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Chlordecone (CAS 143-50-0)




  • 1.
    Book/Book Chapter
    Book/Book
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    Cardiac bioenergetics as biomarkers for insecticides toxicity .2. In vivo effects of chlordecone on adenine nucleotide pool metabolism and cyclic-AMP levels in rat myocardium, liver, kidney, brain and skeletal muscle

    Author: Abdelfattah, ASA
    (1996) 179-194.
    Minus Sign. Click to see only selected choices. Background: Chlordecone (kepone(11)), 1, 1a, 3, 3a, 5, 5a, 5, 5b, 6-deca chlorooctahydro 1, 3, 4-metheno-2H-cyclobutal . . . Plus Sign. Click to expand choices. Background: Chlordecone (kepone(11)), 1, 1a, 3, 3a, 5, 5a, 5, 5b, 6-deca chlorooctahydro 1, 3, 4-metheno-2H-cyclobutal (Cd)-pentalen-2-one, is an organochlorine insecticide which was extensively used to control fire ants in the southern regions of the United State. Accidental exposure to chlordecone resulted in severe tremors, incoordination, blurring vision and ataxia in humans. Despite of several reports, the mechanisms of toxic action of chlordecone has not elucidated. Chlordecone has been shown to be a potent inhibitor of several ATP-dependent reactions. In the preceding study, we found that chlordecone is a potent inhibitor of mitochondrial ATPase activity and the inhibition site was identified as the oligomycin-sensitivity conferring protein (OSCP).

    Rationale: We tested whether administration of chlordecone affects tissue bioenergetics, i.e., ATP pool metabolism, by either inhibiting mitochondrial ATPase when catalyzes ATP synthesis or catalyses ATP hydrolysis or both, in vivo.

    Methods: Rats received a single oral does of chlordecone (200 mg/kg in corn oil) by intubated lavage. Early signs of intoxication were recorded. After 6 hours, animals were decapitated and different tissues were quickly dissected and frozen in liquid nitrogen. Tissue samples were extracted and analyzed by the HPLC to measure ATP, ADP, AMP, adenosine, inosine, hypoxanthine, xanthine, cAMP and NAD(+) levels.

    Results: Early signs of chlordecone-induced neurotoxicity were evident 2 hours following oral administration and characterized by severe and prolonged tremors upon anxiety or stimulation and muscular spasticity. In a preliminary study, a single oral dose of chlordecone (200 mg/kg) caused a 100% mortality after 24 hours of administration (n = 16). Despite of severe signs of chlordecone-induced neurotoxicity, none of the animals have died 6 hours after administration. Chlordecone induced significant loss of tissue ATP levels in rat myocardium (p < 0.001, n = 9), brain (p < 0.01, n = 16), liver (p < 0.05, n = 10). and kidney (p < 0.001, n = 9) compared to the untreated control-group. ATP levels were not significantly reduced in skeletal muscle. ADP levels were significantly reduced in the liver (p < 0.5), kidney (p < 0.001) and the brain (p < 0.01) compared to the control group. A significant decline in the level of cAMP was observed mainly in the liver (p < 0.005 vs the control group). Chlordecone differentially reduced the total adenine nucleotide, nucleoside, purine, cAMP and NAD(+) pool compared to the control group.

    Conclusion: Chlordecone significantly reduced the steady state levels of adenine nucleotide pool suggesting that it is not only inhibit ATP utilization but also impairs ATP synthesis. Results from this study document that variable tissue sensitivity to chlordecone poisoning. These tissue-related differences may be due to variable energy requirements and reserve in different tissues as well as the number, size and the efficiency of mitochondria to produce ATP.
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  • 2.
    Book/Book Chapter
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    Cardiac bioenergetics as biomarkers for organochlorine insecticides toxicity .1. Chlordecone: A potent inhibitor of rat cardiac muscle mitochondrial ATPase complex (F-1/F-0)

    Authors: Abdelfattah, ASA; Koch, RB
    (1996) In Mansour, S (Ed.), Proceedings of the 3rd congress of toxicology in developing countries - together for immune and environmental welfare (pp. 153-166). Cairo, Egypt: National Research Center, Dokki.
    Minus Sign. Click to see only selected choices. Background. Chlordecone is a potent inhibitor of ATPases. The subcellular mechanism of action of chlordecone . . . Plus Sign. Click to expand choices. Background. Chlordecone is a potent inhibitor of ATPases. The subcellular mechanism of action of chlordecone on ATPases is not known.

    Rational. The present study was designed to investigate the mechanism(s) by which mitochondrial oligomycin-sensitive (OS) Mg2+-ATPase complex (F1F0-ATPase) is inhibited by chlordecone compared to Na+-K+-ATPase and Ca2+-ATPase.

    Methods. Mitochondrial ATPase activity and sensitivity to chlordecone was determined in crude mitochondrial preparations, soluble mitochondrial particles and soluble F-1-ATPase preparation in cardiac muscle preparations obtained from different species and from various tissue preparations of the rat species. Na+-K+-ATPase and Ca2+-ATPase activity was determined in crude of partially purified preparations.

    Results. Among different species, the rat heart mitochondrial preparations had the highest OS-ATPase activity and were the most sensitive to chlordecone. The inhibition of rat heart OS-ATPase was kinetically noncompetitive with respect to the substrate (ATP) concentrations. The apparent inhibition constant was 10 and 50 nM. The specific activities of OS-ATPase in rat liver mitochondrial preparations were 5 fold less than that of the rat heart. Solubilisation of rat heart F-1/F-0 ATPase from the inner mitochondrial membrane by a sequential treatment with detergents resulted in complete retention of the oligomycin, DCCD and azide sensitives which indicated the intactness of the F-1/F-0 ATPase complex. Detachment of the soluble F-1-ATPase from rat heart F-1/F-0) complex, resulted in a complete loss of enzyme sensitivity to chlordecone, DDT, Oligomycin, and DCCD. These results emphasise the essential requirement for the oligomycin sensitivity conferring protein and the membranous component (F-0) in order to both chlordecone and oligomycin sensitivities to F-1-ATPase. Chlordecone also inhibited N+-K+-ATPase and Ca2+-ATPase activities but by less degree than mitochondrial ATPase.

    Conclusions. It is concluded that chlordecone interacts with mitochondrial OS-ATPase complex as fully integrated unit and possibly by a similar mechanism to that of oligomycin.
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  • 3.
    Technical Report
    Technical
    Report
    CHLORDECONE INDUCES IN-VIVO DEPRESSION OF ATP PRODUCTION UTILIZATION AND METABOLISM IN RAT MYOCARDIUM BRAIN LIVER KIDNEY AND SKELETAL MUSCLE

    Authors: Abd-Elfattah, AS; Koch, RB; Godwin, CK; Salter, DR; Wechsler, AS
    (1985) (21-26). (BIOSIS/85/04702).
    Abstract: BIOSIS COPYRIGHT: BIOL ABS. RRM ABSTRACT SODIUM PUMP CALCIUM PUMP NEUROTRANSMITTER RELEASE
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  • 4.
    The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
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    Article
    Ploidy patterns in hepatic tumors induced by Mirex

    Authors: Abraham, R; Benitz, KF; Mankes, R
    (1983) Experimental and Molecular Pathology 38:271-282.
    Minus Sign. Click to see only selected choices. The effects of chronic exposure to dietary Mirex was investigated in rat livers over a 13 month period. . . . Plus Sign. Click to expand choices. The effects of chronic exposure to dietary Mirex was investigated in rat livers over a 13 month period. The distribution of ploidy (diploid and tetraploid nuclei) in nodular and nonnodular areas was analyzed in a Coulter Counter fitted with a Channelizer. The nodules, such as adenomas and carcinomas, were identified in histologic sections obtained from companion samples, part of which was used for analysis of nuclear ploidy. The carcinogen disturbed the distribution of nuclei in the ploidy classes, selectively reducing the number of tetraploid cells. This reduction in tetraploid cells corresponded to the nature of the tumor, the most significant effect being noted in hepatocellular carcinomas.
    Tagged With: 06/2015 Litsearch Results, ToxNet
  • 5.
    Technical Report
    Technical
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    Species differences in the hepatic response to insecticides

    Authors: Abraham, R; Fulfa, J; Mayes, B; Coulston, F
    (1977)
    Minus Sign. Click to see only selected choices. PESTAB. The livers of monkeys, rats and mice were examined over a period of 3 yr to determine species . . . Plus Sign. Click to expand choices. PESTAB. The livers of monkeys, rats and mice were examined over a period of 3 yr to determine species response differences to mirex. Mirex was administered by stomach tube to rhesus monkeys at 5 and 20 ppm for 6 days/wk for up to 3 yr. Mice were given mirex at levels of 1 and 5 ppm and rats received 5 ppm. Acid phosphatase (AcPase) and glucose-6-phosphatase (G-6-Pase) activities were not changed in livers of mice receiving 1 ppm. G-6-Pase activity decreased in the centrilobular areas of mouse livers while AcPase activity increased with time in the 5 ppm group. Rat livers had no increased in AcPase activity and only a marginal loss in G-6-Pase activity. Monkey livers demonstrated no loss of G-6-Pase or activation of AcPase. The underlying feature in all livers was proliferation of smooth endoplasmic reticulum.
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  • 6.
    The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
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    Individual and combined effects of mirex and polychlorinated biphenyls on mouse liver-cells

    Authors: Abraham, R; Koepke, UC; Goldberg, L; Coulston, F
    (1974) Toxicology and Applied Pharmacology 29:128-129.
    Minus Sign. Click to see only selected choices. Liver enlargement, proliferation of smooth endoplasmic reticulum and increases in microsomal enzymes . . . Plus Sign. Click to expand choices. Liver enlargement, proliferation of smooth endoplasmic reticulum and increases in microsomal enzymes are common hepatic responses of rodents to the administration of single polychlorinated compounds, but little is known regarding the combined effects of 2 such compounds. A study was therefore undertaken of a mixture of polychlorinated biphenyls (PCB) (Aroclor 1254) and Mirex in Charles River CD-1 mice. The compounds were administered in the diet at the following levels for 7 days: group I, chow; group II, PCB 500 ppm; group III, Mirex 90 ppm; and group IV, Mirex 90 ppm and PCB 500 ppm. Loss of body weight, increases in liver weight and demethylase activity were recorded in all 3 experimental groups, being most pronounced in group IV. Glucose 6-phosphatase activity was decreased in groups II and III and remained unchanged in group IV. In mice of group IV there were striking structural changes in hepatic lysosomes, with formulation of large myeloid bodies (lysosomes containing cellular debris) and numerous autophagic vacuoles that were PAS-positive and stained for acid phosphatase. These changes were reflected in the elevated activities of both total and sedimentable acid phosphatase. The lysosomes were normal in all other groups. Further changes included loss of glycogen in groups III and IV and hepatic cell necrosis in group IV. The capacity of the combination of toxicants to elicit unique lysosomal responses posed questions regarding the biological interaction between environmental chemicals. (Author abstract by permission) (Abstract No. 135)
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  • 7.
    Technical Report
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    A study of in vivo physiological and biochemical alterations in the livers of laboratory rats (Sprague-Dawley) following mirex exposure

    Author: Abston, PA
    (1977)
    Minus Sign. Click to see only selected choices. PESTAB. Adult male and female rats fed mirex concentrations of 10-200 ppm ad libitum for a period of . . . Plus Sign. Click to expand choices. PESTAB. Adult male and female rats fed mirex concentrations of 10-200 ppm ad libitum for a period of 1-4 weeks showed significant decreases in hepatic levels of lactic dehydrogenase, malic dehydrogenase, sorbitol dehydrogenase, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase relative to control. Decreases in these enzymes were from the soluble fraction of the hepatocyte. Decreases in the hepatic levels of lactic dehydrogenase and glutamic oxaloacetic transaminase in mirex-fed rats were apparently due to induction of new enzyme protein. Changes in liver enzyme levels were not related to changes in serum cortisol levels. Mirex exposure resulted in significant increases in liver weights, total liver protein, and total liver lipid but did not alter the liver water content (percent of wet weight), liver lipid concentration, or liver protein concentration. Significant alterations of the size and relative concentrations of free-pool amino acids in the liver and serum were observed following one week of 50 ppm mirex feeding. At the end of three weeks the size of the liver amino acid pool returned to normal in both male and female rats, although the ratios of the concentrations of the amino acids in the pool were significantly different from the control. Changes in liver and serum amino acids indirectly indicated a potential alteration in hepatic gluconeogenesis following mirex feeding. Mirex feeding resulted in a significant decrease in the average time of survival during a subsequent period of starvation for both male and female rat. (Author abstract by permission, abridged. Copies of the thesis are available from University Microfilms, Order No. 77-11,746.)
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  • 8.
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    THE IN VIVO EFFECT OF MIREX ON SOLUBLE HEPATIC ENZYMES IN THE RAT

    Authors: Abston, PA; Yarbrough, JD
    (1976)
    Abstract: EIS: Epidemiology Information System
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  • 9.
    The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
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    The in vivo effects of dietary mirex on hepatic lactic dehydrogenase and glutamic oxaloacetic transaminase levels of the rat

    Authors: Abston, PA; Yarbrough, JD
    (1974) Journal of Agricultural and Food Chemistry 22:66-68.
    Minus Sign. Click to see only selected choices. PESTAB Adult male and female Sprague�Dawley rats were fed standard laboratory chow, ad libitum containing . . . Plus Sign. Click to expand choices. PESTAB Adult male and female Sprague�Dawley rats were fed standard laboratory chow, ad libitum containing mirex in concentrations of 10, 50, 100, and 200 ppm for 4 weeks. Liver homogenates were analyzed for lactic dehydrogenase and glutamic-oxaloacetic transaminase activity. Male liver LDH levels were reduced approxmiately 50% in the 100 and 200 ppm of mirex exposed animals, as compared to control animals, by 2 weeks of dietary mirex and persisted through the test period. Liver GOT levels showed a steady decrease in activity, exhibiting a 60-65% decrease at the end of the 4-week treatment period. With 10 ppm of dietary mirex, male liver LDH levels showed no significant change during the 4-week period, while liver GOT levels were reduced about 26% at the end of 3 weeks. Female rat liver homogenates exhibited an approximate 24% decrease in LDH levels after 3 weeks of dietary feeding of 100 ppm of mirex, while liver GOT levels were reduced about 35% when compared to control animals at 3 weeks. Female rats fed 50 ppm of mirex showed an approximate 25% reduction of LDH levels and about a 28% decrease in GPT liver levels after 4 weeks of exposure. (Author abstract reprinted by permission of the American Chemical Society)
    Tagged With: 06/2015 Litsearch Results, ToxNet
  • 10.
    The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
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    The In Vivo Effects Of Mirex On Hepatic Lactic Dehydrogenase And Glutamic Oxaloacetic Transaminase Levels Of The Rat

    Authors: Abston, PA; Yarbrough, JD
    (1974)
    Minus Sign. Click to see only selected choices. The in-vivo effects of dietary mirex (2385855) exposure on lactic-dehydrogenase (9001609) (LDH) and . . . Plus Sign. Click to expand choices. The in-vivo effects of dietary mirex (2385855) exposure on lactic-dehydrogenase (9001609) (LDH) and glutamic-oxaloacetic-transaminase (9000979) (GOT) activities were studied in rats. Sprague-Dawley-rats were fed diets containing either 10, 50, 100, or 200 parts per million (ppm) mirex for 30 days. Animals were then sacrificed, livers were removed and homogenized, and the homogenate was centrifuged to obtain the supernatant used for spectrophotometric enzyme assays. Male rats fed 10ppm mirex showed no change in LDH activity; however, rats fed both 100 and 200ppm showed about a 50 percent reduction in LDH activity. This drop appeared between days 7 and 14 of exposure and enzyme activity remained depressed for the remainder of the treatment period. Female rat liver LDH activity appeared much less sensitive to mirex exposure than male LDH activity. A drop in male liver GOT activity at 100ppm and 200ppm mirex appeared during the first 7 days of exposure and reached a 60 to 65 percent reduction at the end of 21 days. Female GOT activity was much less affected than male GOT activity. The authors conclude that tissue enzyme levels may serve as a sensitive index of chronic insecticide exposure.
    Tagged With: 06/2015 Litsearch Results, ToxNet

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