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Alterations in free radical scavenger system profile of type I diabetic rat brain

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Molecular and Chemical Neuropathology

Abstract

The activities of the enzymes related to glutathione synthesis, degradation, and functions as well as reactive oxygen scavenging enzymes were analyzed in different brain regions, such as cerebral hemisphere, cerebellum, brainstem, thalamus, and hypothalamus after 1 and 3 mo of streptozotocin-induced diabetes in rats. Parallel studies were also made in age-matched control rats and insulin-treated diabetic rats. The content of glutathione (GSH) and its synthesizing enzyme γ-glutamylcystein synthetase and also superoxide dismutase (SOD) and catalase activities (reactive oxygen scavenging enzymes) were significantly decreased from almost all the brain regions studied. However, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), γ-glutamyl transpeptidase (γ-GTP), and glutamine synthetase (GS) activities were increased in the diabetic rat brain. Insulin treatment to the diabetic rats resulted in partial to full recovery in these enzymes activities. The present results emphasize the potentially serious alterations of brain free radical scavenger system in uncontrolled Type I diabetes.

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References

  • Aebi H. (1984) Catalase in vitro.Methods Enzymol. 105, 121–126.

    PubMed  CAS  Google Scholar 

  • Bhardwaj S. K., Sharma M. L., Gulati G., Chhabra A., Kaushik R., Sharma P., et al. (1998) Effect of starvation and insulin induced hypoglycemia on oxidative stress scavenger system and electron transport chain complexes from rat brain, liver and kidney.Mol. Chem. Neuropathol., this issue.

  • Bray R. C., Cockle S. A., Fielden E. M., Roberts P. B., Rotilio G., and Calabrese L. (1974) Reduction and inactivation of superoxide dismutase by hydrogen peroxide.Biochem. J. 139, 43–48.

    PubMed  CAS  Google Scholar 

  • Carlberg I. and Mannervik B. (1975) Purification and characterization of flavo enzyme glutathione reductase from rat liver.J. Biol. Chem. 250, 5475–5480.

    PubMed  CAS  Google Scholar 

  • Cooper A. J. L. and Meister A. (1993) Glutathione in the brain. Disorders of glutathione metabolism, inThe Molecular and Genetic Basis of Neurological Disease (Rosenberg R., Prusiner S., DiMauro S., Barchi R., and Kunkel L., eds.), pp. 209–238, Butterworth-Heinemann, Boston.

    Google Scholar 

  • Di Simplicio P., de Giorgio L. A., Cardaioli E., Lecis R., Miceli M., Rossi R., et al. (1995) Glutathione, glutathione utilizing enzymes and thiotransferase in platelets of insulin dependent diabetic patients: Relation with platelet aggregation and with microangiopatic complications.Eur. J. Clin. Invest. 25, 665–669.

    Article  PubMed  Google Scholar 

  • Flohe L. and Gunzler W. A. (1984) Assyas of glutathione peroxidase.Methods Enzymol. 105, 114–121.

    PubMed  CAS  Google Scholar 

  • Griffith O. W. and Meister A. (1985) Origin and turnover of mitochondrial glutathione.Proc. Natl. Acad. Sci. USA 82, 4668–4672.

    Article  PubMed  CAS  Google Scholar 

  • Gsell W., Conrad R., Hickethier M., Sotic E., Frolich L., Wichart I., et al. (1995) Decreased catalase activity but unchanged superoxide dismutase activity in brains of patients with dementia of Alzheimer type.J. Neurochem. 64, 1216–1223.

    Article  PubMed  CAS  Google Scholar 

  • Gutteridge J. M., Quinlan G. J., Clark I., and Halliwell B. (1985) Aluminum salts accelerate peroxidation of membrane lipids stimulated by iron salts.Biochim. Biophys. Acta. 835, 441–447.

    PubMed  CAS  Google Scholar 

  • Habig W. H., Pabst M. J., and Jakoby W. B. (1974) Glutathione S-transferases: The first enzymatic step in mercapturic acid formation.J. Biol. Chem. 249, 7130–7139.

    PubMed  CAS  Google Scholar 

  • Hodgson E. K. and Fridovich I. (1975) The interaction of bovine superoxide dismutase with hydrogen peroxide: Inactivation of the enzymes.Biochemistry 14, 5294–5299.

    Article  PubMed  CAS  Google Scholar 

  • Ip S. P., Poon M. K. T., Wu S. S., Che C. T., Ng K. H., Kong Y. C., et al. (1995) Effect of schisandrin B on hepatic glutathione antioxidant system in mice protection against carbon tetrachloride toxicity.Planta Med. 61, 398–401.

    Article  PubMed  CAS  Google Scholar 

  • Jewett S. L., Cushing S., Gillespie F., Smith D., and Sparks S. (1989) Reaction of bovine liver copper-zinc superoxide dismutase with hydrogen peroxide. Evidence for reaction with H2O2 and H2O leading to loss of copper.Eur. J. Biochem. 180, 569–575.

    Article  PubMed  CAS  Google Scholar 

  • Kakkar R., Kalra J., Mantha S. V., and Prasad K. (1995) Lipid peroxidation and activity of antioxidant enzymes in diabetic rats.Mol. Cell. Biochem. 151, 113–119.

    Article  PubMed  CAS  Google Scholar 

  • Kaur G., Sharma P., Bhardwaj S. K., and Kaur G. (1997) GABA agonists and neurotransmitters metabolizing enzymes in steroid primed OVX rats.Mol. Cell. Biochem. 167, 107–111.

    Article  PubMed  CAS  Google Scholar 

  • Kono Y. (1978) Generation of superoxide radical during autoxidation hydroxylamine and an assay of superoxide dismutase.Arch. Biochem. Biophys. 186, 189–195.

    Article  PubMed  CAS  Google Scholar 

  • Lakhman S. S. and Kaur G. (1997) Effect of experimental diabetes on monoamine oxidase activity from discrete areas of rat brain: Relationship with diabetes associated reproductive failure.Mol. Cell. Biochem. 177, 15–20.

    Article  PubMed  CAS  Google Scholar 

  • Lowry O. H., Rosebrough N. J., Farr A. L., and Randall R. J. (1951) Protein measurement with Folin phenol reagent.J. Biol. Chem. 193, 265–275.

    PubMed  CAS  Google Scholar 

  • Mak D. H., Ip S. P., Li P. C., Poon M. K., and Ko K. M. (1996) Alterations in tissue glutathione antioxidant system in streptozotocin induced diabetic rats.Mol. Cell. Biochem. 162, 153–158.

    Article  PubMed  CAS  Google Scholar 

  • Makar T. K., Hungund B. L., Cook G. A., Kashfi K., and Cooper A. J. L. (1995a) Lipid metabolism and membrane composition are altered in the brains of type-II diabetic mice.J. Neurochem. 64, 2159–2168.

    Article  PubMed  CAS  Google Scholar 

  • Makar T. K., Rimple-Lamhaoura K., Abraham D. G., Gokhale V. S., and Cooper A. J. L. (1995b) Antioxidant defense systems in the brains of type-I diabetic mice.J. Neurochem. 65, 287–291.

    PubMed  CAS  Google Scholar 

  • Meister A. (1983) Selective modification of glutathione metabolism.Science 220, 472–477.

    Article  PubMed  CAS  Google Scholar 

  • Meister A. (1988) Glutathione metabolism and its selective modification.J. Biol. Chem. 263, 17,205–17,208.

    CAS  Google Scholar 

  • Mooradian A. D. (1988) Diabetic complications of central nervous system.Endocr. Rev. 9, 346–356.

    PubMed  CAS  Google Scholar 

  • Mooradian A. D. (1997) Central nervous system complications of diabetes mellitus—a perspective from the blood brain barrier.Brain Res. Rev. 23, 210–218.

    Article  PubMed  CAS  Google Scholar 

  • Naftalin L., Sexton M., Whitaker J. F., and Tracey D. (1969) A routine procedure for estimating serum γ-glutamyl-transpeptidase activity.Clin. Chim. Acta 26, 293–296.

    Article  PubMed  CAS  Google Scholar 

  • Pamilijans V., Krishnaswamy P. R., Dumville G., and Meister A. (1962) Studies on the mechanism of glutamine synthetase: Isolation and properties of the enzymes from sheep brain.Biochemistry 1, 153–158.

    Article  Google Scholar 

  • Petito C. K., Chung M. C., Verkhovsky L. M., and Cooper A. J. L. (1992) Brain glutamine synthetase increases following cerebral ischemia in the rat.Brain Res. 569, 275–280.

    Article  PubMed  CAS  Google Scholar 

  • Richman P. and Meister A. (1975) Regulation of γ-glutamylcysteine synthetase.J. Biol. Chem. 265, 1588–1593.

    Google Scholar 

  • Sedlak J. and Lindsay R. H. (1968) Estimation of total, protein bound and non protein sulfhydryl groups in tissue with Ellman’s reagent.Anal. Biochem. 25, 192–205.

    Article  PubMed  CAS  Google Scholar 

  • Seelig G. F. and Meister A. (1985) Glutathione biosynthesis: γ-glutamylcysteine synthetase from rat kidney.Methods Enzymol. 113, 379–382.

    PubMed  CAS  Google Scholar 

  • Slivka A., Mytilineou C., and Cohen G. (1987) Histochemical evaluation of glutathione in brain.Brain Res. 409, 275–284.

    Article  PubMed  CAS  Google Scholar 

  • Tayarani I., Chaudiere J., Lefauconnier J. M., and Bourre J. M. (1987) Enzymatic protection against peroxidative damage in isolated brain capillaries.J. Neurochem. 48, 1399–1402.

    Article  PubMed  CAS  Google Scholar 

  • Toleikis P. M. and Godin D. V. (1995) Alteration of antioxidant status in diabetic rats by chronic exposure to psychological stressor.Pharmacol. Biochem. Behav. 52, 355–366.

    Article  PubMed  CAS  Google Scholar 

  • Ulig S. and Wendel A. (1992) The physiological consequences of glutathione variations.Life Sci. 51, 1083–1094.

    Article  Google Scholar 

  • Vasudevan P. T. and Weiland R. H. (1990) Deactivation of catalase by hydrogen peroxide.Biotechnol. Bioeng. 36, 783–789.

    Article  CAS  PubMed  Google Scholar 

  • Ward J. D. (1992) Diabetic neuropathy, inInternational Text Book of Diabetes Mellitus (Alberti K. G. M. M., DeFronzo R. A., Keen H., and Zimmet P. eds.), pp. 1385–1417, Wiley, New York.

    Google Scholar 

  • Yoshida K., Hirokawa J., Tagami S., Kawakami Y., Urata Y., and Kondo T. (1995) Weakened cellular scavenging activity against oxidative stress in diabetes mellitus: Regulation of glutathione synthesis and efflux.Diabetologia 38, 201–210.

    Article  PubMed  CAS  Google Scholar 

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Bhardwaj, S.K., Sharma, P. & Kaur, G. Alterations in free radical scavenger system profile of type I diabetic rat brain. Molecular and Chemical Neuropathology 35, 187–202 (1998). https://doi.org/10.1007/BF02815124

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