RESUMEN
Two experiments were designed to evaluate the impacts of supplementing lasalocid (LAS), narasin (NAR), or virginiamycin (VRM) on rumen fermentation parameters, apparent nutrient digestibility, and blood parameters (Exp. 1), as well as feed intake and performance (Exp. 2) of Nellore cattle consuming a forage-based diet. In Exp. 1, 32 rumen-fistulated Nellore steers (initial shrunk body weight [BW] = 355 ± 4.4 kg) were assigned to a randomized complete block design. Within block, animals were randomly assigned to one of four treatments: 1) forage-based diet without feed additives (CON), 2) CON diet plus 13 mg/kg of dry matter (DM) of NAR, 3) CON diet plus 20 mg/kg of DM of sodium LAS, or 4) CON diet plus 20 mg/kg of DM of VRM. No treatment effects were detected (P ≥ 0.32) for intake and apparent digestibility of nutrients. Steers fed NAR had the lowest (P ≤ 0.01) molar proportion of acetate on day 28, 56, and 112 vs. CON, LAS, and VRM steers, whereas acetate did not differ (P ≥ 0.25) between LAS, VRM, and CON steers from day 28 to 84. On day 112, steers fed LAS had a lower (P < 0.02) molar proportion of acetate vs. VRM and CON, whereas it did not differ between CON and VRM (P > 0.33). Steers receiving NAR had a greater (P ≤ 0.04) ruminal propionate vs. CON, LAS, and VRM, whereas LAS steers had greater (P < 0.04) propionate vs. CON and VRM steers on day 28 and 112, and it did not differ (P > 0.22) between CON and VRM. In Exp. 2, 160 Nellore bulls were blocked by initial shrunk BW (212 ± 3.1 kg) in a 140-d feedlot trial. Diets contained the same treatments used in Exp. 1. Bulls fed NAR had greater (P < 0.02) average daily gain (ADG) vs. CON and VRM, and similar (P = 0.17) ADG between NAR and LAS, whereas ADG did not differ (P > 0.28) between LAS, VRM, and CON bulls. A treatment effect was detected (P = 0.03) for dry matter intake, being greater in NAR vs. CON, LAS, and VRM bulls, and similar (P > 0.48) between CON, LAS, and VRM bulls. A tendency was detected (P = 0.09) for feed efficiency, which was greater (P < 0.02) in NAR bulls vs. CON and VRM, and similar (P = 0.36) between NAR and LAS bulls. From day 112 to 140, bulls receiving NAR were heavier (P < 0.03) vs. CON, LAS, and VRM bulls, but no differences were observed (P > 0.51) between CON, LAS, and VRM bulls. Collectively, ruminal fermentation profile and intake were impacted by NAR supplementation, which partially contributed to the enhanced performance of Nellore bulls receiving a forage-based diet.
Feed additives are nutritional tools that benefit dietary digestibility and nutrient utilization, alter ruminal fermentation routes, and improve cattle growth and efficiency, thus increasing productivity and profitability in beef cattle systems. Nonetheless, most of the current research focuses on supplementing feed additives in high-concentrate diets. Leaving a significant gap in understanding the influence of feed additives in cattle consuming forage-based diets, especially molecules capable of altering the fermentation process and, consequently, beef cattle performance. Therefore, this experiment aimed to evaluate the impacts of supplementing narasin (NAR), lasalocid (LAS), or virginiamycin (VRM) on rumen fermentation parameters, apparent nutrient digestibility, feed intake, and performance of Bos indicus Nellore cattle consuming a forage-based diet. Including commercially available feed additives into forage-based diets did not impact nutrient intake and digestibility of nutrients. The inclusion of NAR affected ruminal fermentation parameters toward propionate production, positively contributing to animal performance. Ruminal fermentation characteristics and animal growth were not impacted by dietary LAS and VRM, which could be attributed to the dose used in the current experiment, despite the manufacturer's recommendation. This research provides insights into NAR as an important feed additive for forage-based beef cattle diets.
Asunto(s)
Suplementos Dietéticos , Lasalocido , Bovinos , Animales , Masculino , Lasalocido/farmacología , Propionatos/metabolismo , Rumen/metabolismo , Alimentación Animal/análisis , Digestión , Dieta/veterinaria , Peso Corporal , FermentaciónRESUMEN
This study aimed to investigate the comparison of effect of anticoccidal drugs including lasalocid and diclazuril with probiotic and synbiotic on the growth performance and intestinal morphology in broiler chicken. One hundred eighty chickens (Ross 308, 1 day old) were randomly divided into 6 equal groups (n=30) including the negative control (basal diet), the positive control (basal diet+oral inoculation of 3×104 sporulated oocytes of E. tenella, and four treatment groups. At days of 28 and 49 of age, 9 chickens were blindly chosen from each group were scarified by decapitation and their various segments of small intestine including ileum, jejunum, and duodenum were evaluated histomorphologically. We found that the economic losses resulted from coccidial infection in the poultry industry are caused by the decreased performance of broiler chicken induced by morphological changes in the any three segments specially jejunum. The anticoccidial drugs, synbiotic and probiotic can partially prevent morphological changes in any three segments of small intestine in broiler chicken with coccidiosis. Since morphological changes in the jejunum begin earlier than in other parts and surface area of jejunal villi is important for nutrition absorbance as well as growth performance, lasolacid was found to a be more efficient treatment in this regard.
Asunto(s)
Coccidiostáticos , Nitrilos , Enfermedades de las Aves de Corral , Probióticos , Triazinas , Animales , Lasalocido/farmacología , Lasalocido/uso terapéutico , Coccidiostáticos/farmacología , Coccidiostáticos/uso terapéutico , Pollos , Probióticos/farmacología , Intestino Delgado , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/tratamiento farmacológicoRESUMEN
The study aimed to examine the effect of simultaneous application of florfenicol and lasalocid on the performance and vital organ function of chickens. For this, 300 chicks were divided into four groups. Group one to three received florfenicol, lasalocid and lasalocid plus florfenicol, respectively. Group four as the control group received a basic diet without lasalocid or florfenicol. Lasalocid was used from 7 to 35 days old, continuously. Florfenicol was used at 21 days old for 5 days. The growth indices were measured at the end of each week. The chickens were euthanized at the ages of 28 and 35 days old after collecting blood samples with and without anticoagulants. The liver, heart, muscle, kidney and sciatic nerve were collected in formalin 10% for histopathological examination. The blood and serum samples were used to determine clinical pathologic and hematologic indices. The ratio of internal organs to body weight and ratio of the right ventricle to the total ventricles (RV/TV) of the heart was measured. Results showed, the use of lasalocid decreased feed conversion rate and triglyceride, and increased total protein. Simultaneous administration of lasalocid and florfenicol affected histopathology of the liver and heart and significantly increased creatine phosphokinase, uric acid and the ratio of RV/TV of heart. The eosinophil percentage in the chickens who received florfenicol plus lasalocid was significantly higher than chickens who received florfenicol alone (p < 0.05). In conclusion, it seems that simultaneous administration of the florfenicol and lasalocid induces side-effects especially on cardiac function and it is not recommended.
Asunto(s)
Pollos , Lasalocido , Alimentación Animal/análisis , Animales , Riñón , Lasalocido/farmacología , Hígado , Miocardio , Nervio Ciático , Tianfenicol/análogos & derivadosRESUMEN
The ionophore lasalocid is widely used as a veterinary drug against coccidiosis. We found recently that lasalocid protects cells from two unrelated bacterial toxins, the cytotoxic necrotizing factor-1 (CNF1) from Escherichia. coli and diphtheria toxin. We evaluated lasalocid's capacity to protect cells against other toxins of medical interest comprising toxin B from Clostridium difficile, Shiga-like toxin 1 from enterohemorrhagic E. coli and exotoxin A from Pseudomonas aeruginosa. We further characterized the impact of lasalocid on the endolysosomal and the retrograde pathways and organelle integrity, especially the Golgi apparatus. We found that lasalocid protects cells from all toxins tested and impairs the drop of vesicular pH along the trafficking pathways that are required for toxin sorting and translocation to the cytoplasm. Lasalocid also has an impact on the cellular distribution of GOLPH4 and GOLPH2 Golgi markers. Other intracellular trafficking compartments positive for EEA1 and Rab9A display a modified cellular pattern. In conclusion, lasalocid protects cells from multiple deadly bacterial toxins by corrupting vesicular trafficking and Golgi stack homeostasis.
Asunto(s)
Toxinas Bacterianas/toxicidad , Lasalocido/farmacología , Sustancias Protectoras/farmacología , Transporte Biológico , Toxina Diftérica , Endosomas , Escherichia coli , Exotoxinas , Aparato de Golgi , Humanos , Ionóforos , Lisosomas , Toxina Shiga IRESUMEN
Lasalocid, a specific mobile membrane ionophore for calcium, dopamine and norepinephrine was assayed in its capacity to reduce or maintain unaltered the cardiovascular function in conditions of imminent myocardial injury. In experiments of coronary blockade and reperfusion carried out in rat heart, it was found that when administered from 5 to 30 minutes prior to the induction of coronary blockade, at a concentration of 2 mg/kg of body weight, the ionophore immediately, simultaneously, and completely interrupts the blood pressure decay, cardiac frequency increase, electrical ventricular tachycardia and fibrillation, as well as the fall of mitochondrial oxidative phosphorylation and decay of mitochondrial oxygen uptake provoked by the induced myocardial injury. It appears that the molecular mode of action of the lasalocid is associated with its unique ability to transport both calcium and the catecholamines, dopamine and norepinephrine, across mitochondrial and bimolecular lipid membranes, as well as through synaptic cell membrane terminals from rat heart, myocardial fibers of the heart and heart chromaffin membrane vesicles. It is suggested that for the potential medical use of lasalocid to detain incoming ischemic myocardial damage, there exists a need to develop a personal electronic device able to simultaneously monitor, detect, and inform on the very early and simultaneous signs of cardiac alterations of electrical, mechano-chemical, metabolic and hydraulic nature, all which precede heart failure and to administer the lasalocid.
Asunto(s)
Corazón/parasitología , Lasalocido/farmacología , Mitocondrias Cardíacas , Daño por Reperfusión Miocárdica , Miocardio , Animales , Masculino , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/patología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/fisiopatología , Daño por Reperfusión Miocárdica/prevención & control , Miocardio/metabolismo , Miocardio/patología , Ratas , Ratas WistarRESUMEN
Cytotoxic necrotizing factorâ 1 (CNF1) is a toxin produced by pathogenic strains of Escherichia coli responsible for extra-intestinal infections. CNF1 deamidates Rac1, thereby triggering its permanent activation and worsening inflammatory reactions. Activated Rac1 is prone to proteasomal degradation. There is no targeted therapy against CNF1, despite its clinical relevance. In this work we developed a fluorescent cell-based immunoassay to screen for inhibitors of CNF1-induced Rac1 degradation among 1120 mostly approved drugs. Eleven compounds were found to prevent CNF1-induced Rac1 degradation, and five also showed a protective effect against CNF1-induced multinucleation. Finally, lasalocid, monensin, bepridil, and amodiaquine protected cells from both diphtheria toxin and CNF1 challenges. These data highlight the potential for drug repurposing to fight several bacterial infections and Rac1-based diseases.
Asunto(s)
Toxinas Bacterianas/antagonistas & inhibidores , Proteínas de Escherichia coli/antagonistas & inhibidores , Bibliotecas de Moléculas Pequeñas/farmacología , Proteína de Unión al GTP rac1/metabolismo , Amodiaquina/farmacología , Toxinas Bacterianas/efectos adversos , Toxinas Bacterianas/metabolismo , Bepridil/farmacología , Toxina Diftérica/efectos adversos , Reposicionamiento de Medicamentos , Escherichia coli/química , Proteínas de Escherichia coli/efectos adversos , Proteínas de Escherichia coli/metabolismo , Células HeLa , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inmunoensayo , Lasalocido/farmacología , Monensina/farmacología , Proteína de Unión al GTP rac1/química , Proteína de Unión al GTP rac1/inmunologíaRESUMEN
Chemotherapeutic treatment of human and animal trypanosomiasis is unsatisfactory because only a few drugs are available. As these drugs have poor efficacy and cause adverse reactions, more effective and tolerable medications are needed. As the polyether ionophore antibiotic lasalocid acid is used as medicated feed additive in cattle, the compound was tested for its trypanocidal and cytotoxic activity against bloodstream forms of Trypanosoma brucei and human myeloid HL-60 cells. The concentrations required of lasalocid acid to reduce the growth rate of trypanosomes by 50% and to kill the parasites were 1.75 and 10 µM, respectively. The ionophore displayed also cytotoxic activity against HL-60 cells but the human cells were about 10 to 14 times less sensitive indicating moderate selectivity. As the trypanocidal mechanism of action of polyether ionophore antibiotics is due to a sodium influx-induced cell swelling, the effect of lasalocid acid on cell volume change in bloodstream-form trypanosomes was investigated. Interestingly, lasalocid acid induced a much faster cell swelling in trypanosomes than the more trypanocidal related ionophore salinomycin. These results support further investigations of lasalocid acid and derivatives thereof as potential agents against African trypanosomiasis.
Asunto(s)
Tamaño de la Célula/efectos de los fármacos , Lasalocido/farmacología , Tripanocidas/farmacología , Trypanosoma brucei brucei/efectos de los fármacos , Tripanosomiasis Africana/tratamiento farmacológico , Animales , Bovinos , Línea Celular Tumoral , Células HL-60 , Humanos , Ionóforos/farmacología , Piranos , Tripanosomiasis Africana/parasitologíaRESUMEN
Our hypothesis was that increasing the inclusion level of dried distiller's grains with solubles (DDGS) to feedlot lambs would increase growth and the inclusion of lasalocid (LAS; Bovatec, Alpharma, LLC, Bridgewater, NJ) would increase ADG and G:F, while not affecting digestibility, ruminal VFA concentration, and ruminal pH. Furthermore, we hypothesized that rations containing LAS and higher levels of DDGS would cause increased ruminal hydrogen sulfide gas (HS) concentrations. Two hundred forty crossbred (Suffolk × Rambouillet) lambs (31.9 ± 5.87 kg BW; approximately 90 d of age) were allocated to 6 treatments in a completely randomized design with a 3 × 2 factorial arrangement of treatments. Lambs were placed into 24 feedlot pens (4 pens/treatment; 10 lambs/pen) for a 111 d finishing study. Main effects included concentration of DDGS (0, 15, or 30% DM basis) and inclusion of LAS (0 or 22.05 g/metric ton LAS) resulting in treatments of: 1) 0% DDGS without LAS (0DDGS-NL), 2) 0% DDGS with LAS (0DDGS-L), 3) 15% DDGS without LAS (15DDGS-NL), 4) 15% DDGS with LAS (15DDGS-L), 5) 30% DDGS without LAS (30DDGS-NL), and 6) 30% DDGS with LAS (30DDGS-L). Two-day weights were taken at the beginning and end of the experiment. Two-hundred-eighteen lambs (64.8 ± 7.99 kg BW) were slaughtered on d 112 at a commercial abattoir and carcass data collected. The inclusion of LAS increased ( ≤ 0.02) final BW, ADG, G:F, and HCW. As DDGS in the ration increased to 30%, DMI decreased linearly ( = 0.03) while G:F increased linearly ( = 0.03). A second study was conducted utilizing the same treatments to evaluate N and S balance, ruminal VFA and H2S concentration, and ruminal pH in 24 crossbred wethers (Suffolk × Rambouillet; 41.2 ± 12.23 kg BW). Daily urinary sulfur excretion and ruminal H2S concentration were linearly increased ( < 0.001) as DDGS increased in the ration. Total ruminal VFA concentration linearly decreased ( = 0.002) as DDGS increased in the ration. The inclusion of LAS increased ( = 0.02) ruminal pH. The results confirm our hypothesis that LAS increased overall growth and increasing DDGS increased ruminal HS concentration but did not influence growth. We reject the hypothesis that the combined effects of LAS and DDGS would have no effect on rumen pH and VFA concentrations.
Asunto(s)
Alimentación Animal/análisis , Composición Corporal/efectos de los fármacos , Dieta/veterinaria , Lasalocido/farmacología , Rumen/efectos de los fármacos , Ovinos/crecimiento & desarrollo , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Líquidos Corporales , Suplementos Dietéticos , Digestión/efectos de los fármacos , Grano Comestible , Ácidos Grasos Volátiles/química , Ácidos Grasos Volátiles/metabolismo , Sulfuro de Hidrógeno/química , Sulfuro de Hidrógeno/metabolismo , MasculinoRESUMEN
Lasalocid is an antibiotic from the group of carboxylic ionophores, produced by Streptomyces lasaliensis. But there was limited information of lasalocid on human prostate cancer cells. In the present studies, to better understand its effect in human prostate cancer cells, apoptosis and autophagy associated with possible signal pathways in vitro was examined. Our study showed that lasalocid mediated cell cycle arrest in G0/G1 phase by reducing G1 phase dependent proteins, indicating entering into apoptotic cell death pathway. Lasalocid-induced apoptosis was involved with reactive oxygen species (ROS) production, and mitochondrial hyperpolarization. In addition, lasalocid induced autophagy through microtubule-associated protein 1 light chain 3 (LC-3)-II conversion, acidic vesicular organelles formation and GFP-LC-3 punctuate, which was inhibited by 3-methyladenine (3-MA), a widely used pharmacological inhibitor of autophagy. Furthermore, the autophagic phenomena were mediated by production of ROS, confirming that inhibition of ROS with N-acetyl-l-cysteine, a ROS inhibitor, attenuated lasalocid-triggered autophagy. Inhibition of autophagy with 3-MA enhanced the lasalocid-induced apoptosis through enhanced ROS generation. Taken together, lasalocid should be useful in the search for new potential chemotherapeutic agents for understanding the molecular mechanisms of anticancer in prostate cancer cells.
Asunto(s)
Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Lasalocido/farmacología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , MasculinoRESUMEN
The cell wall is one major determinant of plant cell morphology, and is an attractive bioresource. Here, we report a novel strategy to modify plant cell wall property by small molecules. Lasalocid sodium (LS) was isolated by chemical screening to identify molecules that affect the cell morphology of tobacco BY-2 cells. LS treatment led to an increase in cell wall thickness, whilst the quantity and sugar composition of the cell wall remained unchanged in BY-2 cells. The chemical also disordered the cellular arrangement of hypocotyls of Arabidopsis plants, resulting in a decrease in hypocotyl length. LS treatment enhanced enzymatic saccharification efficiency in both BY-2 cells and Arabidopsis plants. Microarray analysis on Arabidopsis showed that exposure to LS upregulated type III peroxidase genes, of which some are involved in lignin biogenesis, and jasmonic acid response genes, and phloroglucinol staining supported the activation of lignification by the LS treatment. As jasmonic acid-mediated lignification is a typical reaction to cell wall damage, it is possible that LS induces cell wall loosening, which can trigger cell wall damage response. Thus, LS is a unique chemical for modification of cell wall and morphology through changes in cell wall architecture.
Asunto(s)
Arabidopsis/metabolismo , Pared Celular/metabolismo , Hipocótilo/crecimiento & desarrollo , Lasalocido/farmacología , Nicotiana/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/biosíntesis , Pared Celular/genética , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Hipocótilo/genética , Células Vegetales/metabolismo , Nicotiana/genéticaRESUMEN
The effects of lasalocid on rumen measures, beef and dairy performance, and carcass traits were evaluated using meta-analysis. Meta-regression was used to investigate sources of heterogeneity. Ten studies (20 comparisons) were used in the meta-analysis on rumen measures. Lasalocid increased total VFA and ammonia concentrations by 6.46 and 1.44 m, respectively. Lasalocid increased propionate and decreased acetate and butyrate molar percentage (M%) by 4.62, 3.18, and 0.83%, respectively. Valerate M% and pH were not affected. Meta-regression found butyrate M% linearly increased with duration of lasalocid supplementation (DUR; = 0.017). When >200 mg/d was fed, propionate and valerate M% were higher and acetate M% was lower ( = 0.042, = 0.017, and = 0.005, respectively). Beef performance was assessed using 31 studies (67 comparisons). Lasalocid increased ADG by 40 g/d, improved feed-to-gain ratio (F:G) by 410 g/kg, and improved feed efficiency (FE; combined measure of G:F and the inverse of F:G). Lasalocid did not affect DMI, but heterogeneity in DMI was influenced by DUR ( = 0.004) and the linear effect of entry BW ( = 0.011). The combination of ≤100 vs. >100 d DUR and entry BW ≤275 vs. >275 kg showed that cattle ≤275 kg at entry fed lasalocid for >100 d had the lowest DMI. Heterogeneity of ADG was influenced by the linear effect of entry BW ( = 0.028) but not DUR. Combining entry BW ≤275 vs. >275 kg and DUR showed that cattle entering at >275 kg fed ≤100 d had the highest ADG. The FE ( = 0.025) and F:G ( = 0.015) linearly improved with dose, and entry BW >275 kg improved F:G ( = 0.038). Fourteen studies (25 comparisons) were used to assess carcass traits. Lasalocid increased HCW by 4.73 kg but not dressing percentage, mean fat cover, or marbling score. Heterogeneity of carcass traits was low and not affected by DUR or dose. Seven studies (11 comparisons) were used to assess dairy performance but the study power was relatively low and the evidence base is limited. Lasalocid decreased DMI in total mixed ration-fed cows by 0.89 kg/d but had no effect on milk yield, milk components, or component yields. Dose linearly decreased DMI ( = 0.049). The DUR did not affect heterogeneity of dairy measures. This work showed that lasalocid improved ADG, HCW, FE, and F:G for beef production. These findings may reflect improved energy efficiency from increased propionate M% and decreased acetate and butyrate M%. Large dairy studies are required for further evaluation of effects of lasalocid on dairy performance.
Asunto(s)
Composición Corporal/efectos de los fármacos , Bovinos , Lasalocido/farmacología , Rumen/efectos de los fármacos , Alimentación Animal/análisis , Animales , Antibacterianos/farmacología , Butiratos , Suplementos Dietéticos , Femenino , Leche/química , Fenotipo , Rumen/fisiologíaRESUMEN
Campylobacter bacteria are foodborne pathogens that can colonize the gut of food animals. Limited in their ability to ferment sugars, Campylobacter can derive energy for growth via amino acid catabolism. The objectives of the present studies were to test whether supplemental distillers grains containing high amounts of rumen-undegradable intake protein or supplemental lasalocid may, by promoting amino acid flow to the lower bovine gut, increase intestinal carriage of Campylobacter. In study one, 10 steers (5 per treatment) were adapted to diets formulated to achieve 0 or 30% dried distillers grains. After an initial 14-day adaptation to the basal diet, control and treated steers were fed their respective diets for 23 days, after which time they were fed supplemental lasalocid for an additional 8 days, followed by a 5-day withdrawal. In study two, 24 steers preacclimated to a basal diet were adapted via 3-day periodic increases to dietary treatments formulated to achieve 0, 30, or 60% wet corn distillers grains with solubles. Analysis of Campylobacter bacteria cultured from duodenal and fecal samples in study one and from fecal samples in study two revealed no effect of dried distillers grains or wet corn distillers grains with solubles on the prevalence or concentrations of duodenal or fecal Campylobacter. The results from study one indicated that colonized steers, regardless of treatment, harbored higher Campylobacter concentrations when transitioned to the basal diet than when coming off pasture. Campylobacter carriage was unaffected by lasalocid. These results provide no evidence that feeding distillers grains high in rumen-undegradable intake protein or supplemental lasalocid contributes to increased intestinal carriage of Campylobacter in fed cattle.
Asunto(s)
Alimentación Animal/análisis , Campylobacter/crecimiento & desarrollo , Bovinos/microbiología , Lasalocido/análisis , Zea mays/química , Animales , Antibacterianos/análisis , Antibacterianos/farmacología , Campylobacter/efectos de los fármacos , Bovinos/metabolismo , Dieta/veterinaria , Heces/microbiología , Tracto Gastrointestinal/microbiología , Lasalocido/farmacologíaRESUMEN
In this study, the effect of probiotic supplementation via drinking water or feed on the performance of broiler chickens experimentally infected with sporulated oocysts of Eimeria acervulina (5 × 10(4)), Eimeria maxima and Eimeria tenella (2 × 10(4) each one) at 14 days of age was evaluated. Two hundred and forty 1-day-old Ross 308 male chicks were separated into eight equal groups with three replicates. Two of the groups, one infected with mixed Eimeria oocysts and the other not, were given a basal diet and served as controls. The remaining groups were also challenged with mixed Eimeria species and received the basal diet and either water supplemented with probiotic (three groups) or probiotic via feed (two groups); the probiotic used consisted of Enterococcus faecium #589, Bifidobacterium animalis #503 and Lactobacillus salivarius #505 at a ratio of 6:3:1. Probiotic supplementation was applied either via drinking water in different inclusion rates (groups W1, W2 and W3) or via feed using uncoated (group FN) or coated strains (group FC). The last group was given the basal diet supplemented with the anticoccidial lasalocid at 75 mg/kg. Each experimental group was given the corresponding diet or drinking water from day 1 to day 42 of age. Throughout the experimental period of 42 days, body weight and feed intake were recorded weekly and feed conversion ratios were calculated. Seven days after infection, the infected control group presented the lowest weight gain values, while probiotics supplied via feed supported growth to a comparable level with that of the lasalocid group. Probiotic groups presented lesion score values and oocyst numbers that were lower than in control infected birds but higher than in the lasalocid group. In the duodenum, jejunum and ileum, the highest villous height values were presented by probiotic groups. In conclusion, a mixture of probiotic substances gave considerable improvement in both growth performance and intestinal health in comparison with infected control birds and fairly similar improvement to an approved anticoccidial during a mixed Eimeria infection.
Asunto(s)
Pollos/crecimiento & desarrollo , Coccidiosis/veterinaria , Coccidiostáticos/farmacología , Eimeria/fisiología , Probióticos/farmacología , Alimentación Animal , Animales , Bifidobacterium , Pollos/parasitología , Coccidiosis/tratamiento farmacológico , Coccidiosis/patología , Suplementos Dietéticos , Enterococcus faecium , Heces/parasitología , Intestinos/patología , Lactobacillus , Lasalocido/farmacología , Oocistos , Enfermedades de las Aves de Corral/tratamiento farmacológico , Enfermedades de las Aves de Corral/parasitología , Enfermedades de las Aves de Corral/patología , Agua , Aumento de PesoRESUMEN
Seven Mannich base derivatives of polyether antibiotic Lasalocid acid (2a-2g) were synthesized and screened for their antiproliferative activity against various human cancer cell lines. A novel chemoselective one-pot synthesis of these Mannich bases was developed. Compounds 2a-2c and 2g with sterically smaller dialkylamine substituent, displayed potent antiproliferative activity (IC50: 3.2-7.3 µM), and demonstrated higher than twofold selectivity for specific type of cancer. The nature of Mannich base substituent on C-2 atom at the aromatic ring may be critical in the search for selectivity towards a particular cancer cell.
Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Lasalocido/análogos & derivados , Lasalocido/farmacología , Bases de Mannich/química , Antibacterianos/química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HT29 , Humanos , Lasalocido/síntesis química , Lasalocido/química , Células MCF-7 , Conformación Molecular , Relación Estructura-ActividadRESUMEN
We evaluated the effects of dietary supplementation with different preparations of probiotics on the performance of broiler chickens experimentally infected with 2 × 10(4) sporulated oocysts of Eimeria tenella at 14 days of age. Three hundred, day-old, Cobb-500 chicks, as hatched, were separated into 10 equal groups with three replicates. Two of the groups, one challenged with E. tenella oocysts and the other not, were given a basal diet and served as controls without medication. The other challenged groups were given the anticoccidial lasalocid (60 mg/kg) or Enterococcus faecium (5 × 10(8) or 5 × 10(9)cfu/kg feed), Bifidobacterium animalis (5 × 10(8)cfu/kg feed), Lactobacillus reuteri (5 × 10(8)cfu/kg feed), Bacillus subtilis (5 × 10(8)cfu/kg feed), or a multi-species probiotic mix at 5 × 10(8) or 5 × 10(9)cfu/kg feed, respectively. The trial lasted 6 weeks. Individual body weight, feed intake per pen and feed conversion ratio values were recorded weekly, along with the extent of bloody diarrhea, excreta oocyst numbers and bird mortality. Caecal lesions were assessed and intestinal samples were taken for histopathological and bacteriological evaluation from ileum and caecum. Overall growth performance of chickens fed the multi-species probiotic mix at both levels was higher (P<0.05) compared to the infected control. Overall oocyst shedding was lowest (P<0.05) in the lasalocid supplemented group. Villous height was higher (P<0.05) in Bacillus supplemented groups compared to infected controls. The Lactobacillus supplemented group had the highest (P<0.05) numbers of both Lactobacillus and Bifidobacterium in ileum and caecum. In conclusion, dietary probiotics are promising for further investigation on improving intestinal health and growth performance of broiler chickens experimentally challenged with E. tenella.
Asunto(s)
Pollos , Suplementos Dietéticos , Eimeria tenella , Intestinos/efectos de los fármacos , Enfermedades de las Aves de Corral/prevención & control , Probióticos/farmacología , Animales , Bacterias/clasificación , Pollos/crecimiento & desarrollo , Coccidiosis/parasitología , Coccidiosis/prevención & control , Coccidiosis/veterinaria , Femenino , Intestinos/microbiología , Intestinos/parasitología , Lasalocido/farmacología , MasculinoRESUMEN
Avaliou-se o desempenho de 25 novilhos Holandês x Zebu, castrados, com média de peso vivo inicial de 265±50 kg, sob pastejo emBrachiaria decumbens, distribuídos em cinco grupos e em cinco piquetes, segundo os tratamentos: controle - suplementação múltipla sem ionóforos (CONT); suplementação múltipla com 100mg/cab/dia de monensina (M100); suplementação múltipla com 200mg/cab/dia de monensina (M200); suplementação múltipla com 100mg/cab/dia de lasalocida (L100); suplementação múltipla com 200mg/cab/dia de lasalocida (L200). O período experimental foi de 105 dias, com rotação dos grupos nos piquetes a cada 21 dias. A suplementação foi fornecida ad libitum. A avaliação de desempenho ocorreu mediante a pesagem dos animais, em jejum de alimento e água de 14 horas, no início de cada período e término do experimento. Os animais alimentados com suplementos com ionóforos apresentaram maior ganho de peso em relação aos do controle (0,357 vs. 0,268; P = 0,0068). Entre os ionóforos, os animais alimentados com lasalocida ganharam mais peso (0,398 vs. 0,333; P=0,0175). O melhor desempenho pode ser explicado pelo maior consumo dos suplementos pelos animais alimentados com lasalocida (0,53 vs. 0,42; P<0,0001).
The performance of 25 castrated Holstein x Zebu crossbred steers averaging 265±50kgBW, grazing on Brachiaria decumbens, during dry season was evaluated. The experiment was carried out in a completed randomized design and the animals were grouped in five different paddocks with the following treatments: control - multiple supplement without ionophores (CONT); multiple supplement with 100mg of monensin/animal/day (M100); multiple supplement with 200mg of monensin/animal/day (M200); multiple supplement with 100mg of lasalocid/animal/day (L100); and multiple supplement with 200mg of lasalocid/animal/day (L200). The experimental period was 105 days, with changing groups on paddocks every 21 days. The multiple supplement was offered ad libitum. Body weight was evaluated after 14 hours of fasting. Animals fed multiple supplement with ionophores showed higher average daily weight gain than control (0.357 vs 0.268; P= 0.0068), as well as steers fed lasalocid in comparision to monensin (0.398 vs. 0.333; P= 0.0175). Animals suplemented with lasalocid had higher intakes and higher average daily gain (0.53 vs. 0.42; P<0.0001).
Asunto(s)
Animales , Bovinos/clasificación , Suplementos Dietéticos/análisis , Ayuno/metabolismo , Lasalocido/farmacología , Peso Corporal/fisiologíaRESUMEN
Avaliou-se o efeito do suplemento múltiplo com ionóforos sobre o consumo, a fermentação ruminal e a degradabilidade in situ da matéria seca da forragem. Utilizaram-se cinco novilhos Holandês x Zebu fistulados no rúmen, com peso vivo médio de 350kg, em delineamento em quadrado latino. Os tratamentos foram: suplementação múltipla sem ionóforos (CONT); suplementação múltipla com 100mg/cab/dia de monensina (M100); suplementação múltipla com 200mg/cab/dia de monensina (M200); suplementação múltipla com 100mg/cab/dia de lasalocida (L100); e suplementação múltipla com 200mg/cab/dia de lasalocida (L200). O uso de ionóforos no suplemento não influenciou o consumo de forragem, que foi, em média, 7,24kg MS/dia. A presença de ionóforos resultou em ligeiro aumento do pH ruminal em relação à ausência desses aditivos (P<0,05). Houve diferença na concentração do N-NH3 apenas para os teores de ionóforos em que 200mg/cab/dia reduziu a quantidade de N-NH3. As concentrações de acetato, propionato e butirato não foram influenciadas pela inclusão, pelo tipo ou pelos teores de ionóforos. A fração solúvel média (A) da Brachiaria decumbens foi igual a 22 por cento, e a fração insolúvel potencialmente degradável média (B) igual a 65 por cento, resultando em degradação potencial média de 87 por cento. A taxa de degradação média (c) foi de 0,03/hora. Os ionóforos não alteraram a degradação in situ da matéria seca.
The effect of multiple supplement with ionophores was evaluated on intake, ruminal fermentation, and in situ degradability of dry matter (DM) of the pasture forage. Five rumen fistulated Holstein x Zebu steers averaging 350kg of BW were used. The animals were grouped in five different paddocks under Latin Square experimental design. The treatments were multiple supplement without ionophores (CONT); multiple supplement with 100mg of monensin/animal/day (M100); multiple supplement with 200mg of monensin/animal/day (M200); multiple supplement with 100mg of lasalocid/animal/day (L100); multiple supplement with 200mg of lasalocid/animal/day (L200). The pasture intake was 7.24kg DM/day and it was not affected by ionophores. The average pH was influenced (P<0.05) by the presence of the ionophores in the supplements. There rumen N-NH3 concentration was negatively influenced by the ionophores levels in the multiple supplement. The molar concentrations of acetate, propionate, and butirate in the rumen were not affect by the presence, type, or level of ionophores. The mean soluble fraction A of Brachiaria decumbens was 22 percent, the mean potential degradable insoluble fraction (B) was 65 percent, and the degradability was 87 percent. The mean degradation rate (c) was 0.03/h. The ionophores did not affect DM in situ degradability.
Asunto(s)
Animales , Bovinos/clasificación , Suplementos Dietéticos/análisis , Fermentación , Ionóforos/química , Lasalocido/farmacologíaRESUMEN
A lactic-acid producing bacterium was isolated from the rumen of lambs with rumen acidosis. The cells were gram-positive, nonmotile, nonsporing, catalase negative spherical, 1.5-2.0 µm in diameter, and occur in pairs and tetrads. Analysis of 16S ribosomal RNA indicated that the rumen bacterium was a strain of Pediococcus acidilactici with 99% of nucleotide homology. This bacterium was sensible to monensin and lasalocid at the unique dose tested of 300 ppm. The concentration of lactic acid and DM degradation decreased (P<0.05) when monensin or lasalocid were added to the culture media after 24, 48 and 72 h of incubation. In contrast, total VFA concentration and pH were higher (P<0.05) in the culture media added with the ionophores. Up to now S. bovis is considered the main ruminal bacterium related with rumen acidosis, but the importance of P. acidilactici should be also reconsidered in experimental studies focused on the control rumen acidosis.
Asunto(s)
Acidosis/veterinaria , Lasalocido/farmacología , Monensina/farmacología , Pediococcus/aislamiento & purificación , Rumen/microbiología , Enfermedades de las Ovejas/inducido químicamente , Alimentación Animal/análisis , Alimentación Animal/toxicidad , Animales , Antibacterianos/farmacología , Dieta/veterinaria , Carbohidratos de la Dieta/análisis , Carbohidratos de la Dieta/toxicidad , Resistencia a Medicamentos , Historia del Siglo XVI , Concentración de Iones de Hidrógeno , Ionóforos/farmacología , Masculino , Pediococcus/clasificación , Pediococcus/efectos de los fármacos , Pediococcus/genética , Filogenia , ARN Ribosómico 16S/genética , OvinosRESUMEN
Six ruminally fistulated midlactating multiparous Holstein cows were used in a double 3 x 3 Latin square design (35-d periods) to study the effects of lasalocid (LAS) and monensin (MON) supplemented at 24 mg/ kg of dry matter on digestion, ruminal fermentation, blood metabolites, and milk production. Cows were blocked according to milk production and fed a red clover silage-based total mixed ration (17.8% crude protein) without supplementation or supplemented with LAS or MON. Daily dry matter intake, milk production, and milk fat and protein concentrations were similar among treatments and averaged 23.5 kg, 36.6 kg, 3.36%, and 3.38%, respectively. Rumen lipogenic:glucogenic volatile fatty acids and NH(3)-N concentration were lower, and apparent digestibility of dry matter, organic matter, crude protein, and gross energy were higher with than without ionophore supplementation. Compared with LAS, MON increased concentrations of plasma urea-N and milk urea-N, and excretion of urinary urea-N and total N. Monensin also decreased N retention and tended to reduce plasma concentration of nonessential AA in comparison with LAS. Both ionophores reduced daily fecal excretion of N by 13 g compared with the control, but MON increased daily losses of urinary N by 36 g compared with LAS. Results from this study suggest that postabsorptive metabolism of N might be altered by the type of ionophore fed.
Asunto(s)
Bovinos/metabolismo , Digestión/efectos de los fármacos , Ionóforos/farmacología , Lasalocido/farmacología , Monensina/farmacología , Rumen/metabolismo , Amoníaco/metabolismo , Animales , Análisis Químico de la Sangre , Nitrógeno de la Urea Sanguínea , Bovinos/sangre , Bovinos/fisiología , Estudios Cruzados , Suplementos Dietéticos , Ácidos Grasos Volátiles/metabolismo , Heces/química , Femenino , Fermentación/efectos de los fármacos , Ionóforos/administración & dosificación , Lactancia/efectos de los fármacos , Lactancia/fisiología , Lasalocido/administración & dosificación , Leche/química , Leche/metabolismo , Monensina/administración & dosificación , Nitrógeno/metabolismo , Nitrógeno/orinaRESUMEN
LPS-induced endotoxemia is associated with gut immune stimulation, mucosal inflammation, colonic paracellular permeability (CPP) alteration, and it promotes bacterial translocation (BT). Gut permeability increase linked to LPS promotes mucosal barrier dysfunction resulting to BT. However, the mechanisms involved in these alterations remain unknown. We aimed to evaluate the role of colonic mucosal mast cells and luminal serine protease activity (PA) in the alterations of CPP and BT induced by LPS. Rats receiving doxantrazole, a mast cell stabilizer, combined or not with LPS from Escherichia coli and CPP as well as BT were evaluated after each treatment. Mucosal mast cell activation was assessed by histological methods and by rat mast cell protease 2 level measurement in colonic content. Colonic luminal PA and mucosal inflammation (myeloperoxidase activity) were biochemically determined. In addition, the ability of luminal contents to act on CPP was evaluated in vitro in Ussing chambers. Peripheral administration of LPS promoted mast cell degranulation and increased CPP, BT, mucosal myeloperoxidase activity as well as rat mast cell protease 2 levels, and PA in colonic content. LPS-induced CPP increase and BT were prevented by doxantrazole. In vitro, exposure of the apical side of colonic tissues with supernatants from colonic contents of LPS-treated rats increased CPP. This effect was blocked by the serine protease inhibitor soybean trypsin inhibitor. Our data bring evidence of a key role of mucosal mast cells in LPS-induced increase of CPP and BT through the release of serine proteases into the colonic lumen.