title: In vitro assessment of hepatoprotective agents against damage induced by acetaminophen and CCl4.
abstract: BACKGROUND
  In vitro bioassays are important in the evaluation of plants with possible hepatoprotective effects. The aims of this study were to evaluate the pretreatment of HepG2 cells with hepatoprotective agents against the damage induced by carbon tetrachloride (CCl4) and paracetamol (APAP).
  
  
  METHODS
  Antioxidative activity was measured using an assay to measure 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. The in vitro hepatotoxicity of CCl4and APAP, and the cytotoxic and hepatoprotective properties of silymarin (SLM), silybinin (SLB), and silyphos (SLP) were evaluated by measuring cell viability; activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH); total antioxidant capacity (TAOxC); and reduced glutathione (GSH), superoxide dismutase (SOD), and lipid peroxidation (malondialdehyde (MDA) levels).
  
  
  RESULTS
  Only SLB and SLM showed strong antioxidative activity in the DPPH assay (39.71 ± 0.85 μg/mL and 14.14 ± 0.65 μg/mL, respectively). CCl4induced time- and concentration-dependent changes. CCl4had significant effects on cell viability, enzyme activities, lipid peroxidation, TAOxC, and SOD and GSH levels. These differences remained significant up to an exposure time of 3 h. APAP induced a variety of dose- and time-dependent responses up to 72 h of exposure. SLM, SLB, and SLP were not cytotoxic. Only SLB at a concentration of 100 μg/mL or 150 μg/mL significantly decreased the enzyme activities and MDA level, and prevented depletion of total antioxidants compared with CCl4.
  
  
  CONCLUSIONS
  CCl4was more consistent than APAP in inducing cell injury. Only SLB provided hepatoprotection. AST, LDH, and MDA levels were good markers of liver damage.
authors.affiliation: Liver Unit, Gastroenterology Service, Department of Internal Medicine, University Hospital "Dr. José E. González", Av. Gonzalitos #235 Col. Mitras Centro C.P., 64460, Monterrey, Nuevo León, Mexico.
authors.forename: Liliana Torres
authors.initials: LT
authors.lastname: González
authors.affiliation: Department of Analytical Chemistry, School of Medicine, Universidad Autónoma de Nuevo León, Av. Madero y Aguirre Pequeño S/N, Col. Mitras Centro, C. P., 64460, Monterrey, N. L., Mexico.
authors.forename: Noemí Waksman
authors.initials: NW
authors.lastname: Minsky
authors.affiliation: Liver Unit, Gastroenterology Service, Department of Internal Medicine, University Hospital "Dr. José E. González", Av. Gonzalitos #235 Col. Mitras Centro C.P., 64460, Monterrey, Nuevo León, Mexico.
authors.forename: Linda Elsa Muñoz
authors.initials: LE
authors.lastname: Espinosa
authors.affiliation: Department of Analytical Chemistry, School of Medicine, Universidad Autónoma de Nuevo León, Av. Madero y Aguirre Pequeño S/N, Col. Mitras Centro, C. P., 64460, Monterrey, N. L., Mexico.
authors.forename: Ricardo Salazar
authors.initials: RS
authors.lastname: Aranda
authors.affiliation: Department of Analytical Chemistry, School of Medicine, Universidad Autónoma de Nuevo León, Av. Madero y Aguirre Pequeño S/N, Col. Mitras Centro, C. P., 64460, Monterrey, N. L., Mexico.
authors.forename: Jonathan Pérez
authors.initials: JP
authors.lastname: Meseguer
authors.affiliation: Liver Unit, Gastroenterology Service, Department of Internal Medicine, University Hospital "Dr. José E. González", Av. Gonzalitos #235 Col. Mitras Centro C.P., 64460, Monterrey, Nuevo León, Mexico. paucordero@yahoo.com.mx.
authors.forename: Paula Cordero
authors.initials: PC
authors.lastname: Pérez
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000410:Alanine Transaminase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008315:Malondialdehyde / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*
chemical_list: D010936:Plant Extracts; D020011:Protective Agents; D000082:Acetaminophen; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione
keywords: Acetaminophen; Carbon tetrachloride; HepG2 cell line; Hepatoprotective; Silybinin; Silymarin; Silyphos