monensin and Acidosis

Performance data on nearly 16,000 head of cattle that were used in trials to document effects of monensin on feedlot cattle were summarized. Cattle fed monensin-containing diets gained 1.6% faster, consumed 6.4% less feed and required 7.5% less feed/100 kg gain than cattle fed control diets. Monensin resulted in the greatest improvement in feed/gain at 2.9 Mcal metabolizable energy (ME)/kg diet dry matter (DM). Within the range of monensin concentrations used in the trials that were summarized (31.8 +/- 7.5 mg/kg DM), high monensin concentrations did not improve feed/gain over that obtained with lower concentrations. Carcass characteristics were not significantly influenced by monensin. Responses of cattle to monensin and implants were additive. Energy metabolism data suggested that monensin improved digestibility of DM, reduced fasting heat production and increased dietary net energy maintenance (NEm) values more than it increased net energy gain (NEg) values. Data showing the response of cattle to monensin when fed various dietary protein concentrations or sources of supplemental N suggested that monensin had a protein sparing effect. Monensin has also been shown to reduce lactic acid production, aid in the control of coccidia and bloat and to be toxic to face and horn fly larva in feces of monensin-fed cattle. In pasture trials, monensin improved daily gains. When fed to beef cows, monensin reduced amounts of feed required to maintain cow weight.

Topics: Acidosis; Animals; Body Weight; Cattle; Cattle Diseases; Coccidiosis; Dietary Proteins; Drug Implants; Energy Metabolism; Female; Food Additives; Furans; Lactates; Male; Models, Biological; Monensin; Nitrogen; Stomach Diseases

Monensin and functional oils (FO) were supplemented to a high-concentrate diet abruptly fed to 12 ruminally cannulated Zebu steers to study their effects on rumen fermentation, blood metabolites, and , , and relative population. A randomized complete block design with repeated measures over time within 2 experimental periods of 21 d each was used. Treatments were a control (CTR; with no additives), FO (included at 400 mg/kg), and monensin included at 30 mg/kg (M30) or 40 mg/kg (M40). All steers were fed the same high-concentrate basal diet, which consisted of 92.25% concentrate. The first 60 h after transition showed a treatment and hour interaction for ruminal propionate proportion ( = 0.028), and no change in acetate molar proportion ( = 0.633), rumen pH ( = 0.370), and time the rumen pH remained below 5.6 ( = 0.242) were observed. The acetate:propionate ratio decreased ( = 0.020) when monensin was fed in both concentrations (2.30 for the M30 treatment and 2.32 for the M40 treatment) compared with when the CTR was fed (2.85), without being different when the FO (2.71) treatment was fed. Only the M30 treatment did not show pH below 5.2 (P=0.047) over the 60 h after the abrupt transition. Within the entire period, DMI ( = 0.008) and mean ruminal pH ( = 0.040) as well as molar proportions of propionate ( = 0.034) and valerate ( = 0.031) had significant interactions between treatment and day. Total VFA concentration was greater ( = 0.017) for the M30 (117.36 m) and CTR treatments (115.77 m) compared with the M40 treatment (105.02 m), without being different for the FO treatment (111.55 m). Treatments did not change feed behavior parameters. Blood HCO ( = 0.006) and total carbon dioxide ( = 0.003) were greater for the M30 (27.8 and 29.3 mmol/L, respectively) and FO treatments (28.3 and 29.7 mmol/L, respectively) compared with the CTR treatment (25.7 and 26.9 mmol/L, respectively). ( < 0.0001) and ( < 0.0001) decreased their population throughout days, whereas ( = 0.026) increased its population. Independent of ciliated protozoa genera, the greatest ( < 0.0001) protozoa counts were observed for the CTR treatment (52.7 × 10/mL), intermediate for the FO treatment (35.3 x10/mL), and least for steers fed monensin in both concentrations (15 × 10/mL for the M30 treatment and 14 × 10/mL for the M40 treatment). Feed additives had different effects to reduce the subacute acidosis. The use of the FO and M40 treatments did not change most of the rumen fermentation varia

Topics: Acidosis; Anacardium; Animal Feed; Animals; Castor Oil; Cattle; Diet; Dietary Supplements; Eating; Feeding Behavior; Fermentation; Male; Monensin; Nuts; Rumen

Three trials were conducted to evaluate the efficacy of laidlomycin propionate (LP) to reduce the incidence and severity of ruminal acidosis in cattle fed high-grain finishing diets. In each trial, LP was fed at 0, 6, or 12 mg/kg of diet DM. In two acidosis-challenge trials, ruminally fistulated steers were fed (DM basis) a 50% concentrate diet and then fed a 95% concentrate diet at a specific intake (2.75% BW) or steers were dosed intraruminally with a 100% concentrate diet. Laidlomycin propionate did not alter ruminal pH or total acid concentrations, but in Trial 1 the 6 mg/kg level altered (P < .10) the molar proportions of the acids, increasing total ruminal VFA and decreasing ruminal lactate. In Trial 3, a finishing trial, LP reduced (P < .10) intake day-to-day variation of individually fed steers during a 13-d adaptation period from a 65 to a 100% concentrate diet, suggesting reduced incidence of subacute acidosis. Feed intake was lower (P < .05) during the first 13 d of the trial due to LP but was not affected over the entire trial. Laidlomycin propionate improved feed efficiency (gain/feed) when calculated on a live weight basis (linear, P = .05) or carcass weight basis (linear, P = .20). Laidlomycin propionate does not prevent ruminal acidosis, but it may reduce the severity of ruminal acidosis during adaptation to a 100% concentrate diet.

Topics: Acidosis; Animal Feed; Animals; Body Composition; Body Weight; Cattle; Cattle Diseases; Diet; Hydrogen-Ion Concentration; Ionophores; Male; Monensin; Rumen; Severity of Illness Index

Low reticuloruminal pH (rpH), often observed in subacute ruminal acidosis (SARA), may negatively affect rumen health and animal performance. To investigate the variability of rpH and the prevalence of SARA on commercial farms, we conducted an observational study on 110 early-lactation Holstein cows of different parities from 12 farms selected to cover a broad range of farm management strategies. The rpH of each cow was continuously monitored for 50 d using wireless boluses. To study the effects of animal and farm management characteristics on rpH, we used a multivariable mixed model analysis with the animal and farm as random effects. Automatic milking system and presence of corn silage in the ration were associated with a decrease in rpH of 0.37 and 0.20 pH units, respectively, whereas monensin supplementation was associated with an increase of 0.27 pH units. The rpH increased by 0.15 pH units during the first 60 d in milk. We defined a SARA-positive day as rpH below 5.8 (SARA5.8) or 6.0 (SARA6.0) for at least 300 min for 1 d. Using those definitions, during our study, a total of 38 (35%) and 65 (59%) cows experienced at least one episode of SARA5.8 and SARA6.0, respectively. The proportion of cows with at least one SARA-positive day varied among farms from 0 to 100%. Automatic milking system was associated with an increased risk of SARA5.8 (odds ratio: 10) and SARA6.0 (odds ratio: 11). The use of corn silage was associated with an increased risk of SARA5.8 (odds ratio: 21), whereas the use of monensin was associated with a decreased risk of SARA5.8 (odds ratio: 0.02). Our study shows that rpH is quite variable among farms, but also among animals on the same farm. We also show that multiple animal and farm characteristics are associated with rpH variability and the risk of SARA under commercial conditions.

Topics: Acidosis; Animals; Cattle; Cattle Diseases; Diet; Farms; Female; Hydrogen-Ion Concentration; Lactation; Monensin; Rumen

In recent years, researchers have become increasingly interested in developing natural feed additives that can stabilize ruminal pH and thus prevent or eliminate the risk of severe subacute rumen acidosis. Herein, 3 experiments were conducted using a semi-automated in vitro gas production technique. In the experiment (Exp.) 1, the efficacy of 9 plant extracts (1.5 mg/ml), compared to monensin (MON; 12 μg/ml), to counteract ruminal acidosis stimulated by adding glucose (0.1 g/ml) as a fermentable carbohydrate without buffer was assessed for 6 h. In Exp. 2, cinnamon extract (CIN) and MON were evaluated to combat glucose-induced acidosis with buffer use for 24 h. In Exp. 3, the effect of CIN and MON on preventing acidosis when corn or barley grains were used as substrate was examined.. In Exp. 1, cinnamon, grape seeds, orange, pomegranate peels, propolis, and guava extracts significantly increased (P < 0.05) pH compared to control (CON). Both CIN and MON significantly increased the pH (P < 0.001) but reduced cumulated gas production (P < 0.01) compared to the other treatments. In Exp. 2, the addition of CIN extract increased (P < 0.01) pH value compared to CON at the first 6 h of incubation. However, no significant differences in pH values between CIN and CON at 24 h of incubation were observed. The addition of CIN extract and MON decreased (P < 0.001) lactic acid concentration and TVFA compared to CON at 24 h. The CIN significantly (P < 0.01) increased acetate: propionate ratio while MON reduced it. In Exp. 3, both CIN and MON significantly increased (P < 0.05) ruminal pH at 6 and 24 h and reduced lactic acid concentration at 24 h compared to CON with corn as substrate. However, CIN had no effect on pH with barley substrate at all incubation times.. It can be concluded that CIN can be used effectively as an alternative antibiotic to MON to control ruminal acidosis when corn is used as a basal diet.

Topics: Acidosis; Animal Feed; Animals; Anti-Bacterial Agents; Carbohydrates; Cinnamomum zeylanicum; Diet; Digestion; Fermentation; Glucose; Lactic Acid; Monensin; Plant Extracts; Propionates; Propolis; Rumen

Many feedlot finishing diets include wheat when the relative wheat prices are low. This study was conducted to examine the responses in ruminal pH and fermentation as well as site and extent of digestion from substituting soft or hard wheat for barley grain and to determine whether an elevated monensin concentration might decrease indicators of ruminal acidosis in feedlot heifers. Five ruminally cannulated beef heifers were used in a 5 × 5 Latin square with 2 × 2 + 1 factorial arrangement. Treatments included barley (10% barley silage, 86% barley, 4% supplement, with 28 mg monensin/kg DM) and diets where barley was substituted by either soft or hard wheat with either 28 or 44 mg monensin/kg diet DM. Intake of DM was not affected by grain source, whereas increasing monensin with wheat diets reduced (P < 0.02) DMI. Mean ruminal pH was lower (P < 0.04) and durations of pH < 5.8 and pH < 5.5 greater (P < 0.03) for wheat than for barley diets. However, ruminal pH was not affected by wheat type or monensin level. Total VFA concentrations were greater (P < 0.03) for wheat than barley diets with no effect of wheat type. The molar proportion of propionate was greater (P < 0.04), whereas butyrate (P < 0.01) and ratio of acetate to propionate tended to be lower (P < 0.09), with the high as compared to low level of monensin. Replacing barley with wheat in finishing diets did not affect the duodenal flow or the digestibility of OM, likely as a result of greater (P < 0.01) NDF digestion from barley offsetting the increased (P < 0.03) supply of digested starch from wheat. Feeding soft vs. hard wheat delivered a greater (P < 0.03) duodenal supply of OM and nonammonia N with no differences in total tract nutrient digestion. The increased monensin concentration decreased the flow of OM (P < 0.01), total N (P < 0.05), and microbial protein (P < 0.05) to the small intestine due to decreased DMI. These results indicated that hard and soft wheat exhibited digestive characteristics similar to barley, but ruminal pH measurements indicate that compared with barley, wheat increased the risk of ruminal acidosis. Although an increased level of monensin had limited impact on ruminal indicators of acidosis, an increase in propionate would be expected to improve efficiency of feed use by heifers fed wheat-based finishing diets.

Topics: Acidosis; Animal Nutritional Physiological Phenomena; Animals; Cattle; Cattle Diseases; Diet; Dietary Supplements; Digestion; Duodenum; Edible Grain; Female; Fermentation; Hordeum; Monensin; Rumen; Silage; Triticum

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.

Topics: Acidosis; Animal Feed; Animals; Anti-Bacterial Agents; Diet; Dietary Carbohydrates; Drug Resistance; History, 16th Century; Hydrogen-Ion Concentration; Ionophores; Lasalocid; Male; Monensin; Pediococcus; Phylogeny; RNA, Ribosomal, 16S; Rumen; Sheep; Sheep Diseases

To determine the prevalence of subacute rumen acidosis (SARA) in beef cattle grazing lush pasture and the effect of monensin on reducing SARA and improving animal performance.. Commercial Angus and Murray Grey steers received a monensin slow-release capsule (n = 19) or remained untreated (n = 19). Cattle grazed an oats crop or tetraploid ryegrass pasture for a total of 91 days. Rumen fluid pH, volatile fatty acids (VFA) and lactic acid concentrations and body weight data were collected prior to treatment and again 28, 56 and 91 days after treatment. Changes in measures over time were analysed using mixed model repeated measures analysis. Differences in average daily gain between treatment groups were determined.. The prevalence of SARA was low during the study, with only one animal satisfying criteria for SARA at one time point. Cattle treated with monensin capsules were 11.9 kg heavier at the completion of the study compared with untreated controls (414.5 ± 3.88 kg vs 402.6 ± 4.03 kg, P = 0.04). Rumen VFA and L- and D-lactate levels did not differ between cattle treated with monensin and untreated cattle. However, the ratio of propionate to acetate plus two times butyrate was higher (P < 0.001) when cattle were treated with monensin.. Subacute rumen acidosis was not consistently detected under the conditions of the study. The higher body weight of cattle treated with monensin may have been due to improved energy utilisation of the pasture, indicated by increased propionate proportions in the rumen, rather than prevention of SARA.

Topics: Acidosis; Animal Feed; Animals; Cattle; Fermentation; Male; Monensin; Poaceae; Random Allocation; Rumen; Weight Gain

The effects of monensin premix supplementation on ruminal pH characteristics and forage degradability, and total tract diet digestibility during grain-induced subacute ruminal acidosis (SARA) in lactating dairy cows receiving a total mixed ration were investigated. Six multiparous, rumen-fistulated Holstein cows were used in a 2-treatment, 2-period (5 wk per period) crossover design. During wk 5 (d 29 to 35) of each period, SARA was induced using a grain challenge model, and ruminal pH was measured continuously using indwelling pH probes. Ruminal degradation of corn silage and alfalfa haylage was determined using the in situ (nylon bag) technique, and total tract diet digestibility was determined by total fecal collection during wk 5. Monensin supplementation did not affect dry matter intake, milk yield, and composition, and ruminal pH characteristics under these experimentally induced SARA conditions. Rates of ruminal forage fiber degradability were similar between control and monensin-treated cows; however, monensin supplementation increased total tract fiber digestion. This study indicates that monensin altered total tract nutrient digestion by increasing fiber digestion at postruminal sites.

Topics: Acidosis; Analysis of Variance; Animals; Cattle; Cattle Diseases; Cross-Over Studies; Dietary Fiber; Dietary Supplements; Digestion; Eating; Feces; Female; Hydrogen-Ion Concentration; Ionophores; Lactation; Medicago sativa; Milk; Monensin; Random Allocation; Rumen; Silage; Zea mays

Two commercial feedlot experiments and a metabolism study were conducted to evaluate the effects of monensin concentrations and bunk management strategies on performance, feed intake, and ruminal metabolism. In the feedlot experiments, 1,793 and 1,615 steers were used in Exp. 1 and 2, respectively, in 18 pens for each experiment (six pens/treatment). Three treatments were evaluated: 1) ad libitum bunk management with 28.6 mg/kg monensin and clean bunk management strategies with either 2) 28.6 or 3) 36.3 mg/kg monensin. In both experiments, 54 to 59% of the clean bunk pens were clean at targeted clean time, or 2200, compared with 24 to 28% of the ad libitum pens. However, only 13% of the pens were clean by 2000 in Exp. 1 (summer), whereas 44% of the pens in Exp. 2 (winter) were clean by 2000. In Exp. 1, bunk management and monensin concentration did not affect carcass-adjusted performance. In Exp. 2, steers fed ad libitum had greater DMI (P < 0.01) and carcass-adjusted ADG (P < 0.01) but feed efficiency (P > 0.13) similar to that of clean bunk-fed steers. Monensin concentration had no effect on carcass-adjusted performance (P > 0.20) in either experiment. A metabolism experiment was conducted with eight fistulated steers in a replicated 4 x 4 Latin square acidosis challenge experiment. An acidosis challenge was imposed by feeding 125% of the previous day's DMI, 4 h later than normal. Treatments consisted of monensin concentrations (mg/kg) of 0, 36.7, 48.9, or 36.7 until challenged and switched to 48.9 on the challenge day and 4 d following. Each replicate of the Latin square was managed with separate bunk management strategies (clean bunk or ad libitum). Feeding any concentration of monensin increased number of meals and decreased DMI rate (%/h) (P < 0.12) for the 4 d following the acidosis challenge. Meal size, pH change, and pH variance were lower (P < 0.10) for steers fed monensin with clean bunk management. However, no monensin effect was observed for steers fed ad libitum. Bunk management strategy has the potential to decrease DMI and ADG when steers managed on a clean bunk program are restricted relative to traditional, ad libitum bunk programs. Monensin helps control intake patterns for individuals, but increasing concentration above currently approved levels in this study seemed to have little effect.

Topics: Acidosis; Animal Feed; Animal Husbandry; Animals; Cattle; Digestion; Dose-Response Relationship, Drug; Eating; Hydrogen-Ion Concentration; Ionophores; Male; Monensin; Random Allocation; Rumen; Seasons; Weight Gain

The effects of a monensin premix on milk fatty acid content during grain-induced subacute ruminal acidosis (SARA) in Holstein cows receiving a total mixed ration was investigated. Six multiparous, rumen-fistulated Holstein cows were used in a two-treatment, two-period crossover design with 6-wk periods. Experimental treatments were either a monensin premix or a placebo premix. At the beginning of wk 4, SARA was induced in experimental cows for a 10-d period using a grain challenge model. The administration of a monensin premix elevated milk fat proportion of total short-chain saturated fatty acids (sum of C4 to C15). Milk fat proportions of conjugated linoleic acid isomers were unaffected. Linolenic acid (C18:3n3) proportion in milk fat of monensin-treated cows were lower when compared with placebo-treated cows during the SARA period. Results from this study indicate that dietary supplementation with monensin during SARA had little effect on milk fatty acid content.

Topics: Acidosis; alpha-Linolenic Acid; Analysis of Variance; Animals; Cattle; Cattle Diseases; Cross-Over Studies; Fatty Acids; Female; Ionophores; Linoleic Acid; Lipids; Milk; Monensin; Placebos; Rumen

The effects of monensin, administered either as a controlled release capsule (CRC) or a premix, on attenuating grain-induced subacute ruminal acidosis (SARA) and on ruminal fermentation characteristics in Holstein cows receiving a total mixed ration were investigated in two experiments. In both experiments, six multiparous, rumen-fistulated Holstein cows were used in a two-treatment, two-period crossover design with 6-wk periods. In Experiment 1, treatments were either a monensin CRC or a placebo CRC. In Experiment 2, treatments were either a monensin premix or a placebo premix. In both experiments, at the beginning of wk 4 SARA was induced in experimental cows for a 10-d period with a grain challenge model, and ruminal pH was measured continuously using indwelling pH probes. The administration of monensin either as a CRC or a premix had no effect on ruminal pH characteristics. Neither monensin CRC nor premix had an effect on ruminal volatile fatty acid concentrations, but reduced the acetate:propionate ratio. Monensin premix-treated cows were observed to have increased milk yield, largely as a result of a higher dry matter intake in monensin-treated cows compared to control cows. Milk fat content and yield were lower in monensin-treated cows compared to placebo-treated cows during SARA. In conclusion, there is no evidence that monensin was efficacious in raising ruminal pH during SARA under the conditions employed in this study.

Topics: Acidosis; Animals; Cattle; Cattle Diseases; Delayed-Action Preparations; Diet; Eating; Fatty Acids, Volatile; Female; Fermentation; Hydrogen-Ion Concentration; Lactose; Lipids; Milk; Milk Proteins; Monensin; Rumen; Stomach Diseases

This study investigates the effects of intracellular (pH(i)) and extracellular pH (pH(e)) on the efflux of Rb(+) and Li(+) in isolated rat hearts. (87)Rb and (7)Li NMR were used to measure Rb(+) and Li(+) content, respectively, of hearts, and (31)P NMR was used to monitor pH(i), pH(e), and phosphate levels. After 30-min equilibration with Rb(+) or Li(+), effluxes were initiated by switching perfusion to a Rb(+)- or Li(+)-free, high-K(+) (20.7 mM) Krebs-Henseleit buffer with 15 microM bumetanide. Monensin (2 microM) increased pH(i) from 7.10 +/- 0.05 to 7.32 +/- 0.07 and resulted in activation of Rb(+) efflux; the first-order rate constant (k x 10(3), in min(-1)) increased from 42 +/- 2 to 116 +/- 16. Glibenclamide (4 microM) did not inhibit monensin-activated Rb(+) efflux (k = 110 +/- 17), whereas quinine (0.2 mM) slightly inhibited it by 19 +/- 9%. Infusion of 15 mM NH(4)Cl during Rb(+) washout increased k for Rb(+) efflux by 93% (81 +/- 8), which was glibenclamide and quinine insensitive, and caused a transient increase in pH(i) to 7.25 +/- 0.08. Intracellular Li(+) inhibited NH(4)Cl-stimulated Rb(+) efflux by 55%. Monensin and NH(4)Cl stimulated Li(+) efflux by 40%, increasing k from 29 +/- 3 to 43 +/- 7 and 41 +/- 3, respectively. The stimulation was not sensitive to 10 microM dimethylamiloride. Intracellular acidosis that resulted from the washout of NH(4)Cl (pH 6.86 +/- 0.2) slightly inhibited Rb(+) efflux (k = 36 +/- 5), whereas NH(4)Cl itself in the absence of pH(i) changes did not markedly affect Rb(+) efflux. A moderate increase in pH(i) (7.17 +/- 0.06) produced by washout of 15 mM 2, 2-dimethylpropionate (DMP)-Tris from hearts preequilibrated with DMP did not markedly affect Rb(+) efflux. Neither global alkalosis (pH(i) 7.4, pH(e) 7.55) nor acidosis (pH(i) approximately pH(e) 6.8) produced by 3 mM Tris base or 5 mM MES, respectively, affected Rb(+) efflux. We suggest that intracellular alkalosis stimulates Rb(+) (K(+)) and Li(+) effluxes by activating a nonselective sarcolemmal K(+) (Li(+))/cation exchanger or a K(+) (Li(+))-anion symporter.

Topics: Acidosis; Alkalosis; Ammonium Chloride; Animals; Hydrogen-Ion Concentration; In Vitro Techniques; Lithium; Magnetic Resonance Spectroscopy; Male; Monensin; Myocardium; Phosphorus; Potassium; Rats; Rats, Sprague-Dawley; Rubidium Radioisotopes

The killing of isolated hepatocytes by N-acetyl-p-benzoquinone imine (NAPQI), the major metabolite of the oxidation of the hepatotoxin acetaminophen, has been studied previously as a model of liver cell injury by the parent compound. Such studies assume that the toxicity of acetaminophen is mediated by NAPQI and that treatment with exogenous NAPQI reproduces the action of the endogenously produced product. The present study tested these assumptions by comparing under identical conditions the toxicity of acetaminophen and NAPQI. The killing of hepatocytes by acetaminophen was mediated by oxidative injury. Thus, it depended on a cellular source of ferric iron; was potentiated by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase; and was sensitive to antioxidants. By contrast, the cytotoxicity of NAPQI was not prevented by chelation of ferric iron; was unaffected by BCNU; and was insensitive to antioxidants. Thus, the killing of cultured hepatocytes by NAPQI occurs by a mechanism different from that of acetaminophen. The killing by NAPQI was preceded by a collapse of the mitochondrial membrane potential and a depletion of ATP. Monensin potentiated the cell killing, and extracellular acidosis prevented it. These manipulations are characteristic of the toxicity of mitochondrial poisons, and are without effect on the depletion of ATP and the loss of mitochondrial energization. Thus, mitochondrial de-energization by a mechanism unrelated to oxidative stress is a likely basis of the cell killing by NAPQI. It is concluded that treatment of cultured hepatocytes with NAPQI does not model the cytotoxicity of acetaminophen in these cells.

Topics: Acetaminophen; Acidosis; Adenosine Triphosphate; Animals; Benzoflavones; Benzoquinones; beta-Naphthoflavone; Carmustine; Cell Survival; Cells, Cultured; Deferoxamine; Glutathione; Glutathione Reductase; Imines; In Vitro Techniques; Liver; Models, Biological; Monensin; Oxidation-Reduction; Phenylenediamines; Rats

Interactions among grain type (grain sorghum, corn or wheat), roughage level and monensin level were studied in four feedlot trials using pen-fed crossbred yearling cattle. In Trial 1, cattle fed high-moisture corn (HMC) were more efficient (.1537 vs .1406 for gain/feed; P less than .01) than cattle fed dry-rolled grain sorghum (DRGS). As level (0, 3, 6, 9%) of dietary roughage was increased, feed efficiency (gain/feed) decreased (.1566, .1461, .1479, .1382; linear, P less than .01). In Trial 2, a grain type (DRGS; dry-rolled corn, DRC; dry-rolled wheat, DRW) x roughage level interaction was observed for daily gain and feed efficiency. Feed efficiency (gain/feed) was decreased when roughage was added to diets containing DRC (.1608 vs .1750) or DRGS (.1674 vs .1465), but not to the diet containing DRW (.1664 vs .1607). In trial 3, a grain type x roughage level x monensin level interaction (P less than .08) was observed for feed efficiency. The addition of 27.5 mg of monensin per kilogram of the 0% roughage-DRC diet tended to improve feed efficiency (.1633 vs .1531), but the addition of monensin to the 7.5% roughage-DRC diet tended to depress feed efficiency (.1476 vs .1575). The addition of either roughage (.1493 vs .1420) or monensin (.1500 vs .1413) to the DRW diet improved feed efficiency. In Trial 4, cattle fed a combination of 75% DRW and 25% DRC were more efficient (.1618 vs .1591; P less than .06) than cattle fed DRC. As level of roughage (0, 3.75, 7.5%) increased, feed efficiency decreased linearly (.1645, .1599, .1569; P less than .0001). Monensin had no effect on feed efficiency. The value of feeding roughage and monensin was variable both across grain types and within similar grain types.

Topics: Acidosis; Animal Feed; Animals; Cattle; Cattle Diseases; Dietary Fiber; Digestion; Eating; Edible Grain; Liver Abscess; Male; Monensin; Starch; Weight Gain

The relationships between extracellular pH (pHo), intracellular pH (pHi), and loss of cell viability were evaluated in cultured rat hepatocytes after ATP depletion by metabolic inhibition with KCN and iodoacetate (chemical hypoxia). pHi was measured in single cells by ratio imaging of 2',7'-biscarboxy-ethyl-5,6-carboxyfluorescein (BCECF) fluorescence using multiparameter digitized video microscopy. During chemical hypoxia at pHo of 7.4, pHi decreased from 7.36 to 6.33 within 10 min. pHi remained at 6.1-6.5 for 30-40 min (plateau phase). Thereafter, pHi began to rise and cell death ensued within minutes, as evidenced by nuclear staining with propidium iodide and coincident leakage of BCECF from the cytoplasm. An acidic pHo produced a slightly greater drop in pHi, prolonged the plateau phase of intracellular acidosis, and delayed the onset of cell death. Inhibition of Na+/H+ exchange also prolonged the plateau phase and delayed cell death. In contrast, monensin or substitution of gluconate for Cl- in buffer containing HCO3- abolished the pH gradient across the plasma membrane and shortened cell survival. The results indicate that intracellular acidosis after ATP depletion delays the onset of cell death, whereas reduction of the degree of acidosis accelerates cell killing. We conclude that intracellular acidosis protects against hepatocellular death from ATP depletion, a phenomenon that may represent a protective adaptation against hypoxic and ischemic stress.

Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Acidosis; Amiloride; Animals; Bicarbonates; Carrier Proteins; Cell Survival; Cells, Cultured; Chlorides; Fluoresceins; Gluconates; Hydrogen-Ion Concentration; Liver; Male; Monensin; Oxygen; Rats; Rats, Inbred Strains; Sodium-Hydrogen Exchangers

Holstein cows, second lactation or later, were gradually introduced to monensin-containing concentrate 1 wk prepartum and fed complete diets containing 15 and 30 g monensin/ton of DM for 3 wk postpartum. The addition of 30 g monensin/ton of feed decreased the incidence of subclinical ketosis from 6 out of 12 to 1 out of 12. The concentration of beta-hydroxybutyrate in blood from cows in the high monensin group was decreased during the 3-wk postpartum experimental period. Acetate: propionate ratios decreased from 2.32 in the control group to 1.44 in the high monensin group. Feed intake in the low monensin group was less than in the control group, but there were no significant differences in body weight changes or milk production. Monensin, when added to the diet, lowered milk fat in one of the monensin fed groups (low) but not in the other. Milk protein and lactose concentrations were not changed by the addition of monensin to the diet. No other adverse treatment effects were observed. Two cows from each group were culled for causes unrelated to treatment; the remainder completed the normal 305-d lactation and were rebred without problems.

Topics: Acidosis; Animals; Blood Glucose; Cattle; Fatty Acids, Volatile; Female; Ketone Bodies; Ketosis; Lactation; Lipids; Monensin; Pregnancy; Rumen

Two finishing trials were conducted to measure the response of cattle adjusting to high-concentrate diets to dietary monensin level. In trial 1, 54 individually fed Hereford-Angus steers (312 kg), previously fed a two-thirds corn silage: one-third corncob-based diet, were allotted in a 2 X 3 factorial arrangement of treatment with tylosin (0, 11 mg/kg) and monesin (0, 11, 33 mg/kg) fed during a 28-d, grain-adaptation period (fed 75% concentrate for 6 d and then fed 95% concentrate). After 28 d, all steers were continued on their respective levels of tylosin and 33 mg/kg monensin for the remaining 119 d. Daily intake patterns indicated digestive upset in all treatments during adjustment to the 95%-concentrate diet. Blood samples taken during the first 28 d revealed no differences in acid-base status in response to monensin level; however, all steers exhibited reduced (P less than .01) pH and HCO3 and increased (P less than .01) lactate after 4 d on a 75%-concentrate diet. In the initial 28 d, intake decreased (linear P less than .05) as the level of monensin increased. In the total finishing period, however, increasing the level of monensin fed during grain adaptation decreased (linear P less than .05) intake and tended to decrease (linear P = .20) gain with no effect on feed efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acidosis; Adaptation, Physiological; Animal Feed; Animals; Body Weight; Cattle; Edible Grain; Leucomycins; Male; Monensin

A steer metabolism study was conducted to measure changes in ruminal and blood components in response to monensin level following an abrupt switch from forage to a concentrate diet. Six ruminal-cannulated crossbred steers (373 kg) were fed either 0, 150 or 300 mg monensin per head daily in a replicated 3 X 3 Latin-square design. In all treatments, ruminal pH declined to a low of 5.4 to 5.6 12 h post-feeding, suggesting steers experienced subacute acidosis. Also in the first 12 h post-feeding, all treatments exhibited nearly a twofold increase in total ruminal volatile fatty acid (VFA) concentrations, while peak ruminal lactate concentrations ranged from .86 to 1.50 mM. During the entire 48-h period, there were no significant treatment differences in blood pH, HCO3- or ruminal lactate, although there was a trend of higher ruminal and blood lactate associated with increased level of monensin supplementation. Feeding higher levels of monensin resulted in higher pH and propionate with lower acetate and butyrate concentrations. Increasing the level of monensin fed resulted in reduced (P less than .01) total ruminal VFA concentrations. Ruminal pH was more highly correlated to total ruminal VFA concentrations (r = -.69, P less than .01) than lactate concentrations (r = -.14, P less than .10). Results from this study indicate the significance of total ruminal organic acid concentration rather than ruminal lactate concentration during subacute acidosis. Monensin maintained a higher ruminal pH by reducing concentrations of VFA.

Topics: Acidosis; Animals; Cattle; Cattle Diseases; Male; Monensin

Salinomycin, a new ionophore antibiotic, was tested and compared with lasalocid and monensin for preventing experimentally induced lactic acidosis. Five rumen-fistulated adult cattle were used in a 5 X 5 Latin square design, and the treatments were as follows: no treatment (control), 0.11 mg of salinomycin/kg of body weight (S1), 0.22 mg of salinomycin/kg (S2), 0.66 of lasalocid/kg, and 0.66 mg of monensin/kg. Acidosis was induced by intraruminal administration of a ground corn-corn starch mixture (50:50, 12.5 g/kg) once a day for up to 4 days. Antibiotics were administered along with grain-starch mixture. Rumen and blood samples were obtained before and at 6, 12, and 24 hours after each carbohydrate-antibiotic dosing to monitor acid-base status. Control and S1-treated cattle became ruminally acidotic within 54 hours, whereas cattle treated with S2, lasalocid, and monensin resisted acidosis for up to 78 hours after dosing. Cattle treated with S2, lasalocid, or monensin had higher rumen pH and lower L(+)- and D(-)-lactate concentrations than did control or S1-treated cattle. Rumen pH decrease to below 5.0 in S2-, lasalocid-, and monensin-treated cattle was not due to lactic acid, but to increased production of volatile fatty acids. Rumen propionate proportion increased initially in antibiotic-treated cattle, but after 48 hours, butyrate proportion increased significantly. Despite low rumen pH and high lactate concentration, lacticacidemia was not evident, and the systemic acid-base disturbance was mild in control cattle.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acidosis; Animal Feed; Animals; Cattle; Cattle Diseases; Food Additives; Hydrogen-Ion Concentration; Lactates; Lasalocid; Monensin; Pyrans; Rumen

Experiments were carried out with sheep and cows on the basis of a limited feed ration--the giving of concentrates was discontinued, and the ration of alfalfa hay was replaced with meadow hay and a monensine supplement (at the rate of 20-25 mg for sheep and 250 mg for cows, daily), and nicotinic acid (at 0.8 g and 6.0 g, respectively). Observations revealed that in the course of 6-7 weeks in succession the drop of blood sugar was reduced, and monensine led to a rise of the alkali reserves of the blood by 27 to 41 per cent. Cows with ketonuria (from ++ up to + positive results with the nitroprusside tests) and hydroglycaemia (blood sugar up to 30 mg) were treated with monensine at the rate of 125 mg, in the morning and in the evening or with nicotinic acid at 3 g and the same frequency for 6-7 consecutive days. The symptoms receded to a greater extent (12.1 to 60 per cent) as compared to the process of self-healing for the same time period. In this respect the effect of monensine was better manifested. It was demonstrated that the prophylactic use of these drugs inhibited to a minimum the manifestation of hypoglycaemia and ketonuria.

Topics: Acidosis; Animals; Cattle; Cattle Diseases; Drug Evaluation; Female; Furans; Ketosis; Monensin; Niacin; Sheep; Sheep Diseases; Time Factors

Lasalocid, monensin or thiopeptin was administered intraruminally each at .33, .65 or 1.3 mg/kg body weight and evaluated for its effectiveness in preventing experimentally induced lactic acidosis in cattle. Four rumen-fistulated cattle were used for each dosage level and the design was a 4 x 4 Latin square with each animal receiving lasalocid, monensin, thiopeptin or no antibiotic. Acidosis was induced by intraruminal administration of glucose (12.5 g/kg body weight). Control cattle exhibited the typical drop in rumen pH and concurrent increases in L(+) and D(-) lactate concentrations commonly observed in cases of lactic acidosis. Alkali reserves were depleted in the control cattle as evidenced by a decrease in blood bicarbonate and a negative shift in base excess. In all three trials, cattle given lasalocid had higher rumen pH and lower lactate concentrations than did control cattle or cattle given monensin or thiopeptin. Cattle given monensin had a significantly higher rumen pH and a lower lactate concentration than the controls only at the .65 and 1.3 mg/kg body weight dosages, whereas thiopeptin was effective only at the 1.3-mg dosage. Concentrations of total VFA in rumen fluid decreased in the controls but remained unchanged in cattle given antibiotics. A significant reduction in the molar proportion of acetate and an increase in the molar proportion of propionate were observed in the rumen fluid of the cattle given antibiotics. Colony counts of Streptococcus bovis and Lactobacillus were significantly reduced in rumen fluid of cattle given 1.3 mg antibiotic/kg body weight. Counts of lactate-utilizing bacteria increased in both control cattle and cattle given antibiotics. Cattle given antibiotics showed no evidence of lacticacidemia, hemoconcentration or change in acid-base balance.

Topics: Acidosis; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Cattle; Fatty Acids, Volatile; Furans; Hydrogen-Ion Concentration; Lactates; Lasalocid; Monensin; Peptides; Rumen

Intraruminal administration of lasalocid or monensin (1.3 mg/kg body weight) effectively prevented in glucose- or corn-induced lactic acidosis in cattle. Administering the antibiotics for 7 days before experimentally inducing acidosis with corn (27.5 g/kg body weight), effectively prevented acidosis, while 2 days' were sufficient to prevent glucose-induced acidosis (12.5 g/kg body weight). The different responses observed in the two trials probably stemmed from the difference in amounts of carbohydrate used to induce acidosis. Antibiotic-treated cattle had higher rumen pH values and lower L(+) and D(-) lactate concentrations that control cattle that received no antibiotics. Ruminal VFA in control cattle decreased, while total VFA and the molar proportion of propionate increased in antibiotic-treated cattle after grain engorgement. Control cattle exhibited classic signs of acidosis, such as lowered blood pH; increased blood lactate, particularly D(-) isomer; hemoconcentration, and depleted alkali reserve with a pronounced based deficit. Antibiotic-treated cattle exhibited no signs of systemic acidosis.

Topics: Acidosis; Animals; Cattle; Cattle Diseases; Furans; Hydrogen-Ion Concentration; Lactates; Lasalocid; Male; Monensin; Rumen

Topics: Acidosis; Animals; Cattle; Cattle Diseases; Female; Furans; Ketosis; Monensin; Nitrates