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Journal of Animal Science Dec 2022This study aimed to determine the viability of sporozoites from Eimeria bovis when exposed to sodium butyrate (SB), monensin (MON), or butyric acid (BA), and to...
Short Communication: effect of sodium butyrate, monensin, and butyric acid on the viability of Eimeria bovis sporozoites and their degree of damage to a bovine epithelial cell line.
This study aimed to determine the viability of sporozoites from Eimeria bovis when exposed to sodium butyrate (SB), monensin (MON), or butyric acid (BA), and to determine the effects of SB on sporozoite invasion of cells in comparison to MON as measured by the damage to a bovine epithelial cell line. To determine viability, isolated sporozoites were suspended in one of four treatments: control (CON) of cell culture medium alone, SB = 0.028 mg/mL suspended in control medium, MON = 0.01 mg/mL suspended in CON, and BA = 0.18 mg/mL suspended in CON. The number of live sporozoites was less for the MON and BA treatments compared to the CON and SB treatments. The number of dead sporozoites was similar regardless of treatment. There was a trend for treatment to affect the percent sporozoite viability. Control, SB and BA treatments were similar, while MON compared to control and SB had decreased percent viability. Results for MON, when compared to BA, were similar for percent viability. Lactate dehydrogenase (LDH) release was used to determine cellular damage to Madin Darby Bovine Kidney (MDBK) cells when exposed to E. bovis sporozoites in vitro. Cells were exposed to similar numbers of sporozoites and treated with: CON, SB = 0.028 mg/mL in control medium, MON = 0.01 mg/mL in control medium. Control LDH result (with sporozoites) was greater than both the SB and MON treatments while the LDH for SB and Mon and cells not exposed to sporozoites were similar. SB and MON were both shown to decrease cellular damage to MDBK cells as determined by decreased LDH release. SB has the potential to act as an anticoccidial alternative to MON.
Topics: Cattle; Animals; Eimeria; Monensin; Butyric Acid; Sporozoites; Epithelial Cells
PubMed: 36315476
DOI: 10.1093/jas/skac360 -
Poultry Science Sep 2010In July 1971, the polyether ionophorous antibiotic monensin was introduced in the United States for the control of coccidiosis in poultry. At that time, prospects for... (Review)
Review
In July 1971, the polyether ionophorous antibiotic monensin was introduced in the United States for the control of coccidiosis in poultry. At that time, prospects for new anticoccidial agents were not good. Amprolium had enjoyed several years of use, but many other compounds had been abandoned as resistance to them developed. After the introduction of monensin, most commercial broilers were medicated with the drug and it is still widely used for this purpose today. Apart from in poultry, monensin is also used to control coccidiosis in game birds, sheep, and cattle. Indeed, more animals have been medicated with ionophores, such as monensin, for control of disease than any other medicinal agents in the history of veterinary medicine. In this review, we discuss the discovery, mode of action, and efficacy of monensin, together with matters of importance to the poultry industry such as commercial use, drug resistance, toxicity, pharmacology and residues, host immunity to coccidiosis, and effects in other avian species.
Topics: Animals; Coccidiosis; Coccidiostats; Drug Resistance; Monensin; Poultry; Poultry Diseases
PubMed: 20709963
DOI: 10.3382/ps.2010-00931 -
Toxins Jun 2022Carboxylic ionophores, such as monensin, salinomycin and lasalocid, are polyether antibiotics used widely in production animals for the control of coccidiosis, as well...
Carboxylic ionophores, such as monensin, salinomycin and lasalocid, are polyether antibiotics used widely in production animals for the control of coccidiosis, as well as for the promotion of growth and feed efficiency. Although the benefits of using ionophores are undisputed, cases of ionophore toxicosis do occur, primarily targeting the cardiac and skeletal muscles of affected animals. The 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide (MTT) viability assay was used to determine the cytotoxicity of monensin, salinomycin and lasalocid on mouse skeletal myoblasts (C2C12). Immunocytochemistry and immunofluorescent techniques were, in turn, performed to investigate the effects of the ionophores on the microfilament, microtubule and intermediate filament, i.e., desmin and synemin networks of the myoblasts. Monensin was the most cytotoxic of the three ionophores, followed by salinomycin and finally lasalocid. Monensin and salinomycin exposure resulted in the aggregation of desmin around the nuclei of affected myoblasts. The synemin, microtubule and microfilament networks were less affected; however, vesicles throughout the myoblast's cytoplasm produced gaps within the microtubule and, to a limited extent, the synemin and microfilament networks. In conclusion, ionophore exposure disrupted desmin filaments, which could contribute to the myofibrillar degeneration and necrosis seen in the skeletal muscles of animals suffering from ionophore toxicosis.
Topics: Animals; Cytoskeletal Proteins; Desmin; Ionophores; Lasalocid; Mice; Monensin; Myoblasts; Pyrans
PubMed: 35878184
DOI: 10.3390/toxins14070447 -
Biochimica Et Biophysica Acta May 1990Monensin, a monovalent ion-selective ionophore, facilitates the transmembrane exchange of principally sodium ions for protons. The outer surface of the ionophore-ion... (Review)
Review
Monensin, a monovalent ion-selective ionophore, facilitates the transmembrane exchange of principally sodium ions for protons. The outer surface of the ionophore-ion complex is composed largely of nonpolar hydrocarbon, which imparts a high solubility to the complexes in nonpolar solvents. In biological systems, these complexes are freely soluble in the lipid components of membranes and, presumably, diffuse or shuttle through the membranes from one aqueous membrane interface to the other. The net effect for monensin is a trans-membrane exchange of sodium ions for protons. However, the interaction of an ionophore with biological membranes, and its ionophoric expression, is highly dependent on the biochemical configuration of the membrane itself. One apparent consequence of this exchange is the neutralization of acidic intracellular compartments such as the trans Golgi apparatus cisternae and associated elements, lysosomes, and certain endosomes. This is accompanied by a disruption of trans Golgi apparatus cisternae and of lysosome and acidic endosome function. At the same time, Golgi apparatus cisternae appear to swell, presumably due to osmotic uptake of water resulting from the inward movement of ions. Monensin effects on Golgi apparatus are observed in cells from a wide range of plant and animal species. The action of monensin is most often exerted on the trans half of the stacked cisternae, often near the point of exit of secretory vesicles at the trans face of the stacked cisternae, or, especially at low monensin concentrations or short exposure times, near the middle of the stacked cisternae. The effects of monensin are quite rapid in both animal and plant cells; i.e., changes in Golgi apparatus may be observed after only 2-5 min of exposure. It is implicit in these observations that the uptake of osmotically active cations is accompanied by a concomitant efflux of H+ and that a net influx of protons would be required to sustain the ionic exchange long enough to account for the swelling of cisternae observed in electron micrographs. In the Golgi apparatus, late processing events such as terminal glycosylation and proteolytic cleavages are most susceptible to inhibition by monensin. Yet, many incompletely processed molecules may still be secreted via yet poorly understood mechanisms that appear to bypass the Golgi apparatus. In endocytosis, monensin does not prevent internalization. However, intracellular degradation of internalized ligands may be prevented.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Animals; Biological Transport; Endocytosis; Exocytosis; Golgi Apparatus; Humans; Monensin; Potassium; Protons; Sodium
PubMed: 2160275
DOI: 10.1016/0304-4157(90)90008-z -
Applied and Environmental Microbiology Jul 1983Total and monensin-resistant anaerobic bacterial populations and volatile fatty acid concentrations were examined in the rumens of steers fed monensin-containing (33...
Total and monensin-resistant anaerobic bacterial populations and volatile fatty acid concentrations were examined in the rumens of steers fed monensin-containing (33 mg/kg) and unmedicated diets. Total anaerobic counts on a habitat-simulating medium ranged from 7.1 X 10(8) to 7.1 X 10(9) CFU/g of rumen ingesta and were not significantly different in animals fed the two diets. The mean percentage of the anaerobic population resistant to monensin (10 micrograms/ml) was significantly greater in animals receiving the monensin-supplemented diet for 33 days than in those receiving the unmedicated diet (63.6 and 32.8%, respectively). Treatment group differences in monensin resistance tended to develop later than characteristic differences in acetate/propionate ratios. Relative proportions of resistant organisms in monensin-fed animals remained significantly greater for at least 18 days after monensin was deleted from the ration, whereas acetate/propionate ratios increased to values comparable to those in the control within 10 days. These data suggest that monensin-resistant bacteria may be present in greater numbers in the rumens of animals fed monensin-supplemented diets. However, greater proportions of monensin-resistant organisms were not necessarily associated with altered fermentation patterns.
Topics: Anaerobiosis; Animals; Bacteria; Cattle; Diet; Drug Resistance, Microbial; Fatty Acids, Volatile; Female; Furans; Monensin; Rumen
PubMed: 6614902
DOI: 10.1128/aem.46.1.160-164.1983 -
Clinical and Translational Science Sep 2023Monensin is an ionophore antibiotic that inhibits the growth of cancer cells. The aim of this study was to investigate the apoptosis-mediated anticarcinogenic effects of...
Monensin is an ionophore antibiotic that inhibits the growth of cancer cells. The aim of this study was to investigate the apoptosis-mediated anticarcinogenic effects of monensin in SH-SY5Y neuroblastoma cells. The effects of monensin on cell viability, invasion, migration, and colony formation were determined by XTT, matrigel-chamber, wound healing, and colony formation tests, respectively. The effects of monensin on apoptosis were determined by real-time polymerase chain reaction, TUNEL, Western blot, and Annexin V assay. We have shown that monensin suppresses neuroblastoma cell viability, invasion, migration, and colony formation. Moreover, we reported that monensin inhibits cell viability by triggering apoptosis of neuroblastoma cells. Monensin caused apoptosis by increasing caspase-3, 7, 8, and 9 expressions and decreasing Bax and Bcl-2 expressions in neuroblastoma cells. In Annexin V results, the rates of apoptotic cells were found to be 9.66 ± 0.01% (p < 0.001), 29.28 ± 0.88% (p < 0.01), and 62.55 ± 2.36% (p < 0.01) in the 8, 16, and 32 μM monensin groups, respectively. In TUNEL results, these values were, respectively; 35 ± 2% (p < 0.001), 34 ± 0.57% (p < 0.001), and 75 ± 2.51% (p < 0.001). Our results suggest that monensin may be a safe and effective therapeutic candidate for treating pediatric neuroblastoma.
Topics: Humans; Child; Neuroblastoma; Monensin; Annexin A5; Apoptosis; Cell Line, Tumor; Cell Proliferation
PubMed: 37477356
DOI: 10.1111/cts.13593 -
Biomedicine & Pharmacotherapy =... Sep 2022Glioblastoma (GBM) remains the most frequently diagnosed primary malignant brain cancer in adults. Despite recent progress in understanding the biology of GBM, the...
Glioblastoma (GBM) remains the most frequently diagnosed primary malignant brain cancer in adults. Despite recent progress in understanding the biology of GBM, the clinical outcome for patients remains poor, with a median survival of approximately one year after diagnosis. One factor contributing to failure in clinical trials is the fact that traditional models used in GBM drug discovery poorly recapitulate patient tumors. Previous studies have shown that monensin (MON) analogs, namely esters and amides on C-26 were potent towards various types of cancer cell lines. In the present study we have investigated the activity of these molecules in GBM organoids, as well as in a host:tumor organoid model. Using a mini-ring cell viability assay we have identified seven analogs (IC = 91.5 ± 54.4-291.7 ± 68.8 nM) more potent than parent MON (IC = 612.6 ± 184.4 nM). Five of these compounds induced substantial DNA fragmentation in GBM organoids, suggestive of apoptotic cell death. The most active analog, compound 1, significantly reduced GBM cell migration, induced PARP degradation, diminished phosphorylation of STAT3, Akt and GSK3β, increased ɣH2AX signaling and upregulated expression of the autophagy associated marker LC3-II. To investigate the activity of MON and compound 1 in a tumor microenvironment, we developed human cerebral organoids (COs) from human induced pluripotent stem cells (iPSCs). The COs showed features of early developing brain such as multiple neural rosettes with a proliferative zone of neural stem cells (Nestin+), neurons (TUJ1 +), primitive ventricular system (SOX2 +/Ki67 +), intermediate zone (TBR2 +) and cortical plate (MAP2 +). In order to generate host:tumor organoids, we co-cultured RFP-labeled U87MG cells with fully formed COs. Compound 1 and MON reduced U87MG tumor size in the COs after four days of treatment and induced a significant reduction of PARP expression. These findings highlight the therapeutic potential of MON analogs towards GBM and support the application of organoid models in anti-cancer drug discovery.
Topics: Adult; Brain Neoplasms; Cell Line, Tumor; Glioblastoma; Humans; Induced Pluripotent Stem Cells; Monensin; Organoids; Poly(ADP-ribose) Polymerase Inhibitors; Tumor Microenvironment
PubMed: 36076555
DOI: 10.1016/j.biopha.2022.113440 -
Scientific Reports Jan 2023The aim of this study was to conduct a comprehensive review with meta-analysis to determine the effects of the dose-response relationship between monensin... (Meta-Analysis)
Meta-Analysis
The aim of this study was to conduct a comprehensive review with meta-analysis to determine the effects of the dose-response relationship between monensin supplementation and dairy cow performance and milk composition. Results from 566 full-text articles and 48 articles with 52 studies were meta-analyzed for pooled estimates. Monensin supplementation up to 23 ppm increased milk production, with the optimal dose being 12.6 ppm. Monensin supplementation at doses ranging from 16 to 96 ppm increased milk production in the prepartum phase (- 28 to 0 day relative to calving). From 60 to 150 DIM, monensin supplementation up to 21 ppm had a significant positive effect on this outcome, while supplementation in the 37 to 96 ppm range caused a decrease in this variable. At 0 to 60 and > 150 DIM, monensin supplementation had no effect on milk yield. At dosages of 22 to 96 ppm, 12 to 36 ppm, and below 58 ppm and 35 ppm, respectively, monensin supplementation resulted in significant decreases in dry matter intake (DMI), milk protein percentage, milk fat percentage, and milk fat yield. Overall, based on the results of this meta-analysis and considering all variables, the recommended optimal dose of monensin could be about 16 ppm.
Topics: Animals; Cattle; Female; Diet; Dietary Supplements; Lactation; Milk; Milk Proteins; Monensin; Dose-Response Relationship, Drug; Fats
PubMed: 36631508
DOI: 10.1038/s41598-023-27395-9 -
Journal of Animal Science Nov 2017Two experiments evaluated the effect of calcium ammonium nitrate decahydrate (calcium nitrate [NIT]) and monensin sodium (MON) on in vitro fermentation parameters of 2...
Two experiments evaluated the effect of calcium ammonium nitrate decahydrate (calcium nitrate [NIT]) and monensin sodium (MON) on in vitro fermentation parameters of 2 contrasting diets (100:0 and 10:90 forage-to-concentrate ratios). Diet addition of NIT (0, 1.25, and 2.5 g/100 g DM) and MON (0, 3, and 6 mg/L) were tested alone and combined (9 treatments total; 5 bottles per treatment). Mixed ruminal microorganisms were incubated in anaerobic media containing 0.5 g of substrate diet, 1 of 9 treatments, and 40 mL buffer solution. Incubations were performed in batch cultures for 48 h at 39°C. Headspace gas volume was measured and sampled at 4, 8, 12, 24, and 48 h, and the VFA profile was assessed at the end of the experiment. Total gas production was reduced by NIT (87.9 vs. 94.6 mL; < 0.01) and MON (78.6 vs. 94.6 mL; < 0.01) and, in Exp. 2, further reduced by NIT+MON when the additives were combined (161.1 vs. 196.9 mL; < 0.01). Methane production from control in Exp. 1 and Exp. 2 averaged 9.1 and 15.3 mL, respectively, and was decreased by NIT (3.4 and 8.3 mL in Exp. 1 and Exp. 2, respectively; P < 0.01), MON (4.1 and 7.7 mL; in Exp. 1 and Exp. 2, respectively; < 0.01) and NIT+MON (1.1 and 1.5 mL; in Exp. 1 and Exp. 2, respectively; < 0.01). Both experiments demonstrated a significant increase in nitrous oxide (NO; < 0.01) when NIT was added. Compared to the control treatment, IVDMD was reduced when NIT+MON was added at the higher doses in EXP1 (31.7 vs. 37.4%; < 0.01) and EXP2 (76.6 vs. 79.9 %; < 0.01). Net VFA production was not affected by treatments ( > 0.10), but molar proportions of acetate and butyrate were reduced by MON ( < 0.01). Propionate molar proportion was increased in both experiments by MON ( < 0.01) and further increased in Exp. 2 when the additives were combined at lower doses ( < 0.01). Compared to the control treatment, the acetate:propionate (A:P) ratio was reduced by MON in Exp. 1(1.2 vs. 2.8; < 0.01) and Exp. 2 (1.0 vs. 2.3; < 0.01). Fermentation efficiency (%) was increased by MON (81.7 vs. 73.7%; < 0.01) and further increased in Exp. 2 when the additives were combined at lower doses (87.2 vs. 76.6%; < 0.01). The combination of NIT and MON in 2 contrasting diets proved beneficial by altering fermentation products toward lower CH and more propionate; however, the addition of NIT consistently increased NO production. Negative effects of the additives on IVDMD were found only when the additives were combined at higher doses.
Topics: Animal Feed; Animals; Calcium Compounds; Cattle; Diet; Digestion; Female; Fermentation; Methane; Monensin; Nitrates; Rumen
PubMed: 29293719
DOI: 10.2527/jas2017.1657 -
Scientific Reports Nov 2020The investigative material 3-nitrooxypropanol (3-NOP) can reduce enteric methane emissions from beef cattle. North American beef cattle are often supplemented the drug...
The investigative material 3-nitrooxypropanol (3-NOP) can reduce enteric methane emissions from beef cattle. North American beef cattle are often supplemented the drug monensin to improve feed digestibility. Residual and confounding effects of these additives on manure greenhouse gas (GHG) emissions are unknown. This research tested whether manure carbon and nitrogen, and GHG and ammonia emissions, differed from cattle fed a typical finishing diet and 3-NOP [125-200 mg kg dry matter (DM) feed], or both 3-NOP (125-200 mg kg DM) and monensin (33 mg kg DM) together, compared to a control (no supplements) when manure was stockpiled or composted for 202 days. Consistent with other studies, cumulative GHGs (except nitrous oxide) and ammonia emissions were higher from composted compared to stockpiled manure (all P < 0.01). Dry matter, total carbon and total nitrogen mass balance estimates, and cumulative GHG and ammonia emissions, from stored manure were not affected by 3-NOP or monensin. During the current experiment, supplementing beef cattle with 3-NOP did not significantly affect manure GHG or NH emissions during storage under the tested management conditions, suggesting supplementing cattle with 3-NOP does not have residual effects on manure decomposition as estimated using total carbon and nitrogen losses and GHG emissions.
Topics: Air Pollutants; Ammonia; Animal Feed; Animals; Canada; Carbon; Carbon Dioxide; Cattle; Climate; Diet; Greenhouse Gases; Manure; Methane; Monensin; Nitrogen; Nitrous Oxide; Propanols; Rain; Red Meat; Temperature
PubMed: 33168849
DOI: 10.1038/s41598-020-75236-w