title: N-acetyl-l-cysteine affords protection against lead-induced cytotoxicity and oxidative stress in human liver carcinoma (HepG2) cells.
abstract: Although lead exposure has declined in recent years as a result of change to lead-free gasoline, several epidemiological have pointed out that it represents a medical and public health emergency, especially in young children consuming high amounts of lead-contaminated flake paints. A previous study in our laboratory indicated that lead exposure induces cytotoxicity in human liver carcinoma cells. In the present study, we evaluated the role of oxidative stress in lead-induced toxicity, and the protective effect of the anti-oxidant n-acetyl-l-cysteine (NAC). We hypothesized that oxidative stress plays a role in lead-induced cytotoxicity, and that NAC affords protection against this adverse effect. To test this hypothesis, we performed the MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay and the trypan blue exclusion test for cell viability. We also performed the thiobarbituric acid test for lipid peroxidation. Data obtained from the MTT assay indicated that NAC significantly increased the viability of HepG2 cells in a dose-dependent manner upon 48 hours of exposure. Similar trend was obtained with the trypan blue exclusion test. Data generated from the thiobarbituric acid test showed a significant (p <or= 0.05) increase of MDA levels in lead nitrate-treated HepG2 cells compared to control cells. Interestingly, the addition of NAC to lead nitrate-treated HepG2 cells significantly decreased cellular content of reactive oxygen species (ROS), as evidenced by the decrease in lipid peroxidation byproducts. Overall, findings from this study suggest that NAC inhibits lead nitrate-induced cytotoxicity and oxidative stress in HepG2 cells. Hence, NAC may be used as a salvage therapy for lead-induced toxicity in exposed persons.
authors.affiliation: Molecular Toxicology Research Laboratory, NIH-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, Jackson, Mississippi, USA.
authors.forename: Clement G
authors.initials: CG
authors.lastname: Yedjou
authors.forename: Paul B
authors.initials: PB
authors.lastname: Tchounwou
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D049109:Cell Proliferation; D002470:Cell Survival; D002614:Chelating Agents; D005609:Free Radicals; D006801:Humans; D007854:Lead / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008113:Liver Neoplasms / Q000473:pathology*; D009154:Mutation; D009566:Nitrates / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D013858:Thiobarbiturates
chemical_list: D002614:Chelating Agents; D005609:Free Radicals; D009566:Nitrates; D013858:Thiobarbiturates; D007854:Lead; C017461:lead nitrate; C029684:thiobarbituric acid; D000111:Acetylcysteine