Citric Acid Protects Dopaminergic Cells against Rotenone-Induced Neurodegeneration

Abstract

We investigated the effect of citric acid on rotenone-induced oxidative stress and neuro- and hepato-toxicity. Swiss mice received subcutaneous injections of rotenone at a dose of 1.5 mg/kg once every other day for two weeks either alone or in combination with citric acid at 200 or 400 mg/kg given orally. The control group was treated with the vehicle dimethyl sulfoxide. The brain and liver levels of the lipid peroxidation product malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (TAC), and paraoxonase-1 (PON-1) activity were measured and as well as brain striatal concentrations of nuclear factor-kappa B (NF-kB) and tyrosine hydroxylase. Histopathology of the brain and liver tissue was also performed. Results indicated that MDA and NO content were increased whereas TAC and PON-1 decreased in the brain and liver tissue following rotenone injection. There was also increased NF-kB and decreased tyrosine hydroxylase concentrations in the brain of rotenone-treated mice. Rotenone-treated mice showed decreased striatal cell size and pyknotic nuclei. There were also interstitial hemorrhage and focal inflammatory cells infiltration in cerebral cortex, and degenerated neurons in cortex and hippocampus. The liver exhibited inflammatory cell infiltration and fibrosis. The administration of citric acid protected against rotenone-induced histopathological changes, decreased MDA, NO, and increased TAC and PON-1 activity in the brain and liver. It also reduced NF-kB and increased tyrosine hydroxylase in the brain of rotenone-treated mice. These data indicate that citric acid prevents rotenone-induced neuronal and liver damage via a decrease in oxidative stress. These findings suggest that supplementation with citric acid could be of value in the prevention of neuronal cell death in Parkinson’s disease.