Monensin Toxicosis Research Articles

Monensin toxicosis in a dog with initial apparent recovery followed by severe relapse

AbstractThis case report describes successful intensive care management of a toxic myopathy in a 7‐month‐old, female, entire springer spaniel secondary to presumed monensin intoxication. The dog was seen chewing a monensin capsule, and was subsequently presented to the local veterinary practice with generalised weakness, ataxia, hypersalivation and pyrexia. Intravenous lipid emulsion‐activated charcoal and intensive fluid therapy were administered. Bloodwork identified a marked increase in serum creatine kinase activity (226,554 iu/L; reference range: 0–400 iu/L). The patient was discharged the following day after initial hospitalisation, with a complete resolution of clinical signs. Five days after exposure, a rapid deterioration required veterinary assessment at the referral hospital. The patient recovered and was discharged after 9 days of hospitalisation. This case report describes recurrence of clinical signs of monensin toxicosis after initial improvement. However, with aggressive emergency care, symptomatic therapy and intense monitoring, a positive outcome was achieved.

Gross Pathology, Biochemistry and Histopathology of Selected Organs of Camels Suffering from Suspected Monensin Toxicosis in Australia

The rumen modifier monensin is widely used in Australia cattle production systems. In addition to its anti-coccidial action monensin improves energy efficiency and nitrogen metabolism in rumen bacteria, and reduces the incidence of metabolic disorders such as acidosis and bloat. While monensin is considered safe for cattle, swine and poultry, it is extremely toxic to horses and incidents of toxicity have also been reported in camels. In this study, we are reporting for the first time monensin toxicosis in a camel herd in South-West Queensland, Australia (~267 km west of Brisbane). The camels were fed a cattle breeder supplements containing 250 mg/kg monensin, formulated to ensure effective concentrations if the supplement is consumed by breeder cattle at levels of 200-500 g/head/d. Blood samples were collected from 13 camels with clinical signs of monensin toxicosis and 12 healthy camels that had no exposure to monensin. Post-mortem examinations were carried out on two camels immediately after death, these animals had marked ascites. Monensin toxicoses resulted in marked decreases in albumin and increases in ALP, LDH and CPK when compared to physiologically normal healthy camels. Other parameters in the blood profile remain within normal limits. Minor to no histopathological changes were observed in the two necropsied camels however death due to rapidly developing congestive heart failure is suspected. Skeletal muscle was not examined histologically. However, the biochemical changes could be consistent with muscle necrosis.

Diagnostic value of tissue monensin concentrations in horses following toxicosis

Two separate incidents of monensin exposure in horses resulting in toxicosis provided insight into the diagnostic value and interpretive criteria of various biological samples. In case 1, 25 horses broke into a shed and ingested feed that was supplemented with 800 g/ton (880 µg/g) of monensin. Within 48 hr, 1 horse had died, 2 developed cardiac arrhythmias, lethargy, and recumbency, and another was euthanized due to severe deterioration. Minimal histologic lesions were noted in the horse that died peracutely, while another showed characteristic lesions of acute cardiomyocyte degeneration and necrosis. Stomach content, heart, liver, urine, and serum revealed various detectable concentrations of monensin in clinically affected and unaffected horses with known exposure. In case 2, a pastured horse had access to a mineral mix containing 1,600 g/ton (1,760 µg/g) of monensin. Within 48 hr, the horse became symptomatic and was euthanized because of severe respiratory distress. Histologic cardiac lesions were minimal but detectable amounts of monensin were found in blood, heart, liver, and stomach contents. In both cases, monensin toxicosis was confirmed with toxicological analysis. These cases demonstrate an overall lack of correlation of monensin concentrations in various biological samples with clinical outcome. However, serum, urine, blood, liver, heart, and stomach content can be tested to confirm exposure. More importantly, the consistently higher concentrations found in heart tissue suggest this is the most useful diagnostic specimen for postmortem confirmation of toxicosis in horses especially in cases in which associated feed cannot be tested for monensin or in cases with no histologic lesions.

Correlation of Serum Cardiac Troponin I and Myocardial Damage in Cattle with Monensin Toxicosis

Cardiac troponin I (cTnI) is used as a biomarker of myocardial injury in people and small animals. Little is known about the diagnostic use of cTnI in cattle. Serum cTnI correlates to myocardial function and histopathologic lesions in cattle with monensin-induced myocardial injury. Ten healthy cows. Experimental study. Animals received 1 dose of monensin PO; 30 mg/kg (n = 1) or 40 mg/kg (n = 1) (Group A) or 50 mg/kg monensin (n = 8) (Group B) of body weight. Repeated measurements were performed of serum cTnI, biochemistry, and ECG and echocardiography until study termination at 80 (Group A) and 144 hours (Group B) after dosing. Semiquantitative histopathologic examinations of the heart were performed in each cow. A scoring system with regard to the magnitude of myocardial injury was established and a total heart score was compared with maximum cTnI concentration measured after monensin administration. Five hearts from healthy cows served as controls. Increased cTnI (>0.07 ng/mL) was found in 9/10 cows. cTnI was significantly associated with left ventricular shortening fraction (r(2)= 0.51; P= .02) and myocardial histopathologic lesion score (r(2)= 0.49; P= .021). All cows (n = 7) with evidence of myocardial necrosis had a cTnI concentration > or = 1.04 ng/mL. cTnI is related to myocardial necrosis and severity of myocardial damage in cattle with monensin toxicosis. cTnI could become a useful diagnostic tool in the noninvasive assessment of myocardial injury in cattle with naturally occurring cardiac disease.

Atypical Acute Monensin Toxicosis and Delayed Cardiomyopathy in Belgian Draft Horses

Atypical Acute Monensin Toxicosis and Delayed Cardiomyopathy in Belgian Draft Horses

Atypical Acute Monensin Toxicosis and Delayed Cardiomyopathy in Belgian Draft Horses

Atypical Acute Monensin Toxicosis and Delayed Cardiomyopathy in Belgian Draft Horses

EFFECTS OF THE IONOPHORE ANTIBIOTIC MONENSIN ON HEPATIC BIOTRANSFORMATIONS AND TARGET ORGAN MORPHOLOGY IN RATS

As a preliminaryin vivoapproach in order to study the mechanism of toxicity of the veterinary anticoccidial monensin, male Wistar rats were orally administered 0, 2 and 12 mg kg−1body wt. day−1of monensin for 7 days. At the end of the experiment, effects of the ionophore on serum creatine kinase, lactic dehydrogenase and selected drug metabolising enzyme activities were investigated. Furthermore, liver, heart andquadriceps femorismuscle samples were submitted to morphological investigations. Clinical signs or increasing levels of enzymic markers of muscle injury attributable to monensin toxicosis have never been observed in treated animals. As a matter of fact all drug metabolising enzymes activities checked have not shown significant changes, except for a significant decrease of ethoxyresorufinO-deethylase (up to 31%) and aminopyrineN-demethylase (17%) activities. Morphologically, mitochondrialcristaefragmentation and initial formation of `myelinic sheaths-like' structures have been noticed in heart and muscle fibres. As far as rat study is concerned, these results confirm heart and muscle as target organs of monensin toxicity. In addition, these findings suggest that the inhibition of hepatic biotransformation processes following the i.p. administration of the ionophore, as reported previously by other authors, might reflect unspecific cellular toxic effects rather than a specific enzyme damage.

Toxicosis in cattle from concurrent feeding of monensin and dried distiller's grains contaminated with macrolide antibiotics.

Consumption of monensin-containing feed contaminated with macrolide antibiotic residues resulted in the death of cattle from multiple feedlots in south-central Kansas. Cattle were fed milo dried distiller's grains (DDG) with solubles from a common source in conjunction with the ionophore antibiotic, monensin. Deaths occurred as early as 72-96 hours after feeding and were preceded by either no premonitory signs or 1 or more of the following: anorexia, depression, dyspnea, locomotor deficits, and recumbency. Significant gross lesions were pulmonary and mesenteric edema, hepatomegaly, and generalized myocardial and skeletal muscle pallor that was confirmed histologically as acute myodegeneration and necrosis. Other significant histologic lesions included centrolobular hepatocellular necrosis, congestion, and pulmonary interstitial and alveolar edema with fibrin exudation. Animals that survived beyond 6 weeks had poor weight gain and coalescing foci of myocardial fibrosis with residual myocardial degeneration. Analysis of trace mineral supplements for monensin were within the manufacturer's label range. The DDG samples from affected feedlots had 50-1,500 ppm of erythromycin, clarithromycin, and related macrolide antibiotic analogues, which originated in the alcohol residue. In a preliminary feeding trial, cattle fed this contaminated DDG in combination with monensin had clinical signs and died with gross and histologic findings comparable to those of the field cases. Even though rations supplemented with the contaminated DDG contained approved levels of monensin, the clinical and postmortem findings were consistent with those expected for monensin toxicosis. The presence of macrolide antibiotic residues in the contaminated feed appeared to affect the biotransformation of otherwise nontoxic levels of monensin, leading to clinical ionophore toxicosis.

A Sudden Death Syndrome Induced in Poults and Chicks Fed Diets Containing Fusarium fujikuroi with Known Concentrations of Moniliformin

A sudden death syndrome was induced in chicks and poults fed diets containing Fusarium fujikuroi, formulated to contain 0-330 mg/kg moniliformin (M) with or without the maximum recommended therapeutic concentration of monensin. Lesions of monensin toxicosis were not observed. Clinical signs were referable to cardiac dysfunction (sudden death, dyspnea, cyanosis, depression). Poults and chicks dying early in the study had no gross lesions or had lesions of right ventricular dilation. Treated poults and chicks dying late in the study or euthanatized at termination of the study had lesions of bilateral myocardial hypertrophy, usually concentric. Absolute heart weights and relative heart weights, expressed as a percentage of body weight, were significantly greater in treated birds than controls (P < 0.05), whereas body weights were significantly less (P < 0.05). Microscopically, lesions progressed from acute myocardial degeneration to necrosis, fibrosis, and hypertrophy. Ultrastructural findings were consistent with the gross and microscopic lesions. Serum pyruvate concentrations were a useful indicator of M-induced cardiotoxicosis. Concentrations of serum pyruvate increased with increased concentration of dietary M, but were not affected by addition of monensin to the diet. In chicks ingesting 40-300 mg/kg M, serum pyruvate concentrations were significantly greater (P > 0.05) than those in controls (controls, 0.28 +/- 0.08 mmol/liter; exposed 0.38 +/- 0.11-0.55 +/- 0.13 mmol/liter). Poults ingesting 80-330 mg/kg M had significantly greater serum pyruvate concentrations than controls (controls 0.33 +/- 0.09 mmol/liter; exposed 0.43 +/- 0.13-1.00 +/- 0.006 mmol/liter). The Vetronics System was used to evaluate electrocardiographic alterations in a limited number of chicks and poults surviving to the end of the feeding trial. Electrocardiographic alterations in poults and chicks fed diets containing > or = 40 mg/kg and > or = 160 mg/kg M, respectively, were consistent with ventricular hypertrophy, myocardial injury, and hypoxia. Electrocardiographic alterations were more striking in poults than in chicks. Altered myocardial metabolism due to M toxicosis, in conjunction with the unusual susceptibility of domestic poultry to altered cardiac metabolism, is believed to be the cause of the organ-specific lesions in these birds. These findings suggest that cardiac injury with subsequent alterations in cardiac electrical conductance may be a cause of the sudden deaths observed in poultry chronically intoxicated with dietary M.

Development of an L6 myoblast in vitro model of moniliformin toxicosis.

L6 myoblasts were used as an in vitro model to investigate the role of moniliformin and its interaction with monensin in turkey knockdown syndrome and sudden death syndromes in poultry. Cell viability and microscopic and ultrastructural alterations noted in L6 myoblasts cultured in the presence of moniliformin (0.0-0.3 microgram/microliter) were compared to those observed in parallel cultures also containing one of the following compounds: selenium (0-0.004 ng/microliter), thiamine (0-0.3 microgram/microliter), or pyruvate (0-0.46 microgram/microliter). Marked dilation of the RER, membranous whorls, glycogen deposition, membrane-bound cytoplasmic inclusions and necrosis were observed in myoblasts exposed to 0.03-0.30 microgram moniliformin/microliter medium. Supplementation of medium with thiamine and pyruvate, or selenium, provided significant protection to cells exposed to 0.0-0.3 microgram/microliter or 0.0-0.15 microgram moniliformin/microliter, respectively. Dose-dependent differences in protein and ATP production were not detected. Myoblasts grown in medium containing 0-0.15 microgram moniliformin/microliter and 7.5-50.0 microM A23187, beauvericin or monensin had degrees of cytotoxicity similar to parallel cultures receiving only an ionophore. L6 myoblasts were a useful model of moniliformin toxicosis. The findings of this study suggest cytotoxicity due to moniliformin in L6 myoblasts may be due in part to oxidative damage and altered pyruvate metabolism, and that moniliformin does not predispose myoblasts to ionophore toxicosis. This study supports the results of in vivo investigations in poultry that moniliformin and monensin do not act synergistically to induce knockdown or monensin toxicosis.

Effects of monensin on selenium status and related factors in genetically hypo- and hyperselenemic growing swine

Summary Monensin is an ionophoretic antibiotic, which selectively transports alkali metal cations across biological membranes. In growing swine, monensin toxicosis causes acute, degenerative cardiac and skeletal myopathy resembling vitamin E-selenium deficiency. Selenium is an essential trace element incorporated in glutathione peroxidase (gsh-Px), an antioxidant enzyme system that protects subcellular membranes. In our study, we examined the effects of monensin on body weight, Se balance, antioxidant status, and serum concentrations of selected minerals in growing pigs that were genetically hypo- or hyperselenemic (hypo-Se and hyper-Se, respectively). Three groups of eight 8-week-old pigs, each comprised of 4 hypo-Se and 4 hyper-Se pigs (76.4 ± 3.0 and 106.3 ± 10.3 ng of Se/ml of serum, respectively), were fed standard diets containing 0.1 mg of supplemental Se/kg of body weight, and either 0, 200, or 400 mg of monensin/kg for a 77-day period, followed by a 28-day monensin withdrawal period. On days 0, 7, 28, 56, 70, and 98, all pigs were weighed and blood was collected for determination of serum gsh-Px, creatine phosphokinase, and aspartate transaminase values, as well as serum concentrations of vitamin E, Se, Ca, Cu, Fe, K, Mg, Na, P, and Zn. Significance of main effects of monensin treatment, genetic Se status, and their interactions was tested by Fisher's variance ratio test, followed by conditional comparison of treatment means with a Bonferroni test. Signs of monensin toxicosis were not observed and monensin consumption had no effect on body weight, or serum creatine phosphokinase, aspartate transaminase, or Se values. However, pigs consuming monensin had consistently higher serum gsh-Px activities, possibly because of increased synthesis of this adaptive antioxidant enzyme. Interactions were not found between monensin and genetic Se status. Hyperselenemic pigs were heavier and had higher serum Se and gsh-Px values than hypo-Se pigs. Furthermore, hypo-Se and hyper-Se pigs were hypo- and hypercupremic, respectively, suggesting genetic regulation of copper status. It is likely that pigs with inadequate antioxidant status (hyposelenemia, hypocupremia) are more susceptible to diseases associated with cellular membrane damage, such as vitamin E-Se deficiency disease and monensin toxicosis.

PROTECTION PROVIDED BY SODIUM SELENITE AGAINST AN ORAL TOXIC DOSE OF MONENSIN IN BROILER CHICKS

Monensin is an ionophoric antibiotic that is widely used in cattle, swine and poultry production. In poultry it is used for its anticoccidial properties. Over the past decade several cases of flock poisoning due to monensin toxicity have been reported. Studies with cattle and swine demonstrate that Se-vitamin E pretreatment can provide a protective effect from an induced monensin toxicosis. In this study, 192 male broiler chicks were given one of eight diets, varying in the concentration of supplemented Se, as sodium selenite, from 0.5 to 15.0 mg kg−1, for a period of 4 wk. An oral dose of monensin sufficient to cause mortality, in the absence of a protective effect, was then given. It was observed that moderate levels of sodium selenite pretreatment did provide a protective effect from monensin toxicosis, expressed in terms of reduced morbidity and mortality. The concentrations needed to provide this protection, however, are above those recommended for dietary supplementation in broiler diets. For this reason more research on the interactions between monensin and Se and monensin and vitamin E needs to be conducted to find a means of protection from the potential threat of monensin toxicity in broiler flocks. Key words: Monensin, sodium selenite, broilers, toxicity

Nutritional myopathy in cattle associated with monensin toxicosis.

Nutritional myopathy in cattle associated with monensin toxicosis.

Light and electron microscopic changes in cardiac and skeletal muscle of sheep with experimental monensin toxicosis.

Monensin toxicosis was induced in lambs by either a single oral dose of 12 mg/kg or six daily doses of 8 mg/kg. Clinical signs of toxicosis consisted of depression, dyspnea, stiffness of gait, reluctance to move, and recumbency. Serum creatine phosphokinase activity was increased. Samples of skeletal and cardiac muscle were obtained over a six-day period and examined by light and electron microscopy. Light microscopic changes in cardiac and skeletal muscles consisted initially of vacuolation and intracellular edema of muscle cells followed by segmental necrosis. Interstitial fibrosis was present on days 5 and 6 postexposure. Muscle fiber necrosis was more severe in skeletal than cardiac muscles and most severe in sheep given 8 mg/kg of monensin daily. Macrophages were seen only in areas of severe necrosis. The earliest ultrastructural change was severe swelling of mitochondria. Secondary changes consisted of lipid accumulation and myofibrillar alterations. Myoblast proliferation was present as early as four days after initial exposure to monensin.