Abstract

To investigate the damaging effect and action mechanism of the food additive citric acid (CA) on mouse liver, 40 healthy male Kunming mice were randomly divided into control group (0.9% saline), low CA dose (120mg/kg), middle dose (240mg/kg) and high dose groups (480mg/kg). All experimental mice have received peritoneal injection of the corresponding reagent each week for 3weeks. After 7days since the third injection, morphological changes were observed by light microscope; activities of T-SOD, glutathione peroxidase (GSH-Px), caspase-3, and contents of hydrogen peroxide (H2O2) and malonyldialdehyde (MDA) in the liver were evaluated using the corresponding assay kits; DNA fragmentation was assayed using agarose gel electrophoresis. Microscopical detection showed a series of hispathological changes in mouse livers treated with CA, such as indiscriminate liver cell cord, blood clot in central veins, and lymphocyte infiltrating. Biochemical examination suggested the gradually but moderately reduced T-SOD activity and elevated H2O2 level with the increase of CA dose (P>0.05), and the gradually reduced GSH-Px activity and increased MDA content depending on graded doses with a significant difference (P<0.05) between the high dose group and the control group. According to cell apoptosis assays, caspase-3 activity were significantly higher in all treatment groups than in the control (P<0.05) in a dose-dependent manner. Contrasting to the control, characteristic DNA laddering was observed when injected with any of the three graded doses. It can be concluded that certain concentrations of CA cause oxidative damage of the liver by means of the decrease of antioxidative enzyme activities, thus resulting in MDA level elevation and DNA fragmentation inducing active caspase-3.

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