Abstract
The neurotoxicity of lead has been well established through numerous studies. However, the cellular processes of lead neurotoxicity, as well as techniques to prevent or reverse cellular damage after lead exposure, remain unknown. If oxidative stress plays a primary role in lead-induced neurotoxicity, antioxidants should assist in reviving lead-exposed cells. The present study explores N-acetylcysteine (NAC) as an antioxidant agent in PC-12 cells after lead exposure. Selective oxidative stress parameters, including glutathione (GSH), glutathione disulfide (GSSG), and malondialdehyde (MDA), were measured in PC-12 cells exposed to various concentrations of lead acetate. Administering NAC after lead exposure improved cell survival as measured by Trypan Blue exclusion. NAC treatment also increased the GSH/GSSG ratio compared to the lead-only group, and reduced MDA to near control levels. These results imply that NAC protects cells from lead-induced oxidative damage by boosting the PC-12 cells’ antioxidant defense mechanisms.
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References
MT Antonio ML Leret (2000) ArticleTitleStudy of the neurochemical alterations produced in discrete brain areas by perinatal low-level lead exposure Life Sci 67 635–642
MM Bradford (1976) ArticleTitleA rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding Anal Biochem 72 248–254
JP Bressler L Belloni-Olivi S Forman GW Goldstein (1996) ArticleTitleDistinct mechanisms of neurotransmitter release from PC 12 cells exposed to lead J Neurosci Res 46 678–685
HH Draper EJ Squires H Mahmoodi J Wu S Agarwal M Hadley (1993) ArticleTitleA comparative evaluation of thiobarbituric acid methods for the determination of malondialdehyde in biological materials Free Radic Biol Med 15 353–363
W Droge K Schulze-Osthoff S Mihm D Galter H Schenk HP Eck S Roth H Gmunder (1994) ArticleTitleFunctions of glutathione and glutathione disulfide in immunology and immunopathology FASEB J 8 1131–1138
N Ercal P Treeratphan TC Hammond RH Matthews NH Grannemann DR Spitz (1996a) ArticleTitleIn vivo indices of oxidative stress in lead-exposed C57BL/6 mice are reduced by treatment with meso-2,3-dimercaptosuccinic acid or N-acetylcysteine Free Radic Biol Med 21 157–161
N Ercal P Treeratphan P Lutz TC Hammond RH Matthews (1996b) ArticleTitleN-acetylcysteine protects Chinese hamster ovary (CHO) cells from lead-induced oxidative stress Toxicology 108 57–64
RA Goyer (1993) ArticleTitleLead toxicity: current concerns Environ Health Perspect 100 177–187
H Gurer N Ercal (2000) ArticleTitleCan antioxidants be beneficial in the treatment of lead poisoning? Free Radic Biol Med 29 927–945
H Gurer H Ozgunes S Oztezcan N Ercal (1999) ArticleTitleAntioxidant role of alpha-lipoic acid in lead toxicity Free Radic Biol Med 27 75–81
CC Hegg V Miletic (1998) ArticleTitleDiminished blocking effect of acute lead exposure on high-threshold voltage-gated calcium currents in PC12 cells chronically exposed to the heavy metal Neurotoxicology 19 413–420
A Hilliard A Ramesh NH Zawia (1999) ArticleTitleCorrelation between lead-induced changes in cerebral ornithine decarboxylase and protein kinase C activities during development and in cultured PC 12 cells Int J Dev Neurosci 17 777–785
HV Hirsch J Mercer H Sambaziotis M Huber DT Stark T Torno-Morley K Hollocher H Ghiradella DM Ruden (2003) ArticleTitleBehavioral effects of chronic exposure to low levels of lead in Drosophila melanogaster Neurotoxicology 24 435–442
D Holtzman JE Olson C DeVries K Bensch (1987) ArticleTitleLead toxicity in primary cultured cerebral astrocytes and cerebellar granular neurons Toxicol Appl Pharmacol 89 211–225
MM Hossain A Takashima H Nakayama K Doi (1997) ArticleTitle5-Azacytidine induces toxicity in PC12 cells by apoptosis Exp Toxicol Pathol 49 201–206
GS Kelly (1998) ArticleTitleClinical applications of N-acetylcysteine Altern Med Rev 3 114–127
K Kim M Annadata GW Goldstein JP Bressler (1997) ArticleTitleInduction of c-fos mRNA by lead in PC 12 cells Int J Dev Neurosci 15 175–182
AM Kuzirian HT Epstein D Buck FM Child T Nelson DL Alkon (2001) ArticleTitlePavlovian conditioning-specific increases of the Ca2+- and GTP-binding protein, calexcitin in identified Hermissenda visual cells J Neurocytol 30 993–1008
JJ Loikkanen J Naarala KM Savolainen (1998) ArticleTitleModification of glutamate-induced oxidative stress by lead: the role of extracellular calcium Free Radic Biol Med 24 377–384
R Neal K Cooper G Kellogg H Gurer N Ercal (1999) ArticleTitleEffects of some sulfur-containing antioxidants on lead-exposed lenses Free Radic Biol Med 26 239–243
HL Needleman A Schell D Bellinger A Leviton EN Allred (1990) ArticleTitleThe long-term effects of exposure to low doses of lead in childhood An 11-year follow-up report. N Engl J Med 322 83–88
LA Opanashuk JN Finkelstein (1995) ArticleTitleRelationship of lead-induced proteins to stress response proteins in astroglial cells J Neurosci Res 42 623–632
K Oravecz E Bazso-Dombi F Jeney K Nagy M Gecse I Zs-Nagy (2001) ArticleTitleThe involvement of hydroxyl free radicals in differentiation of the PC-12 rat pheochromocytoma cell line Arch Gerontol Geriatr 33 61–69
GT Ramesh SK Manna BB Aggarwal AL Jadhav (1999) ArticleTitleLead activates nuclear transcription factor-kappaB, activator protein-1, and amino-terminal c-Jun kinase in pheochromocytoma cells Toxicol Appl Pharmacol 155 280–286
LA Ridnour RA Winters N Ercal DR Spitz (1999) ArticleTitleMeasurement of glutathione, glutathione disulfide, and other thiols in mammalian cell and tissue homogenates using high-performance liquid chromatography separation of N-(1-pyrenyl)maleimide derivatives Methods Enzymol 299 258–267
JA Salinas NC Huff (2002) ArticleTitleLead and conditioned fear to contextual and discrete cues Neurotoxicol Teratol 24 541–550
KR Shelton JM Todd PM Egle (1986) ArticleTitleThe induction of stress-related proteins by lead J Biol Chem 261 1935–1940
JB Suszkiw (2004) ArticleTitlePresynaptic disruption of transmitter release by lead Neurotoxicology 25 599–604
K Suzukawa K Miura J Mitsushita J Resau K Hirose R Crystal T Kamata (2000) ArticleTitleNerve growth factor-induced neuronal differentiation requires generation of Rac1-regulated reactive oxygen species J Biol Chem 275 13175–13178
J Wakefield (2002) ArticleTitleThe lead effect? Environ Health Perspect 110 A574–A580
TM Williams AM Ndifor JT Near RR Reams-Brown (2000) ArticleTitleLead enhances NGF-induced neurite outgrowth in PC12 cells by potentiating ERK/MAPK activation Neurotoxicology 21 1081–1089
RA Winters J Zukowski N Ercal RH Matthews DR Spitz (1995) ArticleTitleAnalysis of glutathione, glutathione disulfide, cysteine, homocysteine, and other biological thiols by high-performance liquid chromatography following derivatization by n-(1-pyrenyl)maleimide Anal Biochem 227 14–21
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Aykin-Burns, N., Franklin, E.A. & Ercal, N. Effects of N-Acetylcysteine on Lead-Exposed PC-12 Cells. Arch Environ Contam Toxicol 49, 119–123 (2005). https://doi.org/10.1007/s00244-004-0025-0
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DOI: https://doi.org/10.1007/s00244-004-0025-0