monensin and Acute-Disease

Myoglobinuria or rhabdomyolysis occurs when myoglobin escapes into the blood and then into the urine after acute muscle necrosis. It can be a serious medical condition leading to renal failure and death. There are many causes including exertion, crush syndromes, ischaemia, metabolic disorders, exogenous toxins and drugs, heat stroke and hereditary disorders such as malignant hyperthermia. We report the case of a 17 year-old boy who developed myoglobinuria, renal failure and death 11 days after ingesting sodium monensin, possibly with the intention of developing muscles. Sodium monensin, the active principle of Rumensin(R), is a dietary additive used as a growth promoter for confined cattle. There are no previous reports of human intoxication. Accidental or experimental sodium monensin intoxication in animals produces similar findings to those seen in this case.

Topics: Acute Disease; Acute Kidney Injury; Adolescent; Fatal Outcome; Food Additives; Humans; Male; Monensin; Muscle Development; Rhabdomyolysis

The effect of feeding monensin, with or without dry hay plus wilted forage, on ruminal formation of 3-methylindole (3MI) was investigated in pastured cattle. Eighty-two cows were allotted to 3 groups. Cows of group-1 served as controls and were given a daily energy supplement (1 kg/head) without monensin for 1 day before and for 7 days after being allowed access to lush pasture. Cows of groups 2 and 3 were given the same daily energy supplement, which also contained monensin (200 mg/kg of supplement). Cows of group 3 also were fed dry hay for 5 days before the start of the study and continued to be given supplemental hay for 4 days after being allowed access to lush pasture containing a layer of wilted forage. Ruminal 3MI and indole concentrations increased on day 1 after all groups were allowed access to lush pasture. By day 7, 3MI concentration in all cows had decreased to pregrazing concentration. Indole concentration did not reach pregrazing concentration until day 10 for cows of groups 1 and 2. Group-3 cows had pregrazing indole concentration on day 7. Ruminal indole concentration did not differ (P greater than 0.05) between groups 1 and 2. Ruminal indole concentration was lower (P less than 0.01) in group-3 cows on all sample collection days, except day 10, compared with that in the other groups. Monensin reduced (P less than 0.01) 3MI formation on days 1 and 7 in group-2 cows, compared with group-1 cows. Group-3 cows had lower 3MI concentration than did group-1 cows (P less than 0.01) on days -1, 1, 4, and 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Animal Feed; Animals; Cattle; Cattle Diseases; Digestion; Fatty Acids, Volatile; Female; Hydrogen-Ion Concentration; Indoles; Monensin; Poaceae; Pulmonary Edema; Pulmonary Emphysema; Random Allocation; Rumen; Skatole

Topics: Acute Disease; Animals; Cardiomyopathy, Dilated; Cattle; Cattle Diseases; Female; Monensin; Selenium

Investigations were carried out with pigs divided into four groups and treated with monensin-Na at rates of 20, 30, and 50 mg/kg, once only, through a nose-pharyngeal tube. The total change in the clinical status was followed up. Most characteristic were found to be the changes setting in with the posture and locomotive apparatus--prolonged lying, pareses, etc. Blood was checked in the dynamic course of the disease at the 4th and the 24th hour as well as on the 6th day following monensin-Na treatment. The amount of haemoglobin and the erythrocyte count rose in the early stage of intoxication, and came back to normal after the 24 th hour. Leukocytosis with neutrophilia was also found. The serum level of selenium, calcium, vitamins A, B1, and C dropped substantially, while that of phosphorus and magnesium rose. The morphologic changes were found to be localized in the parenchymal organs and in the skeletal muscles. Featuring were diffuse hyperaemia, haemorrhages, granular degeneration, and focal necrosis.

Topics: Acute Disease; Animals; Blood Cell Count; Blood Chemical Analysis; Dose-Response Relationship, Drug; Hemoglobins; Monensin; Swine; Swine Diseases; Time Factors

Monensin, A Na+-selective carboxylic ionophore, produces left atrial damage in pigs given toxic doses. Eight weanling pigs were given mycelial monensin orally (40 mg/kg body weight) and were killed on days 1, 2, 4, and 16 (two animals at each time interval) for ultrastructural study of the left atrial lesions. On days 1-4, extensive necrosis with contraction bands was present. Rapid macrophagic invasion and phagocytosis of sarcoplasmic debris was seen on days 2 and 4. Missing necrotic myocytes were outlined by persistent "tubes" of external laminas. In some surviving myocytes, sublethal injury was evident on day 1 by mitochondria with condensed conformation and on days 2, 4, and 16 by moderate to marked myofibrillar lysis and sarcoplasmic vacuolation. Monensin cardiotoxicity in pigs constitutes a unique example of selective injury to atrial myocardium.

Topics: Acute Disease; Animals; Cardiomyopathies; Cattle; Dose-Response Relationship, Drug; Female; Furans; Heart Atria; Macrophages; Male; Monensin; Myocardial Contraction; Myocardium; Necrosis; Swine

Large doses of monensin, a Na+-selective carboxylic ionophore, produce polyfocal, monophasic necrosis of skeletal muscle, with Type I fiber selectivity, in swine. For a study of the sequential ultrastructural alterations in affected skeletal muscles, 14 weanling pigs were given 40 mg monensin/kg body weight and were euthanatized 1, 2, 4, 8, and 16 days later. Myotoxicosis and myoglobinuria were apparent clinically. At necropsy, white, dry areas of necrosis were present in the muscle masses of the anterior and posterior thigh, shoulder, and loin. Two patterns of skeletal muscle necrosis were observed on Day 1, especially in Type I fibers. In fibers exhibiting the first of these patterns, the contractile material was disrupted, forming dense amorphous and filamentous clumps scattered within the persistent sheaths of external lamina (sarcolemmal tubes); the mitochondria were swollen and contained flocculent matrix densities, and the nuclei were pyknotic. Fibers showing the second pattern were uniformly dense, but their sarcoplasm was not disrupted. Sublethally injured fibers were also observed and showed focal myofibrillar lysis. On Days 2 and 4, the necrotic muscle had marked infiltration of macrophages in the interstitium and within sarcolemmal tubes. Rapid resolution of the fiber necrosis occurred by phagocytosis of the sarcoplasmic debris. Regeneration of affected muscles developed early following injury and progressed rapidly to complete restoration of the necrotic muscles without residual fibrosis. Regeneration was initiated on Day 1 by activation of satellite cells to form presumptive myoblasts; on Days 4 and 8 these cells showed evidence of fusion, forming myotubes to restore the necrotic fibers.

Topics: Acute Disease; Animals; Female; Furans; Male; Mitochondria, Muscle; Monensin; Muscle Contraction; Muscles; Muscular Diseases; Necrosis; Regeneration; Sarcoplasmic Reticulum; Swine

Monensin was administered orally to 3 sheep at dosages of 12 (the LD50), 16, and 24 mg/kg of body weight, respectively. Clinical signs of monensin toxicosis were observed in the sheep in 24 to 36 hours of administration. Clinical signs included CNS depression, anorexia, diarrhea, and stiffness. Increased serum creatine phosphokinase and aspartate aminotransferase activities identified possible muscle damage. Sheep were euthanatized at 54 hours after dosing; at necropsy, there were skeletal muscle hemorrhages, pale myocardium, and pulmonary edema. Ultrastructural lesions were in the liver, diaphragm, and myocardium; diaphragm and myocardium were most severely affected. Mitochondrial swelling and cristolysis, swollen sarcoplasmic reticulum, and disruption of myofibrillar architecture were prominent. These ultrastructural changes are consistent with the hypothesis that monensin causes muscle cell necrosis due to its ionophorous properties and disruption of cellular Na+:Ca2+ balance. It is proposed that this upset of normal ionic processes allows increased intracellular calcium, which directly leads to the functional and structural mitochondrial changes observed.

Topics: Acute Disease; Animals; Female; Furans; Kidney; Liver; Male; Monensin; Muscles; Myocardium; Sheep; Sheep Diseases

Twenty beef calves weighing approximately 180 kg were allotted to 3 groups. In group A, 6 calves were given 25 mg of mycelial monensin/kg of body weight orally and were evaluated at 1, 2, and 4 days for clinical, ECG, clinicopathologic, and pathologic alterations. In group B, 7 calves were given a single dose of monensin (40 mg/kg) and 5 were given a 2nd 40 mg/kg dose on day 7; calves were evaluated at days 1, 2, 4, 7, 8, 9, and 11. In group C, 2 calves served as controls. Monensin-treated calves developed anorexia, diarrhea, and lethargy after day 1. One group B calf died on day 7 with lesions of congestive heart failure. Electrocardiographic abnormalities were not observed in group A calves; in group B, prolongation of Q-T and QRS intervals occurred from days 2 to 11 and first degree heart block was seen from days 7 to 11. Clinicopathologic alterations included: increased serum activities of aspartate aminotransferase and creatine kinase in group B calves after day 2; decreased serum K+, Na+, and Ca2+ concentrations in both groups, and postdosing occurrence of leukocytosis. Calves were euthanatized sequentially and the lesions of monensin toxicosis were present in the heart, skeletal muscles, and rumen in groups A and B. Disseminated pale yellowish-brown areas of necrosis were present in the ventricular myocardium of 6 of 12 group B calves. Gross lesions were not present in the skeletal muscles or rumen. Microscopically, the myocardial and skeletal muscular lesions were characterized by sarcoplasmic vacuolation from mitochondrial swelling and lipid accumulation in calves killed after day 1 in groups A and B, and by myocardial necrosis with contraction bands, but without calcification, in group B calves killed by day 4. Acute rumenitis was present in groups A and B calves. Myotoxic effects of monensin may be related to its action as an ionophore producing altered intracellular ion concentrations and initiating degeneration and necrosis in striated muscle fibers.

Topics: Acute Disease; Animals; Cassia; Cattle; Cattle Diseases; Diagnosis, Differential; Female; Furans; Heart; Male; Monensin; Muscles; Myocardium; Necrosis; Plant Poisoning; Plants, Medicinal; Rumen; Selenium; Vitamin E Deficiency