-
Anais Da Academia Brasileira de Ciencias 2022This study assessed the association between encapsulated nitrate product (ENP) and monensin (MON) to mitigate enteric methane (CH4) in vitro and possible effects on...
This study assessed the association between encapsulated nitrate product (ENP) and monensin (MON) to mitigate enteric methane (CH4) in vitro and possible effects on ruminal degradability, enteric fermentation characteristics, and microbial populations. Six treatments were used in randomized complete design in a 2×3 factorial arrangement with two levels of MON (0 and 2.08 mg/mL of buffered rumen fluid) and three levels of ENP (0, 1.5 and 3.0%). The substrate consisted of 50% Tifton-85 hay and 50% concentrate mixture (ground corn and soybean meal). ENP replaced soybean meal to achieve isonitrogenous diets (15% CP). No ENP×MON interaction was observed for any measured variable (P > 0.05) except for the relative abundance of F. succinogenes (P = 0.02) that linearly increased in diets with MON when ENP was added. The ENP addition decreased CH4 production (P < 0.01) without affecting (P > 0.05) truly degraded organic matter nor the relative abundance of methanogens. Hydrogen production was reduced with MON (P = 0.04) and linearly decreased with ENP inclusion (P = 0.02). We concluded that use of nitrate is a viable strategy for CH4 reduction, however, no additive effect of ENP and MON was observed for mitigating CH4 production.
Topics: Animals; Diet; Fermentation; Monensin; Nitrates; Rumen; Glycine max
PubMed: 36102387
DOI: 10.1590/0001-3765202220200213 -
Poultry Science Feb 1987We studied the effect of sulfadiomethoxine and ormetoprim (Rofenaid 40) in combination with lasalocid (Avatec) and monensin (Coban) on mortality, weight gain, and feed... (Comparative Study)
Comparative Study
We studied the effect of sulfadiomethoxine and ormetoprim (Rofenaid 40) in combination with lasalocid (Avatec) and monensin (Coban) on mortality, weight gain, and feed conversion of 2592 male broilers to 47 days of age. Four shuttle treatments were utilized: 1) monensin feeding for the entire trial; 2) sulfadimethoxine and ormetoprim feeding for the first 2 weeks, followed by lasalocid for the remainder of the trial; 3) sulfadimethoxine and ormetoprim feeding for the first 2 weeks, followed by monensin; and 4) sulfadimethoxine and ormetoprim feeding through week 3, then lasalocid for the remainder of the trial. No significant (P greater than .05) differences were observed in mortality among the four treatments. The combination of sulfadimethoxine and ormetoprim plus lasalocid significantly (P less than .01) improved weight gain and final body weight, but the length of time that sulfadimethoxine and ormetoprim were fed did not have any effect. Sulfadimethoxine and ormetoprim plus monensin treatment resulted in better feed conversion as compared with the other treatments.
Topics: Animals; Body Weight; Chickens; Lasalocid; Male; Monensin; Pyrimidines; Sulfadimethoxine
PubMed: 3588507
DOI: 10.3382/ps.0660373 -
Biomolecules Jul 2020Polyether ionophores represent a group of natural lipid-soluble biomolecules with a broad spectrum of bioactivity, ranging from antibacterial to anticancer activity....
Polyether ionophores represent a group of natural lipid-soluble biomolecules with a broad spectrum of bioactivity, ranging from antibacterial to anticancer activity. Three seem to be particularly interesting in this context, namely lasalocid acid, monensin, and salinomycin, as they are able to selectively target cancer cells of various origin including cancer stem cells. Due to their potent biological activity and abundant availability, some research groups around the world have successfully followed semi-synthetic approaches to generate original derivatives of ionophores. However, a definitely less explored avenue is the synthesis and functional evaluation of their multivalent structures. Thus, in this paper, we describe the synthetic access to a series of original homo- and heterodimers of polyether ionophores, in which (i) two salinomycin molecules are joined through triazole linkers, or (ii) salinomycin is combined with lasalocid acid, monensin, or betulinic acid partners to form 'mixed' dimeric structures. Of note, all 11 products were tested in vitro for their antiproliferative activity against a panel of six cancer cell lines including the doxorubicin resistant colon adenocarcinoma LoVo/DX cell line; five dimers (-, - and ) were identified to be more potent than the reference agents (i.e., both parent compound(s) and commonly used cytostatic drugs) in selective targeting of various types of cancer. Dimers and were also found to effectively overcome the resistance of the LoVo/DX cancer cell line.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cell Survival; Ethers; Humans; Ionophores; Lasalocid; Molecular Structure; Monensin; Pentacyclic Triterpenes; Polymerization; Pyrans; Betulinic Acid
PubMed: 32664671
DOI: 10.3390/biom10071039 -
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 -
Toxins Feb 2023-glycolylneuraminic acid (Neu5Gc) is a specific factor in red meat that induces intestinal disease. Our aim was to investigate the effect of Neu5Gc on the intestinal...
-glycolylneuraminic acid (Neu5Gc) is a specific factor in red meat that induces intestinal disease. Our aim was to investigate the effect of Neu5Gc on the intestinal barrier as well as its mechanism of endocytosis and exocytosis. Ten specific inhibitors were used to explore the mechanism of Neu5Gc endocytosis and exocytosis by Caco-2 cells. Amiloride hydrochloride and cytochalasin D had the strongest inhibitory effect on the endocytosis of Neu5Gc. Sodium azide, dynasore, chlorpromazine hydrochloride, and nystatin also inhibited Neu5Gc endocytosis. Dynasore exhibited a stronger inhibitory effect than that of chlorpromazine hydrochloride or nystatin alone. Exocytosis inhibitors, including nocodazole, brefeldin A, monensin, and bafilomycin A, inhibited the transmembrane transport of Neu5Gc. Monensin promoted the exocytosis of Neu5Gc from Caco-2 cells. In another experiment, we observed no significant inhibitory effects of monensin and brefeldin A. Dietary concentrations of Neu5Gc induced prominent damage to intestinal tight junction proteins zonula occludens-1 (ZO-1), occludin, and claudin-1 and promoted the phosphorylation of IκB-α and P65 to activate the canonical Nuclear Factor kappa-B (NF-κB) pathway. Neu5Gc increased the RNA levels of pro-inflammatory factors IL-1β, IL-6, and TNF-α and inhibited those of anti-inflammatory factors TGF-β and IL-10. BAY, an NF-κB signaling pathway inhibitor, attenuated these changes. Reductions in the levels of ZO-1, occludin, and claudin-1 were recovered in response to BAY. Our data reveal the endocytosis and exocytosis mechanism of Neu5Gc and prove that Neu5Gc can activate the canonical NF-κB signaling pathway, regulate the transcription of inflammatory factors, thereby damaging intestinal barrier function.
Topics: Humans; NF-kappa B; Caco-2 Cells; Occludin; Claudin-1; Brefeldin A; Chlorpromazine; Monensin; Nystatin; Signal Transduction; Intestinal Mucosa
PubMed: 36828446
DOI: 10.3390/toxins15020132 -
Journal of Animal Science Jun 2018The study objective was to evaluate the combined effects of supplementing monensin (MON) and the methane (CH4) inhibitor 3-nitrooxypropanol (NOP) on enteric CH4...
The combined effects of supplementing monensin and 3-nitrooxypropanol on methane emissions, growth rate, and feed conversion efficiency in beef cattle fed high-forage and high-grain diets.
The study objective was to evaluate the combined effects of supplementing monensin (MON) and the methane (CH4) inhibitor 3-nitrooxypropanol (NOP) on enteric CH4 emissions, growth rate, and feed conversion efficiency of backgrounding and finishing beef cattle. Two hundred and forty crossbred steers were used in a 238-d feeding study and fed a backgrounding diet for the first 105 d (backgrounding phase), transition diets for 28 d, followed by a finishing diet for 105 d (finishing phase). Treatments were as follows: 1) control (no additive); 2) MON (monensin supplemented at 33 mg/kg DM; 3) NOP (3-nitrooxypropanol supplemented at 200 mg/kg DM for backgrounding or 125 mg/kg DM for finishing phase); and 4) MONOP (33 mg/kg DM MON supplemented with either 200 mg/kg DM or 125 mg/kg DM NOP). The experiment was a randomized complete block (weight: heavy and light) design with 2 (NOP) × 2 (MON) factorial arrangement of treatments using 24 pens (8 cattle/pen; 6 pens/treatment) at the main feedlot and 8 pens (6 cattle/pen; 2 pens/treatment) at the controlled environment building (CEB) feedlot. Five animals per treatment were moved to chambers for CH4 measurements during both phases. Data were analyzed using a Mixed procedure of SAS with pen as experimental unit (except CH4). Location (Main vs. CEB) had no significant effect and was thus omitted from the final model. Overall, there were few interactions between MON and NOP indicating that the effects of the 2 compounds were independent. When cattle were fed the backgrounding diet, pen DMI was decreased by 7%, whereas gain-to-feed ratio (G:F) was improved by 5% with NOP supplementation (P < 0.01). Similarly, MON improved G:F ratio by 4% (P < 0.01), but without affecting DMI. During the finishing phase, DMI tended (P = 0.06) to decrease by 5% with both MON (5%) and NOP (5%), whereas ADG tended (P = 0.08) to decrease by 3% with MON. Gain-to-feed ratio for finishing cattle was improved with NOP by 3% (P < 0.01); however, no effects were observed with MON. 3-Nitrooxypropanol decreased CH4 yield (g/kg DMI) by 42% and 37% with backgrounding and finishing diets (P ≤ 0.01), respectively, whereas MON did not lower CH4 yield. Overall, these results demonstrate efficacy of NOP in reducing enteric CH4 emissions and subsequently improving feed conversion efficiency in cattle fed high-forage and high-grain diets. Furthermore, effects of NOP did not depend on whether MON was included in the diet.
Topics: Animal Feed; Animals; Cattle; Diet; Dietary Supplements; Edible Grain; Male; Methane; Monensin; Propanols
PubMed: 29741701
DOI: 10.1093/jas/sky174 -
Journal of Dairy Science Apr 2017Evidence exists that dairy cows experience inflammatory-like phenomena in the transition period. Rumen health and alterations in metabolic processes and gene networks in...
Effects of body condition, monensin, and essential oils on ruminal lipopolysaccharide concentration, inflammatory markers, and endoplasmatic reticulum stress of transition dairy cows.
Evidence exists that dairy cows experience inflammatory-like phenomena in the transition period. Rumen health and alterations in metabolic processes and gene networks in the liver as the central metabolic organ might be key factors for cows' health and productivity in early lactation. This study made use of an animal model to generate experimental groups with different manifestations of postpartal fat mobilization and ketogenesis. In total, 60 German Holstein cows were allocated 6 wk antepartum to 3 high-body condition score (BCS) groups (BCS 3.95) and 1 low-BCS group (LC; BCS 2.77). High-BCS cows were fed an antepartal forage-to-concentrate ratio of 40:60 on dry matter basis, in contrast to 80:20 in the LC group, and received a monensin controlled-release capsule (HC/MO), a blend of essential oils (HC/EO), or formed a control group (HC). We evaluated serum haptoglobin, kynurenine, tryptophan, ruminal lipopolysaccharide concentration and mRNA abundance of nuclear factor kappa B (NF-κB), nuclear factor E2-related factor 2 (Nrf2), and endoplasmatic reticulum stress-induced unfolded protein response (UPR) target genes in liver biopsy samples from d -42 until +56 relative to calving. Nearly all parameters were highly dependent on time, with greatest variation near calving. The ruminal lipopolysaccharide concentration and evaluated target genes were not generally influenced by antepartal BCS and feeding management. The kynurenine-to-tryptophan ratio was higher in LC than in HC/MO treatment on d 7. Ruminal lipopolysaccharide concentration was higher in HC/MO than in the HC group, but not increased in HC/EO group. Abundance of UPR target gene X-box binding protein 1 was higher in HC/MO than in HC/EO group on d 7. Hepatic mRNA abundance of Nrf2 target gene glutathione peroxidase 3 was higher, whereas expression of NF-κB target gene haptoglobin tended to be higher in LC than in HC/EO cows. The HC/MO cows showed the most prominent increase in the abundance of glutathione peroxidase 3 and haptoglobin after calving in comparison to antepartal values. Results indicate the presence of inflammatory-like phenomena near calving. Simultaneously, alterations in UPR and Nrf2 target genes with antioxidative properties and haptoglobin occurred, being most prominent in LC and HC/MO group.
Topics: Animals; Cattle; Diet; Female; Lactation; Milk; Monensin; Oils, Volatile; Reticulum; Rumen
PubMed: 28215897
DOI: 10.3168/jds.2016-11819 -
Applied and Environmental Microbiology Jan 1989
Review
Topics: Animals; Bacteria; Biological Transport, Active; Cell Membrane; Drug Resistance, Microbial; Fermentation; Ionophores; Lasalocid; Methane; Monensin; Rumen
PubMed: 2650616
DOI: 10.1128/aem.55.1.1-6.1989 -
Cellular Physiology and Biochemistry :... 2010Eryptosis, the suicidal erythrocyte death, is characterized by cell membrane scrambling and cell shrinkage. Eryptosis may be triggered by excessive hyperosmotic or...
Eryptosis, the suicidal erythrocyte death, is characterized by cell membrane scrambling and cell shrinkage. Eryptosis may be triggered by excessive hyperosmotic or isosmotic cell shrinkage leading to increase of cytosolic Ca(2+) concentration. Eryptosis is further stimulated by the K(+) ionophore valinomycin, which leads to exit of KCl and osmotically obliged water, or by energy (glucose) depletion, which compromises the function of the Na(+)/K(+) ATPase thus increasing cytosolic Na(+) concentration. The present study explored whether the Na(+) ionophore monensin affects erythrocyte cell volume and eryptosis. The cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, cell volume from forward scatter in FACS analysis, cytosolic Ca(2+) concentration from Fluo3 fluorescence and the cytosolic ATP concentration from a luciferase-based assay. Within 24 hours, exposure to monensin (0.1-10 microg/ml) significantly increased forward scatter, cytosolic Ca(2+) concentration and annexin V-binding. Glucose depletion was followed by decreased forward scatter and increased cytosolic Ca(2+) concentration and annexin V-binding. The effect on forward scatter was partially reversed, the effect on cytosolic Ca(2+) concentration and annexin V binding augmented by additional treatment with monensin. In conclusion, monensin dissociates the alterations of cell membrane and cell volume in suicidal erythrocyte death.
Topics: Cell Death; Cell Membrane; Cell Size; Erythrocytes; Humans; Ionophores; Monensin
PubMed: 20511720
DOI: 10.1159/000315094 -
Nature Chemistry Jan 2021Polyether ionophores are complex natural products capable of transporting cations across biological membranes. Many polyether ionophores possess potent antimicrobial...
Polyether ionophores are complex natural products capable of transporting cations across biological membranes. Many polyether ionophores possess potent antimicrobial activity and a few selected compounds have the ability to target aggressive cancer cells. Nevertheless, ionophore function is believed to be associated with idiosyncratic cellular toxicity and, consequently, human clinical development has not been pursued. Here, we demonstrate that structurally novel polyether ionophores can be efficiently constructed by recycling components of highly abundant polyethers to afford analogues with enhanced antibacterial selectivity compared to a panel of natural polyether ionophores. We used classic degradation reactions of the natural polyethers lasalocid and monensin and combined the resulting fragments with building blocks provided by total synthesis, including halogen-functionalized tetronic acids as cation-binding groups. Our results suggest that structural optimization of polyether ionophores is possible and that this area represents a potential opportunity for future methodological innovation.
Topics: Aldehydes; Anti-Bacterial Agents; Cell Line; Cell Survival; Crystallography, X-Ray; Ethers; Furans; Humans; Ionophores; Lasalocid; Molecular Conformation; Monensin; Oxidation-Reduction
PubMed: 33353970
DOI: 10.1038/s41557-020-00601-1