Carbofuran-induced Alterations (in Vivo) in High-energy Phosphates, Creatine Kinase (CK) and CK Isoenzymes

Overview

Journal Arch Toxicol

Specialty Toxicology

Date 1991 Jan 1

PMID 1953349

Citations 4

Authors

R C Gupta

J T Goad

W L Kadel

Affiliations

Soon will be listed here.

Abstract

Male Sprague-Dawley rats administered with an acute sublethal dose of carbofuran (1.5 mg/kg, s.c.) developed the signs of peak hypercholinergic activity during 30-60 min. At this time, in hemidiaphragm muscle, a significant decrease in ATP (28%) and phosphocreatine (PC) (29%) occurred without concurrent change in AMP and creatine (CR). A significant decrease in the levels of total adenine nucleotides (ATP + ADP + AMP) (20%) and total creatine compounds (PC + CR) (17%) was evident. The decline in the corresponding ratios of ATP/ADP (26%), ATP/AMP (39%), and PC/CR (20%) was therefore suggestive of greater utilization of ATP and PC in response to their increased demand for high-frequency muscle fasciculations. The energy charge = ATP + 1/2 ADP/(ATP + ADP + AMP), an index of high-energy phosphate adequacy in hemidiaphragm, remained unchanged. A significant (p less than 0.01) increase in serum magnesium with no concurrent change in calcium was also evident. The observed higher activity (152%) of total CK (EC 2.7.3.2) in the serum induced by carbofuran was possibly a reflection of more than a twofold increase in CK-BB isoenzyme (CK-1) and 141% increase in CK-MM isoenzyme (CK-3), which also strengthens our findings of enhanced synthesis of ATP and PC. Increased levels of CK-MM isoenzyme in the brain (253%) and hemidiaphragm (195%); and depletion of CK-BB isoenzyme in the hemidiaphragm (0%), heart (42%), and brain (77%), and of CK-MB isoenzyme (CK-2) in the brain (4%) and hemidiaphragm (14%), appeared to be the major contributory factors leading to enhanced serum CK activity.

Citing Articles

Mitochondrial oxidative stress and dysfunction in rat brain induced by carbofuran exposure.

Kamboj S, Kumar V, Kamboj A, Sandhir R Cell Mol Neurobiol. 2008; 28(7):961-9.

PMID: 18340526 PMC: 11515469. DOI: 10.1007/s10571-008-9270-5.

Carbofuran-induced oxidative stress in mammalian brain.

Rai D, Sharma B Mol Biotechnol. 2007; 37(1):66-71.

PMID: 17914167 DOI: 10.1007/s12033-007-0046-9.

Perturbed synaptosomal calcium homeostasis and behavioral deficits following carbofuran exposure: neuroprotection by N-acetylcysteine.

Kamboj A, Sandhir R Neurochem Res. 2007; 32(3):507-16.

PMID: 17268844 DOI: 10.1007/s11064-006-9264-y.

Carbofuran-induced neurochemical and neurobehavioral alterations in rats: attenuation by N-acetylcysteine.

Kamboj A, Kiran R, Sandhir R Exp Brain Res. 2005; 170(4):567-75.

PMID: 16307259 DOI: 10.1007/s00221-005-0241-5.

In vivo alterations in lactate dehydrogenase (LDH) and LDH isoenzymes patterns by acute carbofuran intoxication.

Gupta R, Goad J, Kadel W Arch Environ Contam Toxicol. 1991; 21(2):263-9.

PMID: 1958080 DOI: 10.1007/BF01055345.

References

Fitch C, Jellinek M, Mueller E . Experimental depletion of creatine and phosphocreatine from skeletal muscle. J Biol Chem. 1974; 249(4):1060-3. View

Saks V, Chernousova G, Gukovsky D, Smirnov V, Chazov E . Studies of energy transport in heart cells. Mitochondrial isoenzyme of creatine phosphokinase: kinetic properties and regulatory action of Mg2+ ions. Eur J Biochem. 1975; 57(1):273-90. DOI: 10.1111/j.1432-1033.1975.tb02299.x. View

Petrofsky J, Fitch C . Contractile characteristics of skeletal muscles depleted of phosphocreatine. Pflugers Arch. 1980; 384(2):123-9. DOI: 10.1007/BF00584427. View

Gupta R, Patterson G, Dettbarn W . Acute tabun toxicity; biochemical and histochemical consequences in brain and skeletal muscles of rat. Toxicology. 1987; 46(3):329-41. DOI: 10.1016/0300-483x(87)90213-7. View

McLeod Jr C . Pathology of nerve agents: perspectives on medical management. Fundam Appl Toxicol. 1985; 5(6 Pt 2):S10-6. DOI: 10.1016/0272-0590(85)90110-1. View

Gupta R, Misulis K, Dettbarn W . Activity dependent characteristics of fast and slow muscle: biochemical and histochemical considerations. Neurochem Res. 1989; 14(7):647-55. DOI: 10.1007/BF00964874. View

Petras J . Soman neurotoxicity. Fundam Appl Toxicol. 1981; 1(2):242. DOI: 10.1016/s0272-0590(81)80065-6. View

Gupta R, Dettbarn W . Alterations of high-energy phosphate compounds in the skeletal muscles of rats intoxicated with diisopropylphosphorofluoridate (DFP) and Soman. Fundam Appl Toxicol. 1987; 8(3):400-7. DOI: 10.1016/0272-0590(87)90089-3. View

Gupta R, Patterson G, Dettbarn W . Biochemical and histochemical alterations following acute soman intoxication in the rat. Toxicol Appl Pharmacol. 1987; 87(3):393-402. DOI: 10.1016/0041-008x(87)90244-4. View

10.

SERAYDARIAN M, ABBOTT B, WILLIAMS E . Studies on the frog's sartorius at different stages of activity. Biochim Biophys Acta. 1961; 46:355-63. DOI: 10.1016/0006-3002(61)90759-4. View

11.

Hull-Ryde E, Cummings R, Lowe J . Improved method for high energy nucleotide analysis of canine cardiac muscle using reversed-phase high-performance liquid chromatography. J Chromatogr. 1983; 275(2):411-7. DOI: 10.1016/s0378-4347(00)84388-1. View

12.

Gupta R, Kadel W . Prevention and antagonism of acute carbofuran intoxication by memantine and atropine. J Toxicol Environ Health. 1989; 28(1):111-22. DOI: 10.1080/15287398909531332. View

13.

Lemercier G, Carpentier P, Sentenac-Roumanou H, MORELIS P . Histological and histochemical changes in the central nervous system of the rat poisoned by an irreversible anticholinesterase organophosphorus compound. Acta Neuropathol. 1983; 61(2):123-9. DOI: 10.1007/BF00697391. View

14.

Saks V, Rosenshtraukh L, Smirnov V, Chazov E . Role of creatine phosphokinase in cellular function and metabolism. Can J Physiol Pharmacol. 1978; 56(5):691-706. DOI: 10.1139/y78-113. View

15.

Weber A, Murray J . Molecular control mechanisms in muscle contraction. Physiol Rev. 1973; 53(3):612-73. DOI: 10.1152/physrev.1973.53.3.612. View

16.

Cisson C, Wilson B . Degenerative changes in skeletal muscle of hens with tri-ortho-cresyl phosphate-induced delayed neurotoxicity: altered acetylcholinesterase molecular forms and increased plasma creatine phosphokinase activity. Toxicol Appl Pharmacol. 1982; 64(2):289-305. DOI: 10.1016/0041-008x(82)90224-1. View

17.

Gupta R, Patterson G, Dettbarn W . Mechanisms of toxicity and tolerance to diisopropylphosphorofluoridate at the neuromuscular junction of the rat. Toxicol Appl Pharmacol. 1986; 84(3):541-50. DOI: 10.1016/0041-008x(86)90259-0. View

18.

CAIN D, Davies R . Breakdown of adenosine triphosphate during a single contraction of working muscle. Biochem Biophys Res Commun. 1962; 8:361-6. DOI: 10.1016/0006-291x(62)90008-6. View

19.

Gupta R, Kadel W . Toxic interaction of tetraisopropylpyrophosphoramide and propoxur: some insights into the mechanisms. Arch Environ Contam Toxicol. 1990; 19(6):917-20. DOI: 10.1007/BF01055061. View

20.

Gupta R, Patterson G, Dettbarn W . Comparison of cholinergic and neuromuscular toxicity following acute exposure to sarin and VX in rat. Fundam Appl Toxicol. 1991; 16(3):449-58. DOI: 10.1016/0272-0590(91)90085-i. View