title: Citric acid effects on brain and liver oxidative stress in lipopolysaccharide-treated mice.
abstract: Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 μg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-α) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1-2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-α, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1-2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1-2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.
authors.affiliation: 1 Department of Toxicology and Narcotics, National Research Center , Cairo, Egypt.
authors.forename: Omar M E
authors.initials: OM
authors.lastname: Abdel-Salam
authors.forename: Eman R
authors.initials: ER
authors.lastname: Youness
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Mohammed
authors.forename: Safaa M Youssef
authors.initials: SM
authors.lastname: Morsy
authors.forename: Enayat A
authors.initials: EA
authors.lastname: Omara
authors.forename: Amany A
authors.initials: AA
authors.lastname: Sleem
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D043303:Aryldialkylphosphatase / Q000032:analysis; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D053148:Caspase 3 / Q000032:analysis; D019343:Citric Acid / Q000627:therapeutic use*; D053938:DNA Fragmentation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000032:analysis; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008107:Liver Diseases / Q000517:prevention & control; D008297:Male; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D009573:Nitrites / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects*; D010537:Peritoneum / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008070:Lipopolysaccharides; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D019343:Citric Acid; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; D043303:Aryldialkylphosphatase; D053148:Caspase 3
keywords: antioxidant activity; citric acid; cytokines; dietary supplementation; peripheral infection; systemic inflammation