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Journal of Animal Science Jul 1981Four feeding trials were conducted to determine (1) how the organophosphate ronnel affects thyroid and adrenal circulating hormone levels and blood profile measurements...
Four feeding trials were conducted to determine (1) how the organophosphate ronnel affects thyroid and adrenal circulating hormone levels and blood profile measurements of beef steers and (2) whether the effects of ronnel observed in beef steers could be produced in growing rats. In trial 1, four groups of eight steers each were given either no ronnel or 4 mg ronnel/kg body weight daily in diets fed at either limited (1.8% of body weight) or ad libitum intake. After 7 weeks, intake levels, but not ronnel treatments, were reversed during a 1-week transition period, and feeding was continued for another 7 weeks. In trial 2, four groups of six steers each were given 0, 44, 88 or 176 ppm ronnel premixed in diets fed ad libitum for 18 weeks. Actual ronnel intakes averaged 0, 1.01, 2.12 and 4.73 mg/kg body weight daily in trial 2. In trials 3 and 4 , growth and intake were measured in 64 and 32 growing Sprague-Dawley rats, respectively, fed levels of ronnel ranging from 0 to 100 ppm in the diet. In trial 3, blood plasma was analyzed at various times for triiodothyronine (T3), thyroxine (T4), cholesterol and total lipid content. In trial 1, the concentration of Plasma T4 was 1.31 times higher in steers fed ronnel that in control steers. In trial 2, plasma T4 was 1.30 times higher in steers fed 176 ppm ronnel, the level that improved growth, than in steers fed the lower ronnel levels. Circulating levels of T3, cortisol and aldosterone were similar for both control and ronnel-fed steers. Serum cholesterol concentrations were consistently higher in ronnel-fed steers. The data indicated that the growth-promoting effect of ronnel in steers may be associated with a shift in thyroid function. Effects of ronnel in steers were not observed in rats, demonstrating a species difference between steers and rats.
Topics: Aldosterone; Animals; Cattle; Endocrine Glands; Growth; Hydrocortisone; Male; Organothiophosphorus Compounds; Rats; Rats, Inbred Strains; Thyroxine; Triiodothyronine
PubMed: 6172413
DOI: 10.2527/jas1981.531217x -
Journal of Animal Science Mar 1985Ronnel [0,0-dimethyl 0-(2,4,5-trichlorophenyl) phosphorothioate] is an organophosphate pesticide with growth-promoting properties. Experiments were conducted to...
Ronnel [0,0-dimethyl 0-(2,4,5-trichlorophenyl) phosphorothioate] is an organophosphate pesticide with growth-promoting properties. Experiments were conducted to determine effects of ronnel on oxidation of and fatty acid synthesis from acetate and glucose as indices of metabolic activity in subcutaneous adipose tissue and skeletal muscle from 6-, 12- and 18-mo-old steers. Ronnel depressed metabolic activity in adipose tissue from 6- and 12-mo-old steers without concomitantly decreasing metabolic activity in skeletal muscle. Production of CO2 and fatty acids from acetate and glucose in tissues from 18-mo-old steers was influenced less by ronnel than in tissues from younger steers. Interactions of ronnel with thyroxine or growth hormone on acetate oxidation and conversion to fatty acids in adipose tissue also were investigated. Thyroxine increased acetate oxidation and decreased fatty acid synthesis. Ronnel interfered with the metabolic effects of thyroxine. Growth hormone, with or without ronnel, did not affect metabolic activity of adipose tissue. Ronnel seemingly alters the partitioning of acetate and glucose between major metabolic processes in adipose tissue and skeletal muscle.
Topics: Acetates; Acetic Acid; Adipose Tissue; Animals; Carbon Dioxide; Cattle; Culture Techniques; Fatty Acids; Food Additives; Glucose; Glycerol; Growth Hormone; Male; Muscles; Organothiophosphorus Compounds; Oxidation-Reduction; Thyroxine
PubMed: 2580822
DOI: 10.2527/jas1985.603652x -
Journal of Animal Science Jul 1985This study compares in vitro effects of propylthiouracil (PTU) and ronnel on the conversion of thyroxine (T4) to triiodothyronine (T3) in liver and kidney from Angus... (Comparative Study)
Comparative Study
This study compares in vitro effects of propylthiouracil (PTU) and ronnel on the conversion of thyroxine (T4) to triiodothyronine (T3) in liver and kidney from Angus steers. Tissues were homogenized and incubated with T4 (1.3 microM) in the presence of 0 to 59 microM PTU or 0 to 49.7 microM ronnel. The T3 generated during a 30-min incubation was measured by radioimmunoassay. It was found that 1.47, 5.9 and 59 microM PTU decreased T4 to T3 conversion in liver and kidney by 62 and 88, 71 and 100, and 81 and 100%, respectively. The inhibition caused by 1.47 and 5.9 microM PTU was overcome by addition of 2 mM dithiothreitol (DTT). Ronnel in concentrations of 1.24, 6.22, 49.7 microM decreased T4 to T3 conversion in liver and kidney 46 and 45, 51 and 72, and 78 and 95%, respectively. However, with ronnel, the addition of DTT caused further inhibition. A Lineweaver-Burk plot of the data obtained using .32 to 6.43 microM T4 with 1.47 and 5.9 microM PTU or 6.22 and 12.44 microM ronnel indicated that PTU is an uncompetitive inhibitor (Ki = 1.67 microM) and ronnel is a noncompetitive (Ki = 15.5 microM) inhibitor of T4-5'-monodeiodination. The data suggest that decreased conversion of T4 to T3 by PTU or ronnel may be responsible for the increased plasma concentrations of T4 and slightly decreased plasma concentrations of T3 reported in steers treated with levels of both PTU and ronnel that are associated with growth stimulation.
Topics: Animals; Cattle; Dithiothreitol; Food Additives; In Vitro Techniques; Iodide Peroxidase; Kidney; Liver; Male; Organothiophosphorus Compounds; Peroxidases; Propylthiouracil; Radioimmunoassay; Thyroxine; Triiodothyronine
PubMed: 2411706
DOI: 10.2527/jas1985.611197x -
Journal of Animal Science Jan 1983An experiment with eight beef steers was conducted to determine the patterns of change for plasma concentrations of thyroxine (T4), triiodothyronine (T3), cholesterol...
An experiment with eight beef steers was conducted to determine the patterns of change for plasma concentrations of thyroxine (T4), triiodothyronine (T3), cholesterol and total lipid following the addition or withdrawal of the organophosphate, ronnel, from the diet. Steers were fed 0, 2, 4 and 8 mg ronnel/kg body weight daily in a Latin square arrangement of treatments with five 28-d periods. Plasma samples were obtained at -2, 1, 3, 5, 7, 9, 16 and 23 d of each period. Steers had not received ronnel before period 1 and, for periods 2 to 5, steers previously fed the lower levels (0 and 2 mg ronnel) were switched to the higher levels (4 and 8 mg ronnel) and steers previously fed the higher levels were switched to the lower levels. Treatment assignments for periods 1 and 5 were the same. Feed intake was similar for all treatments (7.8 kg/d) and daily gain was greater when ronnel was fed (.65 vs .88 kg). Plasma T4 concentrations increased positively in response to ronnel level within the first day after ronnel feeding began and reached a plateau within 3 d. Plasma T4 concentrations decreased following the withdrawal of ronnel, but the response was slower; a lower level being established within about 7 d. Changes in plasma T3 concentrations were small, but were concurrent with plasma T4 changes and were inversely related to ronnel level. Plasma cholesterol concentrations tended to be positively related to ronnel level, but changed slowly with time; plasma total lipid concentrations were not consistently affected by ronnel level. The results of this experiment demonstrate that ronnel has an immediate effect on thyroid function in beef steers.
Topics: Animals; Body Weight; Cattle; Cholesterol; Food Additives; Lipids; Male; Organothiophosphorus Compounds; Thyroxine; Triiodothyronine
PubMed: 6186657
DOI: 10.2527/jas1983.561125x -
Journal of Toxicology and Environmental... Jul 1982Insecticidal formulations in the form of dusts or aerosols containing rotenone from the root of Derris elliptica and pyrethrum from the flower of Chrysanthemum...
Insecticidal formulations in the form of dusts or aerosols containing rotenone from the root of Derris elliptica and pyrethrum from the flower of Chrysanthemum cinerariaefolium are commonly used in homes and gardens. Ronnel (fenchlorphos), a systemic insecticide, is used to control house flies and, upon oral treatment, ectoparasites of cattle. These insecticides are extensively used and their teratologic potential has not been fully investigated. Technical grades of rotenone at 0, 2.5, 5, or 10 mg/kg, pyrethrum at 0, 50, 100, or 150 mg/kg (rotenone and pyrethrum were of natural origin) and ronnel at 0, 400, 600 or 800 mg/kg were tested. Each of these was suspended in corn oil and administered orally in single daily doses on d 6-15 of pregnancy to Wistar rats. The dams were killed on the last day of pregnancy, and all fetuses were evaluated following routine teratologic methods. Rotenone was associated with an increased number of nonpregnant rats and resorptions, at a dose of 10 mg/kg; reductions in maternal body weight gain, fetal weight, and skeletal ossification, together with an increased incidence of extra rib, were found at 5 and 10 mg/kg; but no significant effects were found at 2.5 mg/kg. Increases in the incidence of resorptions in pyrethrum-treated groups and of extra rib in ronnel-treated groups were also observed.
Topics: Animals; Chrysanthemum cinerariifolium; Female; Gestational Age; Organothiophosphorus Compounds; Pregnancy; Rats; Rats, Inbred Strains; Rotenone; Teratogens
PubMed: 6182301
DOI: 10.1080/15287398209530235 -
The Journal of the Florida Medical... Sep 1966
Topics: Child; Child, Preschool; Humans; Infant; Insecticides; Larva Migrans; Phosphates
PubMed: 5911107
DOI: No ID Found -
Archives of Environmental Contamination... 1977Two beef cattle feedlot experiments were conducted to determine the amount of certain agricultural chemicals that are likely to be found in both fresh and stored feedlot...
Residue content of beef feedlot manure after feeding diethylstilbestrol, chlortetracycline and Ronnel and the use of stirofos to reduce population of fly larvae in feedlot manure.
Two beef cattle feedlot experiments were conducted to determine the amount of certain agricultural chemicals that are likely to be found in both fresh and stored feedlot manure and to investigate fly control in this manure. In experiment 1, diethylstilbestrol (DES), chlortetracycline (CTC), and ronnel were used as feed additives. Fresh manure, stored manure, runoff water, manure weathered on pasture, and soil from pasture fertilized with manure were analyzed for these additives. Stirofos was added to fresh manure as a larvicide for fly control. In experiment 2, the residue aspects of DES and CTC were repeated. In this experiment, stirofos instead of ronnel was fed with DES and CTC. Sixty-eight percent of the DES fed to cattle appeared in fresh manure and 52% in manure stored for 12 weeks. Comparable percentage values were 17 and 11% for CTC and 13 and 3% for ronnel; somewhat less DES and CTC were found when a concentrate diet was fed. Detectable amounts of DES, ACT, and ronnel were not found in runoff water, weathered manure, or soil. Adding an emulsifiable concentrate formulation of stirofos directly to manure at a rate of approximately 45 ppm of wet manure completely controlled the larvae of house fly (Musca domestica L.) whereas feeding stirofos at a rate of 1.5 mg per kg of body weight daily reduced larval counts 82% in manure from forage-fed heifers and 63% in manure from concentrate-fed heifers. Stirofos was not detected in runoff water, weathered waste, or soil.
Topics: Animal Feed; Animals; Cattle; Chlortetracycline; Diethylstilbestrol; Diptera; Feces; Food Additives; Insecticides; Larva; Male; Organothiophosphorus Compounds; Pesticide Residues; Sewage; Soil
PubMed: 71021
DOI: 10.1007/BF02097761 -
PloS One 2018Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA damage...
Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA damage and phosphorylates many proteins, including those involved in DNA repair, cell cycle control, and apoptosis. Characteristic biological and molecular functions of ATM observed in mammals are conserved in Drosophila melanogaster. As an example, conditional loss-of-function ATM alleles in flies cause progressive neurodegeneration through activation of the innate immune response. However, unlike in mammals, null alleles of ATM in flies cause lethality during development. With the goals of understanding biological and molecular roles of ATM in a whole animal and identifying candidate therapeutics for A-T, we performed a screen of 2400 compounds, including FDA-approved drugs, natural products, and bioactive compounds, for modifiers of the developmental lethality caused by a temperature-sensitive ATM allele (ATM8) that has reduced kinase activity at non-permissive temperatures. Ten compounds reproducibly suppressed the developmental lethality of ATM8 flies, including Ronnel, which is an organophosphate. Ronnel and other suppressor compounds are known to cause mitochondrial dysfunction or to inhibit the enzyme acetylcholinesterase, which controls the levels of the neurotransmitter acetylcholine, suggesting that detrimental consequences of reduced ATM kinase activity can be rescued by inhibiting the function of mitochondria or increasing acetylcholine levels. We carried out further studies of Ronnel because, unlike the other compounds that suppressed the developmental lethality of homozygous ATM8 flies, Ronnel was toxic to the development of heterozygous ATM8 flies. Ronnel did not affect the innate immune response of ATM8 flies, and it further increased the already high levels of DNA damage in brains of ATM8 flies, but its effects were not harmful to the lifespan of rescued ATM8 flies. These results provide new leads for understanding the biological and molecular roles of ATM and for the treatment of A-T.
Topics: Alleles; Animals; Ataxia Telangiectasia Mutated Proteins; DNA Damage; Drosophila Proteins; Drosophila melanogaster; Drug Evaluation, Preclinical; Female; Genes, Insect; Genes, Lethal; Immunity, Innate; Male; Mutation; Nerve Degeneration; Organothiophosphorus Compounds; Phenotype; Protein Serine-Threonine Kinases
PubMed: 29338042
DOI: 10.1371/journal.pone.0190821 -
Journal of Neurochemistry Nov 1982This paper describes the effect of the organophosphorus compound, the oxygen analogue of ronnel (OAR), on the activity of some membrane-bound enzyme systems in the brain...
This paper describes the effect of the organophosphorus compound, the oxygen analogue of ronnel (OAR), on the activity of some membrane-bound enzyme systems in the brain mitochondria of developing, young-adult, and old rats. Age-related changes were noted in the cholesterol-to-protein ratio, whereas the phospholipid content in mitochondria showed little change during development as well as aging. The results obtained suggest that development of brain succinate dehydrogenase may consist in a decrease of Km and increase of Vmax values. In aged rats an altered, perhaps inhibited form of the enzyme is produced. The oxygen analogue of ronnel caused a mixed-type inhibition of the succinate dehydrogenase derived from brains of 4-day-old, 16-day-old and 2-month-old animals. In the case of enzyme from the brain of 18-month-old rats, a typical competitive-type inhibition was observed. Mechanisms responsible for inhibition of the succinate: cytochrome c reductase from brains of developing animals are similar to those for succinate dehydrogenase. In aged rats (18 months old), however, a noncompetitive mechanism of inhibition of succinate: cytochrome c reductase was revealed. The experiments reported here provide evidence that lipid-soluble molecules of OAR may interact with membrane phospholipids and lead to modification of membrane architecture and also of enzyme kinetic behaviour. It may be also concluded, that the sensitivity of the enzyme systems studied to inhibition by OAR is an age-dependent phenomenon. Modification of membrane by development or aging alters the kinetics as well as the sensitivity of enzymes to inhibitors.
Topics: Aging; Animals; Brain; Cholesterol; Female; Kinetics; Male; Mitochondria; Organothiophosphorus Compounds; Phospholipids; Proteins; Rats; Rats, Inbred Strains; Succinate Cytochrome c Oxidoreductase; Succinate Dehydrogenase
PubMed: 6181202
DOI: 10.1111/j.1471-4159.1982.tb12571.x -
Journal of the American Veterinary... Jun 1976Of 20 dogs with generalized demodicosis, 18 responded favorably to treatment with 8.5% ronnel solution applied to one-third of the body every 3rd day, in rotation.... (Clinical Trial)
Clinical Trial
Of 20 dogs with generalized demodicosis, 18 responded favorably to treatment with 8.5% ronnel solution applied to one-third of the body every 3rd day, in rotation. Duration of treatment was from 5 to 20 weeks. In 2 dogs, the demodicosis recurred and required additional treatment with ronnel. Two dogs died during the study. One death was attributed to ronnel toxicosis; the other was unexplained. Eight of 10 control dogs treated orally and topically for pyoderma associated with demodicosis still had demodicosis 1 year after initiation of the study.
Topics: Animals; Clinical Trials as Topic; Dog Diseases; Dogs; Female; Male; Mite Infestations; Organothiophosphorus Compounds; Pyoderma; Remission, Spontaneous
PubMed: 58853
DOI: No ID Found