...
Supplementation of Ascophyllum nodosum meal and monensin: Effects on diversity and relative abundance of ruminal bacterial taxa and the metabolism of iodine and arsenic in lactating dairy cows.
Previous research has shown that the brown seaweed Ascophyllum nodosum (ASCO) has antimicrobial and antioxidant properties and also increases milk I concentration. We aimed to investigate the effects of supplementing ASCO meal or monensin (MON) on ruminal fermentation, diversity and relative abundance of ruminal bacterial taxa, metabolism of I and As, and blood concentrations of thyroid hormones, antioxidant enzymes, and cortisol in lactating dairy cows. Five multiparous ruminally cannulated Jersey cows averaging (mean ± standard deviation) 102 ± 15 d in milk and 450 ± 33 kg of body weight at the beginning of the study were used in a Latin square design with 28-d periods (21 d for diet adaptation and 7 d for data and sample collection). Cows were fed ad libitum a basal diet containing (dry matter basis) 65% forage as haylage and corn silage and 35% concentrate and were randomly assigned to 1 of the following 5 dietary treatments: 0, 57, 113, or 170 g/d of ASCO meal, or 300 mg/d of MON. Supplements were placed directly into the rumen once daily after the morning feeding. Diets had no effect on ruminal pH and NH-N concentration, which averaged 6.02 and 6.86 mg/dL, respectively. Total volatile fatty acid concentration decreased linearly in cows fed incremental amounts of ASCO meal. Supplementation with ASCO meal did not change the ruminal molar proportions of volatile fatty acids apart from butyrate, which responded quadratically with the lowest values observed at 56 and 113 g/d of ASCO supplementation. Compared with the control diet or diets containing ASCO meal, cows fed MON showed greater molar proportion of propionate. Diets did not affect the α diversity indices Shannon, Simpson, and Fisher for ruminal bacteria. However, feeding incremental levels of ASCO meal linearly decreased the relative abundance of Tenericutes in ruminal fluid. Monensin increased the relative abundance of the CAG:352 bacterial genus in ruminal fluid compared with the control diet. Linear increases in response to ASCO meal supplementation were observed for the concentrations and output of I in serum, milk, urine, and feces. Fecal excretion of As increased linearly in cows fed varying amounts of ASCO meal, but ASCO did not affect the concentration and secretion of As in milk. The plasma activities of the antioxidant enzymes and the serum concentrations of thyroid hormones did not change. In contrast, circulating cortisol decreased linearly in diets containing ASCO meal. The apparent total-tract digestibilities of dry matter, organic matter, and crude protein increased linearly with ASCO meal, but those of neutral and acid detergent fiber were not affected. In summary, feeding incremental amounts of ASCO meal decreased serum cortisol concentration, and increased I concentrations and output in serum, milk, feces, and urine.
Topics: Animals; Antioxidants; Arsenic; Ascophyllum; Bacteria; Cattle; Dietary Supplements; Digestion; Fatty Acids, Volatile; Female; Hydrocortisone; Iodine; Lactation; Monensin; Rumen
PubMed: 35221070
DOI: 10.3168/jds.2021-21107 -
Annals of Medicine Dec 2023Colorectal cancer is the third leading cause of death in patients with cancers in America. Monensin has represented anti-cancer effect on various human cancer cells. We...
BACKGROUND/AIMS
Colorectal cancer is the third leading cause of death in patients with cancers in America. Monensin has represented anti-cancer effect on various human cancer cells. We seek to investigate the effect of monensin on proliferation of human colorectal cancer cells and explore whether IGF1R signaling pathway is involved in anti-cancer mechanism of monensin.
METHODS
Cell proliferation and migration were assessed by crystal violet staining and cell wounding assay respectively. Cell apoptosis was analyzed by Hoechst 33258 staining and flow cytometry. Cell cycle progression was detected with the use of flow cytometry. Cancer-associated pathways were assessed with the use of pathway-specific reporters. Gene expression was detected by touchdown-quantitative real-time PCR. Inhibition of IGF1R was tested by immunofluorescence staining. Inhibition of IGF1R signaling was accomplished by adenovirus-mediated expression of IGF1.
RESULTS
We found that monensin not only effectively inhibited cell proliferation, cell migration as well as cell cycle progression, but also induced apoptosis and G1 arrest in human colorectal cancer cells. Monensin was shown to target multiple cancer-related signaling pathways such as Elk1, AP1, as well as Myc/max, and suppressed IGF1R expression increasing IGF1 in colorectal cancer cells.
CONCLUSION
Monensin could suppressed IGF1R expression increasing IGF1 in colorectal cancer cells. It has the potential to be repurposed as an anti-colorectal cancer agent, but further studies are still required to investigate the detailed mechanisms of monensin underlying its anti-cancer motion.Key MessagesMonensin inhibits the cell proliferation and the migration, induces apoptosis and inhibits cell cycle progression in human colorectal cancer cells.Monensin may exert anti-cancer activity by targeting multiple signaling pathways, including the IGF1R signaling pathway.Monensin has the potential to be repurposed as an anti-colorectal cancer agent.
Topics: Humans; Anti-Bacterial Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Monensin; Neoplasms; Receptor, IGF Type 1; Signal Transduction; Colorectal Neoplasms
PubMed: 36896461
DOI: 10.1080/07853890.2023.2166980 -
Journal of Dairy Science Aug 2013Monensin is a widely used feed additive with the potential to minimize methane (CH4) emissions from cattle. Several studies have investigated the effects of monensin on... (Meta-Analysis)
Meta-Analysis
Monensin is a widely used feed additive with the potential to minimize methane (CH4) emissions from cattle. Several studies have investigated the effects of monensin on CH4, but findings have been inconsistent. The objective of the present study was to conduct meta-analyses to quantitatively summarize the effect of monensin on CH4 production (g/d) and the percentage of dietary gross energy lost as CH4 (Ym) in dairy cows and beef steers. Data from 22 controlled studies were used. Heterogeneity of the monensin effects were estimated using random effect models. Due to significant heterogeneity (>68%) in both dairy and beef studies, the random effect models were then extended to mixed effect models by including fixed effects of DMI, dietary nutrient contents, monensin dose, and length of monensin treatment period. Monensin reduced Ym from 5.97 to 5.43% and diets with greater neutral detergent fiber contents (g/kg of dry matter) tended to enhance the monensin effect on CH4 in beef steers. When adjusted for the neutral detergent fiber effect, monensin supplementation [average 32 mg/kg of dry matter intake (DMI)] reduced CH4 emissions from beef steers by 19±4 g/d. Dietary ether extract content and DMI had a positive and a negative effect on monensin in dairy cows, respectively. When adjusted for these 2 effects in the final mixed-effect model, monensin feeding (average 21 mg/kg of DMI) was associated with a 6±3 g/d reduction in CH4 emissions in dairy cows. When analyzed across dairy and beef cattle studies, DMI or monensin dose (mg/kg of DMI) tended to decrease or increase the effect of monensin in reducing methane emissions, respectively. Methane mitigation effects of monensin in dairy cows (-12±6 g/d) and beef steers (-14±6 g/d) became similar when adjusted for the monensin dose differences between dairy cow and beef steer studies. When adjusted for DMI differences, monensin reduced Ym in dairy cows (-0.23±0.14) and beef steers (-0.33±0.16). Monensin treatment period length did not significantly modify the monensin effects in dairy cow or beef steer studies. Overall, monensin had stronger antimethanogenic effects in beef steers than dairy cows, but the effects in dairy cows could potentially be improved by dietary composition modifications and increasing the monensin dose.
Topics: Animals; Cattle; Female; Male; Methane; Monensin
PubMed: 23769353
DOI: 10.3168/jds.2012-5923 -
BMC Veterinary Research Jan 2018Acute ruminal lactic acidosis (ARLA) is a major nutritional and metabolic disorder usually characterized by excessive or non-adapted intake of diets rich in... (Comparative Study)
Comparative Study
BACKGROUND
Acute ruminal lactic acidosis (ARLA) is a major nutritional and metabolic disorder usually characterized by excessive or non-adapted intake of diets rich in nonstructural carbohydrates. Feed additives that regulate the ruminal environment have been used to prevent ARLA, such as ionophores and, more recently, yeast culture. Thus, we aimed to compare the efficacy of a yeast-based culture (Saccharomyces cerevisiae) with that of monensin sodium in the prevention of ARLA in sheep. Eighteen male, crossbred, rumen-cannulated sheep were randomly distributed into three groups of six animals: control, yeast culture and monensin. Thirty days after the start of supplementation with yeast culture (4 × 10 cfu/animal/day of S. cerevisiae) and monensin (33 mg/kg of total dry matter intake), 15 g/kg BW of sucrose was administered directly into the rumen of the animals to induce ARLA. Samples of blood and ruminal fluid were collected at the following time points: at baseline (T0 h) immediately before the induction of ARLA; 6 h (T6 h); 12 h (T12 h); 18 h (T18 h); 24 h (T24 h); 36 h (T36 h); and 48 h (T48 h) after ARLA induction.
RESULTS
Ruminal pH was higher in monensin group at T12 h and in yeast culture group at T36 h when compared to control group. Lower values of L-Lactate were found at yeast culture group at T24 h and T36 h. Monensin showed prophylactic effect by decreasing the rate of ruminal pH decline and occasionally reducing ruminal acidosis, whereas probiotics resulted in less accumulation of lactic acid in the rumen and a lower degree of systemic acidosis.
CONCLUSION
The use of yeast culture can be beneficial in the prevention and treatment of ARLA in sheep, because it can effectively reduce the accumulation of lactic acid, and thereby increase ruminal pH and reduce ruminal osmolarity. On the other hand, monensin showed prophylactic effect by decreasing the rate of ruminal pH decline and occasionally reducing ruminal acidosis, however, it did not directly prevent these conditions.
Topics: Acidosis, Lactic; Animals; Hydrogen-Ion Concentration; Male; Monensin; Probiotics; Rumen; Saccharomyces cerevisiae; Sheep; Sheep Diseases; Sucrose
PubMed: 29316923
DOI: 10.1186/s12917-017-1264-4 -
Scientific Reports Feb 2019Epithelial-to-mesenchymal transition (EMT) is implicated in cancer metastasis and drug resistance. Specifically targeting cancer cells in an EMT-like state may have...
Epithelial-to-mesenchymal transition (EMT) is implicated in cancer metastasis and drug resistance. Specifically targeting cancer cells in an EMT-like state may have therapeutic value. In this study, we developed a cell imaging-based high-content screening protocol to identify EMT-selective cytotoxic compounds. Among the 2,640 compounds tested, salinomycin and monensin, both monovalent cation ionophores, displayed a potent and selective cytotoxic effect against EMT-like cells. The mechanism of action of monensin was further evaluated. Monensin (10 nM) induced apoptosis, cell cycle arrest, and an increase in reactive oxygen species (ROS) production in TEM 4-18 cells. In addition, monensin rapidly induced swelling of Golgi apparatus and perturbed mitochondrial function. These are previously known effects of monensin, albeit occurring at much higher concentrations in the micromolar range. The cytotoxic effect of monensin was not blocked by inhibitors of ferroptosis. To explore the generality of our findings, we evaluated the toxicity of monensin in 24 human cancer cell lines and classified them as resistant or sensitive based on IC cutoff of 100 nM. Gene Set Enrichment Analysis identified EMT as the top enriched gene set in the sensitive group. Importantly, increased monensin sensitivity in EMT-like cells is associated with elevated uptake of H-monensin compared to resistant cells.
Topics: Apoptosis; Biological Transport; Cell Cycle Checkpoints; Cell Line; Drug Evaluation, Preclinical; Epithelial-Mesenchymal Transition; Golgi Apparatus; Humans; Mitochondria; Molecular Imaging; Monensin; Reactive Oxygen Species
PubMed: 30718715
DOI: 10.1038/s41598-018-38019-y -
Poultry Science Jan 1999The efficacy of different concentrations of monensin in turkeys exposed to field isolates of Eimeria and the effect of the withdrawal of monensin from their diet were...
The efficacy of different concentrations of monensin in turkeys exposed to field isolates of Eimeria and the effect of the withdrawal of monensin from their diet were investigated. Results of a battery study indicated that 66 ppm monensin was effective against three species of Eimeria in the turkey. In floor pens in which poults were exposed to infection, use of 59.5, 79.4, and 99.2 ppm monensin resulted in reduced mortality and improved feed conversion at 3 wk of age compared with birds that had received no medication. Poults given 59.5 ppm monensin weighed more and had a better feed conversion at 3 wk than poults given 79.4 or 99.2 ppm monensin, but at 10 wk no differences in the body weight or feed conversion of poults given different concentrations of drug were apparent. At 14 wk (and from 10 to 14 wk), poults that had been given 99.2 ppm monensin had a lower feed intake and weighed less than birds that had been given 59.5 ppm of the drug but there were no significant differences in feed conversion. There was no significant difference in the weight gain or feed conversion of poults from 10 to 14 wk of age whether monensin was present in the feed or had been withdrawn. No evidence of compensatory growth was found in the present study.
Topics: Animals; Coccidiosis; Coccidiostats; Eimeria; Feces; Monensin; Parasite Egg Count; Poultry Diseases; Turkeys
PubMed: 10023746
DOI: 10.1093/ps/78.1.50 -
Molecules (Basel, Switzerland) Dec 2019Lincomycin, monensin, and roxarsone are commonly used veterinary drugs. This study investigated their behaviours in different soils and their toxic effects on...
Lincomycin, monensin, and roxarsone are commonly used veterinary drugs. This study investigated their behaviours in different soils and their toxic effects on environmental organisms. Sorption and mobility analyses were performed to detect the migration capacity of drugs in soils. Toxic effects were evaluated by inhibition or acute toxicity tests on six organism species: algae, plants, daphnia, fish, earthworms and quails. The log K values (Freundlich model) of drugs were: lincomycin in laterite soil was 1.82; monensin in laterite soil was 2.76; and roxarsone in black soil was 1.29. The R value of lincomycin, roxarsone, monensin were 0.4995, 0.4493 and 0.8348 in laterite soil, and 0.5258, 0.5835 and 0.8033 in black soil, respectively. The EC for , , and LC/LD for , , and Coturnix coturnix were: 13.15 mg/L,32.18 mg/kg dry soil,292.6 mg/L,452.7 mg/L,5.74 g/kg dry soil and 103.9 mg/kg (roxarsone); 1.085 mg/L, 25 mg/kg dry soil, 21.1 mg/L, 4.76 mg/L, 0.346 g/kg dry soil and 672.8 mg/kg (monensin); 0.813 mg/L, 35.40 mg/kg dry soil, >400 mg/L, >2800 mg/L, >15 g/kg dry soil, >2000 mg/kg (lincomycin). These results showed that the environmental effects of veterinary drug residues should not be neglected, due to their mobility in environmental media and potential toxic effects on environmental organisms.
Topics: Animals; Arabidopsis; Coturnix; Daphnia; Lincomycin; Monensin; Oligochaeta; Roxarsone; Scenedesmus; Zebrafish
PubMed: 31817501
DOI: 10.3390/molecules24244465 -
Applied and Environmental Microbiology May 1992New strains with enhanced resistance to monensin were developed from Prevotella (Bacteroides) ruminicola subsp. ruminicola 23 and P. ruminicola subsp. brevis GA33 by...
New strains with enhanced resistance to monensin were developed from Prevotella (Bacteroides) ruminicola subsp. ruminicola 23 and P. ruminicola subsp. brevis GA33 by stepwise exposure to increasing concentrations of monensin. The resulting resistant strains (23MR2 and GA33MR) could initiate growth in concentrations of monensin which were 4 to 40 times greater than those which inhibited the parental strains. Resistant strains also showed enhanced resistance to nigericin and combinations of monensin and nigericin but retained sensitivity to lasalocid. Glucose utilization in cultures of the monensin-sensitive strains (23 and GA33) and one monensin-resistant strain (23MR2) was retarded but not completely inhibited when logarithmic cultures were challenged with monensin (10 mg/liter). Monensin challenge of cultures of the two monensin-sensitive strains (23 and GA33) was characterized by 78 and 51% decreases in protein yield (milligrams of protein per mole of glucose utilized), respectively. Protein yields in cultures of resistant strain 23MR2 were decreased by only 21% following monensin challenge. Cell yields and rates of glucose utilization by resistant strains GA33MR were not decreased by challenge with 10 mg of monensin per liter. Resistant strains produced greater relative proportions of propionate and less acetate than the corresponding sensitive strains. The relative amounts of succinate produced were greater in cultures of strains 23, GA33, and 23MR2 following monensin challenge. However, only minor changes in end product formation were associate with monensin challenge of resistant strain GA33MR. These results suggest that monensin has significant effects on both the growth characteristics and metabolic activities of these predominant, gram-negative ruminal bacteria.
Topics: Bacterial Proteins; Bacteroides; Drug Resistance, Microbial; Glucose; Ionophores; Kinetics; Microbial Sensitivity Tests; Monensin; Species Specificity
PubMed: 1622231
DOI: 10.1128/aem.58.5.1617-1623.1992 -
Nature Communications Jan 2020The Golgi is a dynamic organelle whose correct assembly is crucial for cellular homeostasis. Perturbations in Golgi structure are associated with numerous disorders from...
The Golgi is a dynamic organelle whose correct assembly is crucial for cellular homeostasis. Perturbations in Golgi structure are associated with numerous disorders from neurodegeneration to cancer. However, whether and how dispersal of the Golgi apparatus is actively regulated under stress, and the consequences of Golgi dispersal, remain unknown. Here we demonstrate that 26S proteasomes are associated with the cytosolic surface of Golgi membranes to facilitate Golgi Apparatus-Related Degradation (GARD) and degradation of GM130 in response to Golgi stress. The degradation of GM130 is dependent on p97/VCP and 26S proteasomes, and required for Golgi dispersal. Finally, we show that perturbation of Golgi homeostasis induces cell death of multiple myeloma in vitro and in vivo, offering a therapeutic strategy for this malignancy. Taken together, this work reveals a mechanism of Golgi-localized proteasomal degradation, providing a functional link between proteostasis control and Golgi architecture, which may be critical in various secretion-related pathologies.
Topics: Animals; Apoptosis; Autoantigens; Cell Line, Tumor; Disease Models, Animal; Golgi Apparatus; HEK293 Cells; Humans; Intracellular Membranes; Ionophores; Membrane Proteins; Mice; Monensin; Multiple Myeloma; Proteasome Endopeptidase Complex; Proteolysis; Proteostasis; Ubiquitination; Valosin Containing Protein
PubMed: 31964869
DOI: 10.1038/s41467-019-14038-9 -
Journal of Dairy Science Oct 2022Controversy has existed as to whether monensin will provide equal or differential benefits in a higher-energy, lower-roughage close-up diet versus a higher-roughage,...
Controversy has existed as to whether monensin will provide equal or differential benefits in a higher-energy, lower-roughage close-up diet versus a higher-roughage, lower-energy diet. Our objective was to determine the rumen effects of a controlled-energy, high-fiber diet balanced to meet but not greatly exceed energy requirements during the dry period or a traditional 2-group approach of higher-energy close-up diet. The effects of added monensin in each diet type were determined. Multiparous Holstein cows (n = 17) were fitted surgically with ruminal cannulas. During the first 4 wk of the dry period, all cows were fed a controlled-energy, high-fiber diet (CE) as a total mixed ration for ad libitum intake. During the last 3 wk before calving, half of the cows were switched to a higher-energy, close-up diet until calving (CU), whereas the other half continued to receive the CE diet. Within each dietary group, half of the cows received monensin (MON) supplementation in the diet (24.2 g/t of total dry matter) and half did not (CON). After calving, all cows received the same lactation diet containing monensin (15.4 g/t of dietary dry matter). At 14 d prepartum, dry matter intake was not different across treatments. The weight of rumen contents was greater for cows fed CE. Rumen liquid dilution rate, solids passage rate, pH, total volatile fatty acid (VFA) concentrations, molar proportions of acetate and propionate, and papillae length did not differ among diets. Butyrate percentage tended to be greater for cows fed CE. Postpartum, dry matter intake, mass of rumen contents, solids passage rate, pH, total VFA concentration, molar percentages of propionate and butyrate, and papillae length did not differ among treatments. Liquid dilution rate (16.6, 10.7, 16.0, and 18.2%/h for CE + CON, CE + MON, CU + CON, and CU + MON, respectively) was affected by a diet × monensin interaction. Cows on the CE + CON diet had a greater ruminal proportion of acetate than did cows fed CU + CON, whereas cows fed monensin on either diet were intermediate (diet × monensin interaction). Addition of MON to the CU diet decreased the proportion of propionate (diet × monensin interaction). Cows fed CE had greater mass of rumen contents before parturtition but the high inclusion of wheat straw in the CE diet did not negatively affect rumen papillae length. Monensin inclusion differentially affected liquid passage rate and VFA concentrations.
Topics: Animals; Cattle; Female; Butyrates; Diet; Dietary Fiber; Monensin; Propionates; Rumen
PubMed: 35965123
DOI: 10.3168/jds.2022-21917