Toxicological Updates
Influence of lead acetate on glutathione and its related enzymes in different regions of rat brain
Kiran Kumar Bokara,
Iesha Blaylock,
Stacy Brown Denise,
Rajanna Bettaiya,
Sharada Rajanna,
Prabhakara Rao Yallapragada,
Kiran Kumar Bokara
Division of Animal Physiology and Toxicology, Department of Zoology, Andhra University, Visakhapatnam 530 003, India.
Search for more papers by this authorIesha Blaylock
Department of Biological Sciences, Alcorn State University, Lorman, MS 39096, USA
Search for more papers by this authorStacy Brown Denise
Department of Biological Sciences, Alcorn State University, Lorman, MS 39096, USA
Search for more papers by this authorRajanna Bettaiya
Department of Biological Sciences, Alcorn State University, Lorman, MS 39096, USA
Search for more papers by this authorSharada Rajanna
Department of Biological Sciences, Alcorn State University, Lorman, MS 39096, USA
Search for more papers by this authorCorresponding Author
Prabhakara Rao Yallapragada
Division of Animal Physiology and Toxicology, Department of Zoology, Andhra University, Visakhapatnam 530 003, India.
Division of Animal Physiology and Toxicology, Department of Zoology, Andhra University, Visakhapatnam 530 003, India.Search for more papers by this author
Kiran Kumar Bokara,
Iesha Blaylock,
Stacy Brown Denise,
Rajanna Bettaiya,
Sharada Rajanna,
Prabhakara Rao Yallapragada,
Kiran Kumar Bokara
Division of Animal Physiology and Toxicology, Department of Zoology, Andhra University, Visakhapatnam 530 003, India.
Search for more papers by this authorIesha Blaylock
Department of Biological Sciences, Alcorn State University, Lorman, MS 39096, USA
Search for more papers by this authorStacy Brown Denise
Department of Biological Sciences, Alcorn State University, Lorman, MS 39096, USA
Search for more papers by this authorRajanna Bettaiya
Department of Biological Sciences, Alcorn State University, Lorman, MS 39096, USA
Search for more papers by this authorSharada Rajanna
Department of Biological Sciences, Alcorn State University, Lorman, MS 39096, USA
Search for more papers by this authorCorresponding Author
Prabhakara Rao Yallapragada
Division of Animal Physiology and Toxicology, Department of Zoology, Andhra University, Visakhapatnam 530 003, India.
Division of Animal Physiology and Toxicology, Department of Zoology, Andhra University, Visakhapatnam 530 003, India.Search for more papers by this authorAbstract
This study is intended to determine the effect of lead acetate on glutathione and its associated enzymes of rat brain. Wistar male rats were treated with lead acetate (500 ppm) through drinking water for a period of 8 weeks and parallel controls were maintained. They were sacrificed at the first, fourth and eighth week to isolate whole brains, which were separated into cerebellum, hippocampus, frontal cortex and brain stem. The data indicate enhanced (P < 0.05) glutathione peroxidase (G-Px) activity at most of the intervals for cerebellum, frontal cortex and brain stem, suggesting conversion of GSH to GSSG, while the hippocampus showed decreased levels. In contrast, glutathione reductase (GR) decreased significantly (P < 0.05) in cerebellum, frontal cortex and brain stem at all intervals except the fourth week in frontal cortex and brain stem. Hippocampus exhibited a gradual and significant (P < 0.05) increase in GR activity. Glutathione-S-transferase (GSTase) activity increased with exposure time in all four brain tissues, showing protection against lead acetate toxicity. The GSH and GSSG levels correlated well with the activities of GPx, GR and GSTase in all four regions of the brain. Overall the results indicate that lead acetate affects glutathione-related enzymes differentially and these changes can be attributed to differences in tissue susceptibility. Copyright © 2009 John Wiley & Sons, Ltd.
References
- Adonaylo VN, Oteiza PI. 1999. Lead intoxication: antioxidant defenses and oxidative damage in rat brain. Toxicology. 135: 77–85.
- Altmann L, Weinberg F, Sveinsson K, Lileinthal H, Wiegand H, Winneke G. 1993. Impairment of long term potentiation following chronic lead exposure. Toxicol. Lett. 66: 105–112.
- Basha MR, Wei W, Brydie M. Razmiafshari M, Zawia NH. 2003. Lead-induced developmental perturbations in hippocampal Sp1 DNA-binding are prevented by zinc supplementation: In vivo evidence for Pb and Zn competition. Int. J. Dev. Neurosci. 21: 1–12.
- Beiswanger CM, Diegmann MH, Novak RF, Philbert MA, Graessle TL, Reuhl KR, Lowndes HE. 1995. Developmental changes in the cellular distribution of glutathione and glutathione S-transferases in the murine nervous system. Neurotoxicol. 16: 425–440.
- Bellinger DC. 2007. Lead neurotoxicity in children: decomposing the variability in dose–effect relationships. Am. J. Ind. Med. 50: 720–728.
- Bennet C, Rajanna B, Sharada R, Baker L, Yallapragada PR, Brice JJ, White SL, Kiran Kumar B. 2007. Region specific increase in the antioxidant enzymes and lipid peroxidation products in the brain of rats exposed to lead. Free. Radic. Res. 41: 267–273.
- Canfield RL, Henderson CRJ, Cory-Slechta DA, Cox C, Jusko TA, Lanphear BP. 2003. Intellectual impairment in children with blood lead concentrations below 10 µg per deciliter. New Engl. J. Med. 348: 1517–1526.
- Carlberg I, Mannervik B. 1985. Glutathione reductase. Meth. Enzymol. 113: 484–499.
- Chen SM, Swilley S, Bell R, Rajanna S, Reddy SLN, Rajanna B. 2000. Lead-induced alterations in nitrite and nitrate levels in different regions of the rat brain. Comp. Biochem. Physiol. 125: 115–123.
- Dairam A, Limson JL, Watkins GM, Antunes E, Daya S. 2007. Curcuminoids, curcumin, and demethoxycurcumin reduce lead-induced memory deficits in male Wistar rats. J. Agric. Food. Chem. 55: 1039–1044.
- Dipti P, Yogesh B, Kain AK, Pauline T, Anju B, Sairam M, Singh B, Mongia SS, Kumar GI, Selvamurthy W. 2003. Lead-induced oxidative stress: beneficial effects of Kombucha tea. Biomed. Environ. Sci. 16: 276–282.
- EPA, 1999. Quality Criteria for Lead. Environmental Protection Agency.
- Ergurhan-Ilhan I, Cadir B, Koyuncu-Arslan M, Arslan C, Glutepe FM, Ozkan G. 2008. Level of oxidative stress and damage in erythrocytes in apprentices indirectly exposed to lead. Pediatr. Inti. 50: 45–50.
- Flohe L, Gunzler WA. 1984. Glutathione peroxidase. In Methods of Enzymology, Packer L (ed.), Vol. 105. Academic: Orlando, FL; 115–121.
- Flora SJ, Pande M, Mehta A. 2003. Beneficial effect of combined administration of some natuarally occurring antioxidants (vitamins) and thiol chelaters in the treatment of chronic lead intoxication. Chem. Bio. Interact. 145: 267–280.
- Garcon G, Leleu B, Marez T, Zerimech F, Haguenoer JM, Furon D, Shirali P. 2007. Biomonitoring of the adverse effects induced by the chronic exposure to lead and cadmium on kidyney function: Usefulness of alpha-glutatione S-transferase. Sci. Total. Environ. 377: 165–172.
- Garza A, Vega R, Soto E. 2006. Cellular mechanisms of lead neurotoxicity. Med. Sci. Monit. 12: 57–65.
- Gracia RC, Snodgrass WR. 2007. Lead toxicity and chelation therapy. Am. J. Health. Syst. Pharm. 64: 45–53.
- Griffith OW. 1980. Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinyl pyridine. Anal. Biochem. 106: 207–212.
- Gu Y, Wang L, Xiao C, Guo F, Ruan DY. 2005. Effects of lead on voltage-gated sodium channels in rat hippocampal CA1 neurons. Neuroscience. 133: 679–690.
- Gurer-Orhan H, Sabir HU, Ozgunes H. 2004. Correlation between clinical indicators of lead poisoning and oxidative stress parameters in controls and lead-exposed workers. Toxicology. 195: 147–154.
- Habig WH, Pabst M J, Jakoby WB. 1974. Glutathione-s-transferase: the first enzymatic step in mercapturic acid formation. J. Biol. Chem. 249: 7130–7193.
- Hu H, Woolf A. 2007. Recommendations for medical management of adult lead exposure. Environ. Health. Perspect. 115: 463–471.
- Huang J, Philbert MA. 1995. Distribution of glutathione and glutathione-related enzyme systems in mitochondria and cytosol of cultured cerebellar astrocytes and granule cells. Brain. Res. 680: 16–22.
- Johnson JA, elBarbary A, Kornguth SE, Brugge JF, Siegel FL. 1993. Glutathione S-transferase isoenzymes in rat brain neurons and glia. J. Neurosci. 13: 2013–2023.
- Kasperczyk S, Kasperczyk A, Ostalowska A, Dziwisz M, Biekner E. 2004. Activity of glutathione peroxidase, glutathione reductase and lipid peroxidation in erythrocytes in workers exposed to lead. Biol. Trace. Elem. Res. 102: 61–72.
- Kiran Kumar B, Brown E, McCormick R, Yallapragada PR, Sharada R, Rajanna B. 2008. Lead-induced increase in antioxidant enzymes and lipid peroxiation products in developing rat brain. Biometals. 21: 9–16.
- Legare ME, Barhoum R, Burghardt RC, Tiffany-Castiglioni E. 1993. Low level lead exposure in cultured astroglia: Identification of cellular targets with vital fluorescent probes. Neurotoxicology 14: 267–272.
- Lidsky TI, Schneider. 2003. Lead neurotoxicity in children: basic mechanisms and clinical correlates. Brain 126: 5–19.
- Lowry OW, Rosenbrough NJ, Farr AL, Randall RJ. 1951. Protein measurement with Folin phenol reagent. J. Biol. Chem. 193: 265–275.
- Martínez-Lara E, Siles E, Hernández R, Cañuelo AR, Luisa del Moral M, Jiménez A, Blanco S, López-Ramos JC, Esteban FJ, Pedrosa JA, Peinado MA. 2003. Glutathione S-transferase isoenzymatic response to aging in rat cerebral cortex and cerebellum. Neurobiol. Aging 24(3): 501–9.
- Meister A. 1988. Glutathione metabolism and its selective modification. J. Biol. Chem. 263: 17205–17208.
- Meister A. 1983. Glutathione. Annu. Rev. Biochem. 79: 711–790.
- Moreira EG, Vassilieff I, Vassilieff VS. 2001. Developmental lead exposure: Behavioral alterations in the short- and long-term. Neurotoxicol. Teratol. 23: 489–95.
- Moser R, Oberley TD, Daggett DA, Friedman AL, Johnson JA, Siegel FL. 1995. Effects of lead administration on developing rat kidney. I. Glutathione S-transferase isoenzymes. Toxicol. Appl. Pharmacol. 131: 85–93.
- Munoz C, Garbe K, Lileinthal H, Winneke G. 1988. Significance of hippocampal dysfunction in low level lead exposure of rats. Neurotoxicol. Teratol. 10: 245–253.
- Patrick L. 2006a. Lead toxicity. Part II: the role of free radical damage and the use of antioxidants in the pathology and treatment of lead toxicity. Altern. Med. Rev. 11: 114–127.
- Patrick L. 2006b. Lead toxicity, a review of the literature. Part 1: Exposure, evaluation, and treatment. Altern. Med. Rev. 11: 2–22.
- Penugonda S, Mare S, Lutz P, Banks WA, Ercal N. 2006. Potentiation of lead-induced cell death in PC12 cells by glutamate: protection by N-acetylcysteine amide (NACA), a novel thiol antioxidant. Toxicol. Appl. Pharmacol. 216(2): 197–205.
- Philbert MA, Beiswanger CM, Manson MM, Green JA, Novak RF, Primiano T, Reuhl KR, Lowndes HE. 1995. Glutathione S-transferase and gamma-glutamul transpeptidase in the rat nervous ststem: a basis for differential susceptibility to neurotoxicants. Neurotoxicology 16: 349–362.
- Rajanna B, Yallapragada PR, Hall E, Rajanna S. 1996. In vitro effect of lead on Ca2+-ATPase in synaptic plasma membranes and microsomes of rat cerebral cortex and cerebellum. Ecotoxicol. Environ. Saf. 33: 157–162.
- Rajanna B, Rajanna S, Hall E, Yallapragada PR. 1997. In vitro metal inhibition of N-methyl-d-aspartate specific glutamate receptor binding in neonatal and adult rat brain. Drug. Chem. Toxicol. 20: 21–29.
- Sagara J, Sugita Y. 2001. Characterization of cytosolic glutathione-S-transferases in cultured astrocytes. Brain Res. 902: 190–197.
- Sandhir R, Julka D, Gill KD. 1994. Lipoperoxidative damage on lead exposure in rat brain and its implications on membrane bound enzymes. Pharmacol. Toxicol. 74: 66–71.
- Saxena G, Flora SJ. 2006. Changes in brain biogenic amines and haem biosynthesis and their response to combined administration of succimers and Centella asiatica in lead poisoned rats. J. Pharm. Pharmacol. 58: 547–559.
- Schwartz BS, Hu H. 2007. Adult lead exposure: time for change. Environ. Health Perspect. 115: 451–454.
- Schwartz BS, Lee BK, Lee GS. 2000. Associations of blood lead, dimercaptosuccinic acid chelatable lead and tibia lead with polymorphisms in the vitamin D receptor and 5-aminolevulinic acid dehydratase genes. Environ. Health Perspect. 108: 949–954.
- Sivaprasad R, Nagaraj M, Varalakshmi P. 2003. Combined efficacies of lipoic acid and meso-2,3-dimercaptosuccinic acid on lead-induced erythrocyte membrane lipid peroxidation and antioxidant status in rats. Hum. Exp. Toxicol. 22: 183–192.
- Snedecor GW, Cochran WG. 1967. Statistical Methods. Iowa: The Iowa University Press.
- Struzynska L, Lenkiewicz A, Rafalowska U. 2001. Glutathione and glutathione-related enzymes in rat brain after acute lead exposure. Folia. Neuropathol. Suppl. A: 33–37.
- Struzynska L, Sulkowski G, Lenkiewicz A, Rafalowska U. 2002. Lead stimulates the glutathione system in the selective regions of rat brain. Folia. Neuropathol. 40(4): 203–209.
- Toscano CD, Guilarte TR. 2005. Lead neurotoxicity: from exposure to molecular effects. Brain Res. Rev. 49: 529–554.
- Villeda-Hernandez J, Barroso-Moguel R, Mendez-Armenta M, Nava-Ruiz C, Huerta-Romero R, Rios C. 2001. Enhanced brain regional lipid peroxidation in developing rats exposed to low level lead acetate. Brain Res. Bull. 55: 247–251.
- White LD, Cory-Slechta DA, Gilbert ME, Tiffany-Castiglioni E, Zawia NH, Virgolini M, Rossi-George A, Lasley SM, Qian YC, Basha MR. 2007. New and evolving concepts in the neurotoxicity of lead. Toxicol. Appl. Pharmacol. 225: 1–27.
- Woolf AD, Goldman R, Bellinger DC. 2007. Update on the clinical management of childhood lead poisoning. Pediatr. Clin. N. Am. 54: 271–294.
- Yallapragada PR, Butler J, Kiran Kumar B, Rajanna B. 2003. In vitro effect of lead on Na+, K+-ATPase activity in different regions of adult rat brain. Drug. Chem. Toxicol. 26: 117–124.
- Yang Y, Cheng J, Singhal SS, Saini M, Pandya U, Awasthi S, Awasthi YC. 2001. Role of glutathione-S-transferases in protection against lipid peroxidation. J. Biol. Chem. 276: 19220–19230.
- Zawia NH, Crumpton T, Brydie M, Reddy GR, Razmiafshari M. 2000. Disruption of the zinc finger domain: a common target that underlies many of the effects of lead. Neurotoxicol. 21: 1069–1080.
