Biochemical, oxidative and histological changes caused by sub-acute oral exposure of some synthetic cyanogens in rats: Ameliorative effect of α-ketoglutarate

Food and Chemical Toxicology

Volumn 67, Issue , 2014, Pages 201-211

  Bhattacharya, Rahul ^a   Rao, Pooja ^a   Singh, Poonam ^a   Yadav, Shiv Kumar ^a   Upadhyay, Preeti ^a,b   Malla, Sandhya ^a,c   Gujar, Niranjan Laxman ^a   Lomash, Vinay ^a   Pant, Satish Chandra ^a  

^a DEFENCE RESEARCH AND DEVELOPMENT ESTABLISHMENT   (India)

^b Sant Hirdaram Girls College   (India)

^c BOSTON COLLEGE   (United States)

Author keywords

Ketoglutarate; Cyanogens; Oxidative damage; Protection; Sub acute toxicity

Indexed keywords

2 OXOGLUTARIC ACID; ALANINE AMINOTRANSFERASE; ANTIOXIDANT; ASPARTATE AMINOTRANSFERASE; CATALASE; CYANIDE; CYTOCHROME C OXIDASE; GLUCOSE; GLUTATHIONE; GLUTATHIONE PEROXIDASE; GLUTATHIONE REDUCTASE; LACTATE DEHYDROGENASE; MALONALDEHYDE; MALONONITRILE; NITROPRUSSIDE SODIUM; PROPIONITRILE; SUPEROXIDE DISMUTASE; THIOCYANATE; THIOSULFATE SULFURTRANSFERASE; ALPHA-KETOGLUTARIC ACID; CYANOGEN; NITRILE;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIOXIDANT ACTIVITY; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BRAIN HOMOGENATE; BRAIN LEVEL; CONTROLLED STUDY; CYANIDE POISONING; ENZYME INHIBITION; FEMALE; GLUCOSE BLOOD LEVEL; HISTOPATHOLOGY; KIDNEY LEVEL; LACTATE DEHYDROGENASE BLOOD LEVEL; LEUKOCYTE COUNT; LIVER HOMOGENATE; LIVER LEVEL; LONG TERM EXPOSURE; NONHUMAN; OXIDATIVE STRESS; RAT; THROMBOCYTE COUNT; TISSUE LEVEL; ANIMAL; ORAL DRUG ADMINISTRATION; TOXICITY; WISTAR RAT;

ADMINISTRATION, ORAL; ANIMALS; FEMALE; KETOGLUTARIC ACIDS; NITRILES; RATS; RATS, WISTAR;

EID: 84897865364     PISSN: 02786915     EISSN: 18736351     Source Type: Journal    
DOI: 10.1016/j.fct.2014.02.038     Document Type: Article

References (66)

1. Ahmad S., White C.W., Chang L., Schneider B.K., Allen C.B. Glutamine protects mitochondrial structure and function in oxygen toxicity. Am. J. Physiol. Lung Cell Mol. Physiol. 2001, 280:779-791.
2. Andrae U., Singh J., Zeigler-Skylakakis K. Pyruvate and related alpha-ketoacids protect mammalian cells in culture against hydrogen peroxide-induced cytotoxicity. Toxicol. Lett. 1985, 28:93-98.
3. Ardelt B.K., Borowitz J.L., Isom G.E. Brain lipid peroxidation and antioxidant protectant mechanisms following acute cyanide intoxication. Toxicology 1989, 56:147-154.
4. Ardelt B.K., Borowitz J.L., Maduh E.U., Swain S.L., Isom G.E. Cyanide-induced lipid peroxidation in different organs. Subcellular distribution and hydroperoxide generation in neuronal cells. Toxicology 1994, 89:127-137.
5. Aussel C., Coudray-Lucas C., Lasnier E., Cynober L., Ekindjian O.G. α-Ketoglutarate uptake in human fibroblasts. Cell Biol. Intern. 1996, 20:359-363.
6. Ballantyne B. Toxicology of cyanides. Clinical and Experimental Toxicology of Cyanides 1987, 98-114. IOP Publishing Ltd., Bristol, England. B. Ballantyne, T.C. Marrs (Eds.).
7. Baskin S.I., Kelly J.B., Maliner B.I., Rockwood G.A., Zoltani C. Cyanide poisoning. Medical Aspects of Chemical Warfare 2008, 372-410. TMM Publications, Washington. S. Tuorinsky (Ed.).
8. Bhattacharya R. α-Ketoglutarate: a promising antidote to cyanide poisoning. Pharmacological Perspectives of Toxic Chemicals and their Antidotes 2004, 411-430. Narosa Publishing House, New Delhi, India. S.J.S. Flora, J.A. Romano, S.I. Baskin, K. Sekhar (Eds.).
9. Bhattacharya R., Flora S.J.S. Cyanide toxicity and its treatment. Handbook of Toxicology of Chemical Warfare Agents 2009, 255-270. Elsevier, New York. R.C. Gupta (Ed.).
10. Bhattacharya R., Vijayraghavan R. Promising role of alpha-ketoglutarate in protecting against the lethal effects of cyanide. Hum. Exp. Toxicol. 2002, 21:297-303.
11. Bhattacharya R., Rao P.V.L., Vijayaraghavan R. In vitro and in vivo attenuation of experimental cyanide poisoning by α-ketoglutarate. Toxicol. Lett. 2002, 128:185-195.
12. Bhattacharya R., Satpute R.M., Hariharakrishnan J., Tripathi H., Saxena P.B. Acute toxicity of some synthetic cyanogens in rats and their response to oral treatment with alpha-ketoglutarate. Food Chem. Toxicol. 2009, 47:2314-2320.
13. Bismuth C., Baud F.J., Djeghout H., Astier A., Aubriot D. Cyanide poisoning from propionitrile exposure. J. Emerg. Med. 1987, 5:191-195.
14. Bowler R.G. The determination of thiocyanate in blood serum. Biochem. J. 1944, 38:385-388.
15. Broderick K.E., Balasubramanian M., Chan A., Potluri P., Feala J., Belke D.D., McCulloch A., Sharma V.S., Pilz R.B., Bigby T.D., Boss G.R. The cobalamin precursor cobinamide detoxifies nitroprusside-generated cyanide. Exp. Biol. Med. 2007, 232:789-798.
16. Buddington R.K., Pajor A., Buddington K.K., Pierzynowski S. Absorption of alpha-ketoglutarate by the gastrointestinal tract of pigs. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 2004, 132:215-220.
17. Chanas B., Wang H., Ghanayem B.I. Differential metabolism of acrylonitrile to cyanide is responsible for the greater sensitivity of male vs. female mice. Role of CYP2E1 and epoxide hydrolases. Toxicol. Appl. Pharmacol. 2003, 193:293-302.
18. Cole P.V., Vessey C.J. Sodium thiosulfate decreases blood cyanide concentration following sodium nitroprusside. Br. J. Anaes. 1988, 60:745-746.
19. Conn A.R., Steele R.D. Transport of alpha-keto analogues of amino acids across blood-brain barrier in rats. Am. J. Physiol. 1982, 243:E272-E277.
20. Cooper A.J.L., Ginos J.Z., Meister A. Synthesis and properties of the alpha-keto acids. Chem. Rev. 1983, 83:321-358.
21. Cooperstein S.J., Lazarow A. A microspectrophotometric method for the determination of cytochrome oxidase. J. Biol. Chem. 1951, 189:665-670.
22. Cynober L. Ornithine α-ketoglutarate in nutritional support. Nutrition 1991, 7:313-322.
23. Daya S., Walker R.B., Dukie S.K. Cyanide-induced free radical production in rat brain homogenate is reduced by aspirin. Metab. Brain Dis. 2000, 5(3):203-210.
24. 2S cytotoxicity mechanism involves reactive oxygen species formation and mitochondrial depolarization. Toxicol. Lett. 2004, 203:69-76.
25. Elliott W.J. Clinical features and management of selected hypertensive emergencies. J. Clin. Hypertens. 2004, 6:S87-S92.
26. Elsaid F.G., Elkomy M.M. Aqueous garlic extract and sodium thiosulphate as antidotes for cyanide intoxication in albino rats. Res. J. Med. Med. Sci. 2006, 1(2):50-56.
27. Enongene E.N., Sun P.N., Mehta C.S. Sodium thiosulfate protects against acrylonitrile-induced elevation of glial fibrillary acidic protein levels by replenishing glutathione. Environ. Toxicol. Pharmacol. 2000, 8:153-161.
28. Epstein J. Estimation of microqunatities of cyanide. Anal. Chem. 1947, 19:272-274.
29. Farooqui M.Y.H., Ahmed A.E. Molecular interaction of acrylonitrile and potassium cyanide with rat blood. Chem. Biol. Interact. 1982, 38:145-159.
30. Feldstein M., Klendshoj N.C. The determination of cyanide in biologic fluids by microdiffusion analysis. J. Lab. Clin. Med. 1954, 44:166-170.
31. Hadri L.El., Chanas B., Ghanayem B.I. Comparative metabolism of methacrylonitrile and acrylonitrile to cyanide using cytochrome p4502E1 and microsomal epoxide hydrolase-null mice. Toxicol. Appl. Pharmacol. 2005, 205:116-125.
32. Hariharakrishnan J., Anand T., Satpute R.M., Jayaraj R., Prasad G.B.K.S., Bhattacharya R. Activity and gene expression profile of certain antioxidant enzymes in different organs of rats after subacute cyanide exposure: effect of alpha-ketoglutarate. Drug Chem. Toxicol. 2009, 32(3):268-276.
33. Hissin P.J., Hilf R. A fluorimetric method for determination of oxidised and reduced glutathione in tissue. Anal. Biochem. 1976, 74:214-226.
34. HSDB (Hazardous Substances Data Bank). 2003. Propionitrile. Reviewed 3/17/03. U.S. National Library of Medicine, Natl. Inst. Health, Dept. of Health and Human Services, Bethesda, MD.
35. Lockwood A., Patka J., Rabinovich M., Wyatt K., Abraham P. Sodium nitroprusside-associated cyanide toxicity in adult patients - fact or fiction? A critical review of the evidence and clinical relevance. Open Access J. Clin. Trials 2010, 2:133-148.
36. Mathangi D.C., Shyamala R., Vijayashree R., Rao K.R., Ruckmani A., Vijayraghavan R., Bhattacharya R. Effect of alpha-ketoglutarate on neurobehavioral, neurochemical and oxidative changes caused by sub-chronic cyanide poisoning in rats. Neurochem. Res. 2011, 36:540-548.
37. Mc Manus J.F.A., Mowry R.W. General methods for study of cell and its structure. Staining Methods: Histologic and Histochemical 1965, 73-90. Harper Bros, New York. J.F.A. Mc Manus, R.W. Mowry (Eds.).
38. NAC (National Advisory Committee on Acute Exposure Guideline Levels (AEGL) for selected aliphatic nitriles, 2007. Interim report. <> (downloaded 13.09.13). http://www.epa.gov/opptintr/aegl/pubs/aliphaticnitriles_tsd_interimversion_1_07_2007.pdf.
39. Nagahara N., Ito T., Kitamura H., Nishino T. Tissue distribution of mercaptopyruvate sulfurtransferases in the rat: confocal laser fluorescence and immunoelectron microscopic studies combined with biochemical analysis. Histochem. Cell Biol. 1998, 110:243-250.
40. Nath A.K., Roberts L.D., Liu Y., Mahon S.B., Kim S., Ryu J.H., Werdich A., Januzzi J.L., Boss G.R., Rockwood G.A., MacRae C.A., Brenner M., Gerszten R.E., Peterson R.T. Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure. FASEB J. 2013, 27:1928-1938.
41. Norris J.C., Uteley W.A., Hume A.S. Mechanism of antagonizing cyanide induced lethality by α-ketoglutaric acid. Toxicology 1990, 64:275-283.
42. Okhawa H., Ohishi W., Yogi K. Assay formulation lipid peroxidase in animal tissue by thiobarbituric acid reaction. Anal. Biochem. 1979, 95:51.
43. Okolie N.P., Osagie A.U. Liver and kidney lesions and associated enzyme changes induced in rabbits by chronic cyanide exposure. Food Chem. Toxicol. 1999, 37:745-750.
44. Pangborn J.B., Hicks J.T., Chambers J.R., Shahani K.M. A Monograph on alpha-Ketoglutaric Acid 1990, Bionostics Inc., Lisle, Illinois, USA.
45. Patnaik P. A Comprehensive Guide to the Hazardous Properties of Chemical Substances 2007, John Wiley & Sons Inc., NJ, USA. third ed.
46. Pozo A.L., Godfrey E.M., Bowles K.M. Splenomegaly: investigation, diagnosis and management. Blood Rev. 2009, 23:105-111.
47. Rao P., Singh P., Yadav S.K., Gujar N.L., Bhattacharya R. Acute toxicity of some synthetic cyanogens in rats: time-dependent cyanide generation and cytochrome oxidase inhibition in soft tissues after sub-lethal oral intoxication. Food Chem. Toxicol. 2013, 59:595-609.
48. Rehncrona S., Folbergrova J., Smith D.S., Siesjo B.K. Influence of complete and pronounced cerebral ischemia and subsequent recirculation on cortical concentrations of oxidized and reduced glutathione in rat. J. Neurochem. 1980, 34:477-486.
49. Rongzhu L., Ziqiang C., Fusheng J., Collins J.J. Neurobehavioral effects of occupational exposure to acrylonitrile in Chinese workers. Environ. Toxicol. Pharmacol. 2005, 19:695-700.
50. Rouisse L., Chakrabati S., Tuchweber B. Nephrotoxic potential of acrylonitrile in Fisher 344 rats. Toxicologist 1986, 6:180.
51. Saillenfait A.M., Sabate J.P. Comparative developmental toxicities of aliphatic nitriles: in vivo and in vitro observations. Toxicol. Appl. Pharmacol. 2000, 163:149-163.
52. Satpute R.M., Hariharakrishnan J., Lomash V., Gujar N.L., Rao P., Singh P., Bhattacharya R. Oxidative stress and tissue pathology caused by sub-acute ammonium acetate exposure in rats and their response to treatments of alpha-ketoglutarate and N-acetyl cysteine. Toxicol. Ind. Health 2014, 30:12-24.
53. Scolnick B., Hamel D., Woolf A.D. Successful treatment of life threatening propionitrile exposure with sodium thiosulfate followed by hyperbaric oxygen. J. Occup. Med. 1993, 35:577-580.
54. Singh P., Rao P., Bhattacharya R. Dose and time-dependent effects of cyanide on thiosulfate sulfurtransferases and cystathionine-λ-lyase activities. J. Biochem. Mol. Toxicol. 2013, 27:499-507.
55. Sipe E.K., Trienski T.L., Porter J.M. Cyanide toxicity in the surgical intensive care unit: a case report. Am. Surg. 2001, 67:684-686.
56. Sousa A.B., Soto-Blanco B.J., Guerra L., Kimura E.T., Gorniak S.L. Does prolonged oral exposure to cyanide promote hepatotoxicity and nephrotoxicity?. Toxicology 2002, 174:87-95.
57. Stipanuk M.H., Ueki L. Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur. J. Inherit. Metab. Dis. 2011, 34:17-32.
58. Sylvester M., Sander C. Immunohistochemical localization of rhodanese. Histochem. J. 1990, 22:197-200.
59. Tulsawani R.K., Bhattacharya R. Effect of α-ketoglutarate on cyanide-induced biochemical alterations in rat brain and liver. Biomed. Environ. Sci. 2006, 19:61-66.
60. Tulsawani R.K., Debnath M., Pant S.C., Kumar O., Prakash A.O., Vijayaraghavan R., Bhattacharya R. Effects of sub-acute oral cyanide administration in rats: protective efficacy of alpha-ketoglutarate and sodium thiosulfate. Chem. Biol. Interact. 2005, 156:1-12.
61. Varma S.D., Hegde K.R. The effect of alpha ketoglutarate against selenite cataract formation. Exp. Eye Res. 2004, 79:913-918.
62. Vaughan C.J., Delanty N. Hypertensive emergencies. Lancet 2000, 356:411-417.
63. Velvizhi S., Nagalashmi T., Essa M.M., Dakshayani K.B., Subramanian P. Effects of α-ketoglutarate on lipid peroxidation status during chronic ethanol administration in Wistar rats. Pol. J. Pharmacol. 2002, 54:231-236.
64. Vesey C.J., Cole P.V. Blood cyanide and thiocyanate concentrations produced by long-term therapy with sodium nitroprusside. Br. J. Anaes. 1985, 57:148-155.
65. Westley J. Thiosulphate: cyanide sulfurtransferase (Rhodanese). Meth. Enzymol. 1981, 77:285-290.
66. Wu Jong-C., Hseu You C., Chen Chin-H., Wang Shu-H., Chen Ssu C. Comparative investigations of genotoxic activity of five nitriles in the comet assay and the Ames test. J. Hazard. Mater. 2009, 169:492-497.