Investigation of the anticancer mechanism of monensin via apoptosis-related factors in SH-SY5Y neuroblastoma cells.

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.

Forward genetic analysis of monensin and diclazuril resistance in Eimeria tenella.

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.

Boosting intracellular sodium selectively kills hepatocarcinoma cells and induces hepatocellular carcinoma tumor shrinkage in mice.

Pharmacological treatments for advanced hepatocellular carcinoma (HCC) have a partial efficacy. Augmented Na+ content and water retention are observed in human cancers and offer unexplored targets for anticancer therapies. Na+ levels are evaluated upon treatments with the antibiotic cation ionophore Monensin by fluorimetry, ICP-MS, 23Na-MRI, NMR relaxometry, confocal or time-lapse analysis related to energy production, water fluxes and cell death, employing both murine and human HCC cell lines, primary murine hepatocytes, or HCC allografts in NSG mice. Na+ levels of HCC cells and tissue are 8-10 times higher than that of healthy hepatocytes and livers. Monensin further increases Na+ levels in HCC cells and in HCC allografts but not in primary hepatocytes and in normal hepatic and extrahepatic tissue. The Na+ increase is associated with energy depletion, mitochondrial Na+ load and inhibition of O2 consumption. The Na+ increase causes an enhancement of the intracellular water lifetime and death of HCC cells, and a regression and necrosis of allograft tumors, without affecting the proliferating activity of either HCCs or healthy tissues. These observations indicate that HCC cells are, unlike healthy cells, energetically incapable of compensating and surviving a pharmacologically induced Na+ load, highlighting Na+ homeostasis as druggable target for HCC therapy.

Monensin synergizes with chemotherapy in uveal melanoma through suppressing RhoA.

OBJECTIVE: Uveal melanoma (UM) is the common primary cancer of the eye and new treatments are needed. Substantial evidence has shown that an antibiotic monensin is an attractive candidate for the development of anti-cancer drug. In this study, we investigated the potential of repositioning monensin for the treatment of UM in the pre-clinical setting. MATERIALS AND METHODS: Cellular activity assays were performed using multiple cell lines representing UM models with different cellular origins and genetic profiling and normal cells as control. Combination studies were performed using Chou-Talalay method. Mechanism studies were performed using immunoblotting and ELISA. RESULTS: Monensin was effective against all tested UM cell lines and less effective against normal fibroblast cells. Monensin induced G0/G1 arrest and thus decreased S phase, leading to UM cell growth inhibition. It also inhibited migration and induced apoptosis in UM cells. In addition, the combination of monensin and dacarbazine was synergistic in targeting UM cells. Our mechanistic studies showed that monensin specifically decreased activity of RhoA without affecting other small GTPases, such as Ras and Rac1. Consistently, monensin decreased phosphorylation of downstream effectors of RhoA signaling, including ROCK, MYPT1 and MLC. Rescue studies using RhoA activator calpeptin showed that calpeptin significantly abolished the inhibitory effects of monensin on RhoA activity, proliferation, migration and survival, confirming that RhoA is the target of monensin in UM cells. CONCLUSIONS: Our study demonstrates that monensin is a potent inhibitor of UM and synergizes with chemotherapy, via suppressing RhoA activity and RhoA-mediated signaling. Our findings suggest that monensin may be a potential lead compound for further development into a drug for UM treatment.

Anti-glioblastoma activity of monensin and its analogs in an organoid model of cancer.

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 (IC50 = 91.5 ± 54.4-291.7 ± 68.8 nM) more potent than parent MON (IC50 = 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 GSK3ß, increased É£H2AX 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.

Monensin Inhibits Anaplastic Thyroid Cancer via Disrupting Mitochondrial Respiration and AMPK/mTOR Signaling.

OBJECTIVE: The clinical management of anaplastic thyroid cancer (ATC) remains challenging, and novel treatment methods are needed. Monensin is a carboxyl polyether ionophore that potently inhibits the growth of various cancer types. Our current work investigates whether monensin has selective anti-ATC activity and systematically explores its underlying mechanisms. METHODS: Proliferation and apoptosis assays were performed using a panel of thyroid cancer cell lines. Mitochondrial biogenesis profiles, ATP levels, oxidative stress, AMPK, and mTOR were examined in these cells after monensin treatment. RESULTS: Monensin is effective in inhibiting proliferation and inducing apoptosis in a number of thyroid cancer cell lines. The results are consistent across cell lines of varying cellular origins and genetic mutations. Compared to other thyroid cancer cell types, ATC cell lines are the most sensitive to monensin. Of note, monensin used at our experimental concentration affects less of normal cells. Mechanistic studies reveal that monensin acts on ATC cells by disrupting mitochondrial function, inducing oxidative stress and damage, and AMPK activation-induced mTOR inhibition. We further show that mitochondrial respiration is a critical target for monensin in ATC cells. CONCLUSIONS: Our pre-clinical findings demonstrate the selective anti-ATC activities of monensin. This is supported by increasing evidence that monensin can be repurposed as a potential anti-cancer drug.

Monensin inhibits glioblastoma angiogenesis via targeting multiple growth factor receptor signaling.

Glioblastoma is characterized by the extensive vascularization with poor prognosis. Targeting both tumor cell and angiogenesis may present an effective therapeutic strategy for glioblastoma. Monensin, a polyether ionophore antibiotic, has been recently recognized as promising anticancer drug candidate due to its potent and selective anti-tumor activities. However, little is known on the effects of monensin on tumor angiogenesis. In this work, we investigated the effects and underlying mechanisms of monensin on glioblastoma angiogenesis and growth. We show that monensin at nanomolar concentrations inhibits early stages of capillary network formation of glioblastoma endothelial cell. Monensin inhibited multiple endothelial cellular events, including migration, growth and survival, without affecting adhesion to Matrigel. We further demonstrate that monensin acts on endothelial cells via suppressing VEGFR- and EGFR-mediated signaling pathways. Monensin also inhibits proliferation and induces apoptosis in a panel of glioblastoma cells. However, monensin is more effective in targeting endothelial cells than tumor cells. Using glioblastoma growth xenograft mice model, we show that monensin at tolerable dose effectively inhibits glioblastoma growth. Of note, there is a significant decreased tumor vascularization from monensin-treated mice. Our work clearly demonstrates the anti-angiogenic activity of monensin and its ability in suppressing multiple tyrosine kinase receptor-mediated pathways. Our findings suggest that is a useful addition to the treatment armamentarium for glioblastoma.

Golgi organization is regulated by proteasomal degradation.

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.

Doxycycline, salinomycin, monensin and ivermectin repositioned as cancer drugs.

Chemotherapy is one of the standard methods for the treatment of malignant tumors. It aims to cause lethal damage to cellular structures, mainly DNA. Noteworthy, in recent years discoveries of novel anticancer agents from well-known antibiotics have opened up new treatment pathways for several cancer diseases. The aim of this review article is to describe new applications for the following antibiotics: doxycycline (DOX), salinomycin (SAL), monensin (MON) and ivermectin (IVR) as they are known to show anti-tumor activity, but have not yet been introduced into standard oncological therapy. To date, these agents have been used for the treatment of a broad-spectrum of bacterial and parasitic infectious diseases and are widely available, which is why they were selected. The data presented here clearly show that the antibiotics mentioned above should be recognised in the near future as novel agents able to eradicate cancer cells and cancer stem cells (CSCs) across several cancer types.

Salinomycin derivatives exhibit activity against primary acute lymphoblastic leukemia (ALL) cells in vitro.

Salinomycin (SAL) and monensin (MON) are polyether ionophore antibiotics commonly used in veterinary medicine. They are known from their anti-cancer activity against various types of cancer cells, including those that display multi-drug resistance as well as cancer stem cells. In order to increase the biological activity profile and reduce toxicity against normal cells, while retaining the activities in the micromolar range, a library of ester and amide derivatives of SAL was synthesized and previously reported. In this paper, we examined the activity of SAL, its ten derivatives, and MON on primary acute lymphoblastic leukemia cells. MON and six SAL derivatives were more potent than SAL in cell viability assays. Further, selected active SAL analogs induced characteristics of apoptotic cell death and increased expression of p53. Moreover, SAL acted synergistically with the Bcl-2 inhibitor ABT-263, whereas 2,2,2-trifluoroethyl ester, the most active analog of SAL, antagonized ABT-263, suggesting possible differences in molecular mechanism.

Monensin inhibits canonical Wnt signaling in human colorectal cancer cells and suppresses tumor growth in multiple intestinal neoplasia mice.

The Wnt signaling pathway is required during embryonic development and for the maintenance of homeostasis in adult tissues. However, aberrant activation of the pathway is implicated in a number of human disorders, including cancer of the gastrointestinal tract, breast, liver, melanoma, and hematologic malignancies. In this study, we identified monensin, a polyether ionophore antibiotic, as a potent inhibitor of Wnt signaling. The inhibitory effect of monensin on the Wnt/ß-catenin signaling cascade was observed in mammalian cells stimulated with Wnt ligands, glycogen synthase kinase-3 inhibitors, and in cells transfected with ß-catenin expression constructs. Furthermore, monensin suppressed the Wnt-dependent tail fin regeneration in zebrafish and Wnt- or ß-catenin-induced formation of secondary body axis in Xenopus embryos. In Wnt3a-activated HEK293 cells, monensin blocked the phoshorylation of Wnt coreceptor low-density lipoprotein receptor related protein 6 and promoted its degradation. In human colorectal carcinoma cells displaying deregulated Wnt signaling, monensin reduced the intracellular levels of ß-catenin. The reduction attenuated the expression of Wnt signaling target genes such as cyclin D1 and SP5 and decreased the cell proliferation rate. In multiple intestinal neoplasia (Min) mice, daily administration of monensin suppressed progression of the intestinal tumors without any sign of toxicity on normal mucosa. Our data suggest monensin as a prospective anticancer drug for therapy of neoplasia with deregulated Wnt signaling.

Effect of the granulometric characteristics of monensin sodium on controlling experimental coccidiosis in broiler chickens / Efeito das características granulométricas da monensina sódica no controle da coccidiose experimental em frangos de corte

The aim of the present study was to investigate the efficacy of monensin sodium grain size on controlling coccidiosis in broiler chickens. Three hundred and fifty Cobb 700 chicks were infected experimentally with 8 × 10(4) sporulated oocysts of Eimeria spp. The birds were fed with diets supplemented with powdered (n = 150) or granulated (n = 150) monensin, with particle sizes of ≤100 µm and 450-650 µm, respectively. The remaining chicks (n = 50) were used as an unmedicated control group. The birds’ weights and number of oocysts per gram of litter in each group were recorded weekly. A total of 96 birds were randomly selected and culled during the trial. Their intestinal oocyst counts and lesion scores were determined. No significant differences in body weights were found between the groups at the end of the study. The percentages of infected animals, oocyst counts and lesion scores were significantly higher in the control group than in the other two groups; the two treated groups did not show any appreciable differences to each other. Enteritis was observed in 14 birds, all in the group supplemented with granulated monensin. These results suggest that powdered and granulated monensin have comparable efficacy in controlling coccidiosis in broiler chickens. However, treatments with monensin sodium of high grain size may be subject to contraindications relating to enteritis.

O presente estudo teve como objetivo investigar a eficácia da monensina sódica com diferentes granulometrias no controle da coccidiose em frangos de corte. Trezentos e cinquenta pintos Cobb 700 foram infectados experimentalmente, utilizando-se 8 × 10(4) oocistos esporulados de Eimeria spp. As aves foram alimentadas com dietas suplementadas com monensina em pó (n = 150) ou granulada (n = 150), com partículas de dimensão ≤100 µm e de 450-650 µm respetivamente. As aves restantes (n = 50) foram utilizadas como grupo controle não sujeito a tratamento. O peso das aves e o número de oocistos por grama de material de cama de cada grupo foram avaliados semanalmente. Um total de 96 aves foi selecionado aleatoriamente e submetidos à eutanásia durante o período experimental. Nestas aves foram analisados o número de oocistos intestinais e o respectivo escore das lesões. Não foram encontradas diferenças significativas relativas ao peso dos animais dos diferentes grupos no final do período experimental. A proporção de animais infectados, a quantidade de oocistos e o escore das lesões foram significativamente superiores no grupo de controle, quando comparado com os dois grupos tratados, não encontrando diferenças significativas entre estes últimos. Foi observada enterite em 14 aves, pertencentes ao grupo suplementado com monensina granulada. Estes resultados indicam que a eficácia da monensina em pó e granulada é semelhante no controle de coccidiose em frangos de corte. No entanto, o tratamento com monensina sódica de elevada granulometria pode ser objeto de contraindicações associadas à enterite.

Hematological changes in case of chronic cadmium intoxication and monensin detoxication. Relationship with rheological variables.

The study evaluated the affect of chronic cadmium (Cd) and monensin treatment on some hematological parameters and its relationship with the rheological variables. Adult male mice were subjected to chronic treatment with cadmium acetate [Cd(CH3COO)2 × 2H2O] (group 1), Cd(CH3COO)2 × 2H2O followed by treatment with low dose monensin (group 2) and Cd(CH3COO)2 × 2H2O followed by high dose monensin treatment (group 3). Cd(CH3COO)2 × 2H2O and deprotonated monensin were dissolved in distilled water and given daily to the experimental animals. Mice drinking distilled water served as a control group (group 4). Hematological parameters and erythrocyte morphology were evaluated in parallel with whole blood viscosity (WBV). Cd treatment reduced Hb and increased RDW. The addition of high dose monensin significantly improved erythrocytic indices compared to the control. Erythrocyte anisocytosis was observed in blood smears of Cd-treated mice corresponding to the increased RDW. WBV was significantly elevated in the experimental groups in the whole range of shear rates compared to the control group and in groups 2 and 3 was lower than in group 1 but remained higher compared to group 4. Correlations were found between WBV and RBC, Hb, Hct, MCV and RDW. The results suggest that hemorheological parameters such as WBV should be monitored in parallel with the hematological parameters when monensin is applied and heavy metal intoxication is suspected.

Influence of monensin on cation influx and Na+ -K+ -ATPase activity of Eimeria tenella sporozoites in vitro.

The experiments were conducted to determine intrasporozoite Na+/K+ concentrations (by AAS) and membrane-bound Na+ -K+ -ATPase activity (measured by UV-VIS with a Na+ -K+ -ATPase Detection Kit) of Eimeria tenella sporozoites of the sensitive line (i.e., the parent line, coded as OS) and 2 resistant lines, derived from the parent line (coded as OR125 and OR200), with and without in vitro exposure to monensin. These parameters for OR125 and OR200 were significantly lower than those for OS. In vitro exposure to monensin increased intrasporozoite Na+/K+ concentrations and Na+ -K+ -ATPase activity, but the stimulation on OS was significantly higher than those on OR125 and OR200, indicating that monensin had less effect on resistant parasites. The results of this study suggest that altered biochemical or physiological properties, or both, in the membranes of E. tenella might be related to a reduced sensitivity to monensin.

Susceptibility of Mycobacterium avium sbsp paratuberculosis to monensin sodium or tilmicosin phosphate in vitro and resulting infectivity in a murine model.

This study was designed to determine the susceptibility in vitro and infectivity of 1 field isolate of Mycobacterium avium sbsp paratuberculosis after exposure to monensin sodium and tilmicosin phosphate. Minimum inhibitory concentrations (0.39 microg monensin sodium/mL; 1.60 microg tilmicosin phosphate/mL) were determined in quintuplicate. Organisms were then incubated with 3 different concentrations of each medication for 3 different lengths of time, then washed and resuspended in sterile physiologic saline and injected intraperitoneally into mice that were genetically susceptible to infection. Mice were euthanatized 50 d later and the number of hepatic granulomas was used as the indicator of infectivity. Neither time of incubation nor concentration of medication had any effect on the infectivity of the organisms. Monensin sodium significantly reduced the number of hepatic granulomas in genetically susceptible mice while tilmicosin phosphate did not. Antimycobacterial activity of monensin sodium suggests that the role of monensin in the control of bovine paratuberculosis should be evaluated further.

Effect of monensin sodium on histological lesions of naturally occurring bovine paratuberculosis.

Of 19 adult cows naturally infected with paratuberculosis, 13 were treated with monensin sodium and six remained untreated. At the beginning of the study, the severity of the histological lesions was assessed from biopsy samples of ileum, liver, mesenteric lymph node and rectal mucosa. From the data acquired it was possible to assign the animals so that the lesions in the two groups were similar (P=0. 8323). Monensin was administered in the feed, which contained 147.5 mg/kg, and each treated cow received 450 mg of monensin daily for 120 days. At the end of this period all cows were killed and histopathological findings in the ileum, liver, mesenteric lymph node and rectal mucosa were compared with the initial findings. A scoring system showed that monensin had a beneficial effect in the ileum (P=0.077), liver (P=0.0322) and rectal mucosa (P=0.0578), but under the conditions of the experiment no such effect could be demonstrated in mesenteric lymph node (P=0.3599). There appeared to be an overall effect on all tissues taken together (P=0.1335). The effect of monensin may have been due to both a halting and a reversal of the pathological process. In all but one of the six untreated cows, the lesions worsened during the course of the experiment.

Control of proliferative enteropathy in growing/fattening pigs using growth promoters.

The aim of this study was to evaluate the effect of different antibiotics used as growth promoters on the control of porcine intestinal adenomatosis when administered in weaning, growing and fattening pig diets, according to Annex I of the European Union directive (70/524/EEC and its subsequent amendments to date) for the use of feed additives. On a farm with a previous history of proliferative enteropathy outbreaks, 648 weaned piglets (23 days old) were divided into nine experimental groups according to bodyweight and sex ratio, each group comprising four pens with 18 pigs in each pen. One group served the trial as a negative (unmedicated) control: another (the positive control) received monensin via feed at 100 p.p.m. up to the end of the growing phase (107 days old) and 50 p.p.m. up to slaughter age (156 days old). The remaining seven groups were offered feed with the addition of the following antibiotics: virginia-mycin (50-20 p.p.m.), avilamycin (40-20 p.p.m.), spiramycin (50-20 p.p.m.), zinc bacitracin (50-10 p.p.m.), avoparcin (40-20 p.p.m.), tylosin (40-20 p.p.m.) and salinomycin (60-30 p.p.m.), respectively. The performance of the pigs in the positive control group was very satisfying and among the highest in the trial, verifying earlier field studies. As a general conclusion it seems that all tested growth promoters had a beneficial effect compared with the untreated control, indicated by the decrease of mortality rate, the elimination of diarrhoeal incidence and the enhancement of growth performance, although the proliferative enteropathy control achieved by each substance was not always satisfactory. More specifically, the antibiotic growth promoters tested can be scaled according to their total efficacy as follows: 1. Salinomycin, tylosin, spiramycin; 2. Virginiamycin, zinc bacitracin, avilamycin; and 3. Avoparcin. Finally, it is considered that part of the growth promotion efficacy of the tested substances is due to their potential capacity to control porcine intestinal adenomatosis; thus, in future growth performance trials, the disease background of the trial farms must be examined, especially for porcine enteropathy challenges.

Evaluacion comparativa de triancinolona en el control de coccidiosis en pollos de engorde / Comparative evaluation of triancinolone in coccidiosis control in chickens

La eficacia de Triancinolona en el control de coccidiosis en pollos de engorde fue evaluada en un experimento completamente aleatorizado utilizando pollos sexados Cobb x Cobb de un día de edad. Fueron asignados los tratamientos T1: no medicado - no inoculado; T2: no mediacado - inoculado; T3: Triancinolona - inoculado; T4: Monensina sódica - inoculado y T5: Salinomicina sódica - inoculado. Las aves fueron inoculadas con 10.000 ooquistes de Eimeria tenella y 40.000 de Eimerias intestinales. Los resultados del grado de lesiones mostraron que T3 (60,6 por ciento) y T4 (63,6 por ciento)ejercieron mayor control de la coccidiosis al comparados con T5 (96,9 por ciento) y T2 (100 por ciento). El contaje de ooquistes/g de heces mostró mayor eficacia para T3 (4.300) al comparada con T4 (126.900); T5 (98.100) y T2 (382.000); permitiendo destacar su efectivo mecanismo de acción para interferir el ciclo biológico de las coccidias. La conversión de alimento fue mejorada (P<0,05) en los grupos medicados (T3, T4 y T5) en ralación a T2 destacando el efecto adverso que sobre la respuesta productiva es ocasionado por las coccidias. Triancinolona tuvo mayor eficacia de acción en el control de esta parasitosis.

Interactive effects of betaine and monensin in uninfected and Eimeria acervulina-infected chicks.

Three experiments (Exp.) were conducted to evaluate the interactive effects of dietary betaine (BET) and monensin (MON) in uninfected or Eimeria acervulina-infected chicks. The treatments were replicated with six (Exp. 1) or five (Exp. 2 and 3) pens of five chicks each. The experimental periods lasted 9 (Exp. 1 and 2) or 10 (Exp. 3) d each and the coccidiosis infections were established on Day 2 (Exp. 1 and 2) or Day 3 (Exp. 3) of the experiment. Average initial weight of the chicks was 101, 73, and 68 g in Exp. 1 to 3, respectively, and the initial age of the chicks was 5 (Exp. 1) or 4 (Exp. 2 and 3) d. A corn-soybean meal basal diet was used in each experiment. In Exp. 1, the effect of dietary BET (0, 0.1, or 0.5%) in uninfected or coccidiosis-infected (COC; 5 x 10(5) sporulated E. acervulina oocysts) chicks was investigated. In Exp. 2, the interactive effects of BET (0 or 0.1%) and MON (0 or 55 ppm) in uninfected or COC chicks were investigated in a 2 x 2 x 2 factorial arrangement of treatments. Experiment 3 was identical to Exp. 2, except the level of MON was 110 rather than 55 ppm. In Exp. 1, 2, and 3, COC reduced (P < 0.01) gain, feed intake (FI), feed efficiency (GF), and plasma carotenoid concentration (CAR) and increased (P < 0.01) lesion score (LS). In Exp. 1, gain and FI were decreased in uninfected chicks fed 0.1% BET but gain and FI were increased in COC chicks fed 0.1% BET (COC x BET quadratic, P < 0.01). Dietary BET linearly increased (P < 0.05) GF. In Exp. 2 and 3, MON increased (P < 0.01) gain, FI, GF, and CAR and decreased (P < 0.01) LS of COC chicks, but MON had no effect in uninfected chicks (COC x MON, P < 0.01). In Exp. 2, GF was increased more in chicks fed both MON and BET than in chicks fed MON (BET x MON, P < 0.06). In Exp. 3, BET increased GF of uninfected chicks fed MON and of COC chicks not fed MON (COC x BET x MON, P < 0.02). Betaine may have an effect on E. acervulina-infected chicks, but there is no conclusive evidence to indicate that the efficacy of MON is improved when fed in combination with BET.