-
[Electrophysiological Effects of Ionophore-induced Increases in Intracellular Na in Cardiomyocytes].Yakugaku Zasshi : Journal of the... 2021Na ionophores increase intracellular Na ([Na]i). Membrane potentials and currents were measured using microelectrode and whole-cell patch-clamp techniques. Monensin... (Review)
Review
Na ionophores increase intracellular Na ([Na]i). Membrane potentials and currents were measured using microelectrode and whole-cell patch-clamp techniques. Monensin (10-3×10 M) reduced the slope of the pacemaker potentials and shortened the action potential duration (APD) in sino-atrial nodal and Purkinje cells. Monensin (10 M) shortened the APD and reduced the amplitude of the plateau phase in ventricular myocytes. Monensin decreased the hyperpolarization-activated inward current (I), and it increased the transient outward potassium current (I) in Purkinje cells. In addition, monensin decreased the sodium current (I), shifting the inactivation curve to the hyperpolarized direction. Moreover, monensin decreased the L-type calcium current (I) in ventricular myocytes. The Na-Ca exchange current (I) was augmented particularly in the reverse mode, and the Na-K pump current (I) was also activated by monensin in cardiomyocytes. The ATP-activated potassium current (I) could be induced by monensin. Notably, the inward rectifying K current (I), and the slow delayed outward K current (I) were not affected evidently by monensin. Collectively, alteration of [Na]i can influence the activities of various ion channels and transporters. Thus, the significance of altered [Na]i should be taken into consideration in the action of drugs affecting [Na]i such as digitalis, Na channel blockers, and Na channel activating agents.
Topics: Action Potentials; Animals; Electrophysiological Phenomena; Humans; Monensin; Myocytes, Cardiac; Patch-Clamp Techniques; Potassium; Purkinje Cells; Rabbits; Sinoatrial Node; Sodium; Sodium Ionophores
PubMed: 33952755
DOI: 10.1248/yakushi.20-00235 -
Translational Animal Science 2024This experiment compared narasin and monensin as anticoccidials for calves naturally infected with spp. Twenty-four weaned, non-castrated male calves ( × cross)...
This experiment compared narasin and monensin as anticoccidials for calves naturally infected with spp. Twenty-four weaned, non-castrated male calves ( × cross) were assigned to this experiment (days -8 to 42). All calves were infected by spp. according to oocyst count per gram () from fecal samples collected on days -8 and -7 (average 1,059 ± 101 oocysts/g). Calves were housed in individual pens, received corn silage, mineral mix, and water for ad libitum consumption, in addition to a grain-based supplement at 200 g/head daily. Fecal samples were collected on days -2 and -1 for OPG, and results averaged as initial OPG value. Calves were blocked according to initial OPG into eight blocks of three calves each, ranked within each block according to body weight () recorded on day -1, and assigned to receive narasin ( 0.8 mg/kg of BW), monensin ( 1 mg/kg of BW), or no ionophore (; negative control). Ionophores were added to the grain-based supplement, and offered from days 0 to 42 of the experiment. Calf BW was recorded on days 7, 14, 21, 28, 35, and 42. Fecal samples were collected on days 6 and 7, 13 and 14, 20 and 21, 26 and 27, 34 and 35, and 41 and 42 for OPG analysis, and results from samples collected on consecutive days were averaged. Aliquoted fecal samples were also pooled across calves from the same treatment and collection days, and used to determine the prevalence of individual species of . No treatment effects were detected (≥ 0.51) for calf BW or growth rate. A treatment × day interaction was detected (< 0.01) for OPG, as NAR and MON calves had less (< 0.01) OPG compared with CON calves beginning on day 7. The OPG was also less (≤ 0.03) in MON compared with NAR calves on days 7, 14, and 28, but did not differ (≥ 0.48) on days 21, 35, and 42. The anticoccidial efficacy of NAR and MON did not differ (≥ 0.16) when calculated across all spp., or according to prevalence of and . A treatment × day interaction was detected (= 0.04) for anticoccidial efficacy to , which was greater (< 0.01) in MON calves on days 7 and 14 and did not differ (≥ 0.40) afterward. Collectively, both ionophores were similarly effective in controlling coccidiosis upon completion of the 42-d study, although the anticoccidial effects of monensin were noted earlier in the experiment. Nonetheless, these results corroborate narasin as an efficient anticoccidial ionophore for naturally infected calves.
PubMed: 38800106
DOI: 10.1093/tas/txae069 -
Frontiers in Veterinary Science 2023The objective of this study was to evaluate the effects of different combinations of monensin and narasin on finishing cattle. In Exp. 1, 40 rumen-cannulated Nellore...
The objective of this study was to evaluate the effects of different combinations of monensin and narasin on finishing cattle. In Exp. 1, 40 rumen-cannulated Nellore steers [initial body weight (BW) = 231 ± 3.64 kg] were blocked by initial BW and assigned to one of the five treatments as follows: Control (CON): no feed additive in the basal diet during the entire feeding period; Sodium monensin (MM) at 25 mg/kg dry matter (DM) during the entire feeding period [adaptation (days 1-21) and finishing (days 22-42) periods]; Narasin (NN) at 13 mg/kg DM during the entire feeding period (adaptation and finishing periods); Sodium monensin at 25 mg/kg DM during the adaptation period and narasin at 13 mg/kg DM during the finishing period (MN); and narasin at 13 mg/kg DM during the adaptation period and sodium monensin at 25 mg/kg DM during the finishing period (NM). Steers fed MM had lower dry matter intake (DMI) during the adaptation period compared to NM ( = 0.02) but not compared to CON, MM, MN, or NN ( ≥ 0.12). No differences in DMI were observed among the treatments during the finishing ( = 0.45) or the total feeding period ( = 0.15). Treatments did not affect the nutrient intake ( ≥ 0.51) or the total apparent digestibility of nutrients ( ≥ 0.22). In Exp. 2, 120 Nellore bulls (initial BW = 425 ± 5.4 kg) were used to evaluate the effects of the same treatments of Exp. 1 on growth performance and carcass characteristics of finishing feedlot cattle. Steers fed NM had greater DMI during the adaptation period compared to CON, MM, and MN ( ≤ 0.03), but no differences were observed between NM and NN ( = 0.66) or between CON, MM, and NN ( ≥ 0.11). No other differences between treatments were observed ( ≥ 12). Feeding narasin at 13 mg/kg DM during the adaptation period increases the DMI compared to monensin at 25 mg/kg DM, but the feed additives evaluated herein did not affect the total tract apparent digestibility of nutrients, growth performance, or carcass characteristics of finishing cattle.
PubMed: 37187926
DOI: 10.3389/fvets.2023.1117639 -
BMC Veterinary Research Jul 2022Coccidiosis is a poultry disease that occurs worldwide and is caused by Eimeria species. The infection is associated with reduced feed efficiency, body weight gain,...
BACKGROUND
Coccidiosis is a poultry disease that occurs worldwide and is caused by Eimeria species. The infection is associated with reduced feed efficiency, body weight gain, and egg production. This study aimed to investigate the current status of coccidiosis and anticoccidial resistance to anticoccidial drugs used as part of control strategies for this disease in Korean chicken farms.
RESULTS
An overall prevalence of 75% (291/388) was found. Positive farms contained several Eimeria species (mean = 4.2). Of the positive samples, E. acervulina (98.6%), E. maxima (84.8%), and E. tenella (82.8%) were the most prevalent species. Compared with cage-fed chickens, broilers and native chickens reared in free-range management were more at risk of acquiring an Eimeria infection. Sensitivities to six anticoccidial drugs (clopidol, diclazuril, maduramycin, monensin, salinomycin, and toltrazuril) were tested using nine field samples. Compared with untreated healthy control chickens, the body weight gains of infected chickens and treated/infected chickens were significantly reduced in all groups. Fecal oocyst shedding was significantly reduced in four clopidol-treated/infected groups, three diclazuril-treated/infected groups, two toltrazuril-treated/infected groups, one monensin-treated/infected group, and one salinomycin-treated/infected group, compared with the respective untreated/infected control groups. Intestinal lesion scores were also reduced in three clopidol-treated/infected groups, one monensin-treated/infected group, and one toltrazuril-treated/infected group. However, an overall assessment using the anticoccidial index, percent optimum anticoccidial activity, relative oocyst production, and reduced lesion score index found that all field samples had strong resistance to all tested anticoccidial drugs.
CONCLUSION
The results of this large-scale epidemiological investigation and anticoccidial sensitivity testing showed a high prevalence of coccidiosis and the presence of severe drug resistant Eimeria species in the field. These findings will be useful for optimizing the control of coccidiosis in the poultry industry.
Topics: Animals; Chickens; Clopidol; Coccidiosis; Coccidiostats; Drug Resistance; Eimeria; Farms; Monensin; Oocysts; Poultry Diseases; Republic of Korea; Weight Gain
PubMed: 35836230
DOI: 10.1186/s12917-022-03369-3 -
Animals : An Open Access Journal From... Sep 2022Previous studies have demonstrated that the effects of monensin on methanogenesis and ruminal fermentation in ruminants were time-dependent. To elucidate the underlying...
Previous studies have demonstrated that the effects of monensin on methanogenesis and ruminal fermentation in ruminants were time-dependent. To elucidate the underlying mechanism, we investigated the ruminal bacterial community successions during the adaptation to monensin supplementation and subsequent withdrawal in goats. The experiment included a baseline period of 20 days followed by a treatment period of 55 days with 32 mg monensin/d and a washout period of 15 days. Monensin supplementation reduced the α diversity and changed the structure of ruminal microflora. The α diversity was gradually restored during adaption, but the structure was still reshaped. The temporal dynamics of 261 treatment- and/or time-associated ruminal bacteria displayed six patterns, with two as monensin-sensitive and four as monensin-resistant. The monensin sensitivity and resistance of microbes do not follow a clear dichotomy between Gram-positive and Gram-negative cell types. Moreover, the temporal dynamic patterns of different bacterial species within the same genus or family also displayed variation. Of note, the relative abundance of the total ruminal cellulolytic bacteria gradually increased following monensin treatment, and that of the total amylolytic bacteria were increased by monensin, independent of the duration. In conclusion, under the pressure of monensin, the ruminal ecosystem was reshaped through a series of succession processes, and the carbohydrate-degrading bacteria presented a higher level of adaptability.
PubMed: 36078011
DOI: 10.3390/ani12172291 -
Translational Animal Science Jul 2022The objective of this study was to evaluate the effects of using conventional productivity-enhancing technologies (PETs) with or without other natural PETs on the growth...
The objective of this study was to evaluate the effects of using conventional productivity-enhancing technologies (PETs) with or without other natural PETs on the growth performance, carcass traits, and environmental impacts of feedlot cattle. A total of 768 cross-bred yearling steers (499 ± 28.6 kg; = 384) and heifers (390 ± 34.9 kg; = 384) were offered a barley grain-based basal diet and divided into implanted or non-implanted groups. Steers were then allocated to diets that contained either: (i) no additive (control); natural feed additives including (ii) fibrolytic enzymes (Enz), (iii) essential oil (Oleo), (iv) direct-fed microbial (DFM), (v) DFM + Enz + Oleo combination; conventional feed additives including (vi) Conv (monensin, tylosin, and beta-adrenergic agonists [βAA]); or Conv with natural feed additives including (vii) Conv + DFM + Enz; (viii) Conv + DFM + Enz + Oleo. Heifers received one of the first three dietary treatments or the following: (iv) probiotic (Citr); (v) Oleo + Citr; (vi) Melengesterol acetate (MGA) + Oleo + βAA; (vii) Conv (monensin, tylosin, βAA, and MGA); or (viii) Conv + Oleo (ConvOleo). Data were used to estimate greenhouse gas (GHG) and ammonia (NH) emissions, as well as land and water use. Implant and Conv-treated cattle exhibited improvements in growth and carcass traits as compared to the other treatments ( < 0.05). Improvements in the performance of Conv-cattle illustrated that replacing conventional feed additives with natural feed additives would increase both the land and water required to satisfy the feed demand of steers and heifers by 7.9% and 10.5%, respectively. Further, GHG emission intensity for steers and heifers increased by 5.8% and 6.7%, and NH emission intensity by 4.3% and 6.7%, respectively. Eliminating the use of implants in cattle increased both land and water use by 14.6% and 19.5%, GHG emission intensity by 10.5% and 15.8%, and NH emission intensity by 3.4% and 11.0% for heifers and steers, respectively. These results demonstrate that the use of conventional PETs increases animal performance while reducing the environmental impacts of beef production. Restricting use would increase the environmental footprint of beef produced for both domestic and international markets.
PubMed: 37283958
DOI: 10.1093/tas/txac074 -
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 -
International Journal For Parasitology.... Aug 2023Worldwide distributed coccidiosis is caused by infection of both Eimeria species and Cystoisospora in the host intestine and causes huge economic losses to the livestock...
Worldwide distributed coccidiosis is caused by infection of both Eimeria species and Cystoisospora in the host intestine and causes huge economic losses to the livestock industry, especially the poultry industry. The control of such diseases relies mainly on chemoprophylaxis with anticoccidials, which has led to a very common drug resistance in this field. However, the genetic mechanisms underlying resistance to many anticoccidial drugs remain unknown. In this study, strains of E. tenella resistant to 250 mg/kg monensin were generated and characterized. Forward genetic approaches based on pooled genome sequencing, including experimental evolution and linkage group selection, were used to locate candidate targets responsible for resistance to monensin and diclazuril in E. tenella. A total of 16 nonsynonymous mutants in protein-coding genes were identified in monensin-resistant strains, and two genomic regions with strong selection signals were also detected in diclazuril-resistant strains. Our study reveals the genetic characterization of the experimental evolution and linkage group selection in Eimeria species, and also provides important information that contributes to the understanding of the molecular mechanism of drug resistance in coccidia.
Topics: Animals; Monensin; Eimeria tenella; Coccidiostats; Chickens; Poultry Diseases; Coccidiosis; Eimeria
PubMed: 37247559
DOI: 10.1016/j.ijpddr.2023.05.002 -
Veterinary Medicine and Science Sep 2023Grazing in arid and semi-arid regions faces pregnant ewes with feed restrictions and hence affects the offspring muscle fibre characteristics. Using feed additives that...
Restricted maternal nutrition and supplementation of propylene glycol, monensin sodium and rumen-protected choline chloride during late pregnancy does not affect muscle fibre characteristics of offspring.
BACKGROUND
Grazing in arid and semi-arid regions faces pregnant ewes with feed restrictions and hence affects the offspring muscle fibre characteristics. Using feed additives that enhance nutrient availability during foetal muscle development is expected to alter offspring skeletal muscle characteristics.
OBJECTIVES
This study evaluated the effect of maternal restricted nutrition and supplementation of propylene glycol, monensin sodium and rumen-protected choline chloride on lamb's muscle fibre characteristics.
METHODS
Forty-eight Ghezel ewes were randomly allocated to one of six diets (N = 8) during the last 6 weeks of gestation: ad libitum feed intake (AL); restricted feeding (RF); restricted feeding containing propylene glycol (PG); restricted feeding containing propylene glycol and monensin sodium (MS); restricted feeding containing propylene glycol and rumen-protected choline chloride (RPC); restricted feeding containing propylene glycol, monensin sodium and rumen-protected choline chloride (PMC). The muscle samples were obtained from the semitendinosus muscle of 2-week-old male lambs (n = 5/treatment) via biopsy and were stained and classified as fibre types I, IIA and IIB.
RESULTS
Pre-parturient maternal feed restriction and administration of propylene glycol, monensin sodium and rumen-protected choline chloride had no significant effect on fibre-type composition, fibre density of muscle, muscle cross-sectional area and volume density of fibres (p > 0.05).
CONCLUSIONS
Either maternal dietary restriction or supplementation of nutrient flux-involved additives during late pregnancy did not alter muscle fibre development and had no short-term effects on muscle properties of the resulting offspring as myogenesis occurs in early and mid-gestation, not late gestation. Therefore, maternal nutrition may not be a problematic issue in sheep production in arid and semi-arid areas.
Topics: Pregnancy; Animals; Sheep; Female; Male; Monensin; Choline; Rumen; Propylene Glycol; Muscle Fibers, Skeletal; Dietary Supplements
PubMed: 37556348
DOI: 10.1002/vms3.1239 -
International Journal of Molecular... Mar 2021We performed a comparative analysis of two ER-resident CREB3 family proteins, CREB3 and CREB3L2, in HEK293 cells using pharmacological and genome editing approaches and... (Comparative Study)
Comparative Study
We performed a comparative analysis of two ER-resident CREB3 family proteins, CREB3 and CREB3L2, in HEK293 cells using pharmacological and genome editing approaches and identified several differences between the two. Treatment with brefeldin A (BFA) and monensin induced the cleavage of full-length CREB3 and CREB3L2; however, the level of the full-length CREB3 protein, but not CREB3L2 protein, was not noticeably reduced by the monensin treatment. On the other hand, treatment with tunicamycin (Tm) shifted the molecular weight of the full-length CREB3L2 protein downward but abolished CREB3 protein expression. Thapsigargin (Tg) significantly increased the expression of only full-length CREB3L2 protein concomitant with a slight increase in the level of its cleaved form. Treatment with cycloheximide and MG132 revealed that both endogenous CREB3 and CREB3L2 are proteasome substrates. In addition, kifunensine, an α-mannosidase inhibitor, significantly increased the levels of both full-length forms. Consistent with these findings, cells lacking SEL1L, a crucial ER-associated protein degradation (ERAD) component, showed increased expression of both full-length CREB3 and CREB3L2; however, cycloheximide treatment downregulated full-length CREB3L2 protein expression more rapidly in SEL1L-deficient cells than the full-length CREB3 protein. Finally, we investigated the induction of the expression of several CREB3 and CREB3L2 target genes by Tg and BFA treatments and SEL1L deficiency. In conclusion, this study suggests that both endogenous full-length CREB3 and CREB3L2 are substrates for ER-associated protein degradation but are partially regulated by distinct mechanisms, each of which contributes to unique cellular responses that are distinct from canonical ER signals.
Topics: Alkaloids; Basic-Leucine Zipper Transcription Factors; Cyclic AMP Response Element-Binding Protein; Cycloheximide; Gene Expression Regulation; HEK293 Cells; Humans; Leupeptins; Proteins
PubMed: 33803345
DOI: 10.3390/ijms22052767