ABSTRACT
OBJECTIVE@#To investigate the effect of acute renal ischemia reperfusion on brain tissue.@*METHODS@#Fourty eight rats were randomly divided into four groups (n=12): sham operation group, 30 min ischemia 60 min reperfusion group, 60 min ischemia 60 min reperfusion group, and 120 min ischemia 60 min reperfusion group. The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.@*RESULTS@#Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time. The detection at the molecular level showed decreased Bcl-2 expression, increased Bax expression, upregulated expression of NF-κB and its downstream factor COX-2/PGE2.@*CONCLUSIONS@#Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation.
Subject(s)
Animals , Male , Rats , Acute Kidney Injury , Metabolism , Apoptosis Regulatory Proteins , Metabolism , Brain , Cell Biology , Metabolism , Brain Chemistry , Cytokines , Metabolism , NF-kappa B , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Rats, Sprague-Dawley , Reperfusion Injury , MetabolismABSTRACT
The present study examined the inhibitory effect of licorice compounds glycyrrhizin and a metabolite 18 beta-lycyrrhetinic acid on the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse and on the 1-methyl-4-phenylpyridinium (MPP+-induced cell death in differentiated PC12 cells. MPTP treatment increased the activities of total superoxide dismutase, catalase and glutathione peroxidase and the levels of malondialdehyde and carbonyls in the brain compared to control mouse brain. Co-administration of glycyrrhizin (16.8 mg/kg) attenuated the MPTP effect on the enzyme activities and formation of tissue peroxidation products. In vitro assay, licorice compounds attenuated the MPP+induced cell death and caspase-3 activation in PC12 cells. Glycyrrhizin up to 100 micrometer significantly attenuated the toxicity of MPP+ Meanwhile, 18beta-lycyrrhetinic acid showed a maximum inhibitory effect at 10 micrometer; beyond this concentration the inhibitory effect declined. Glycyrrhizin and 18beta-lycyrrhetinic acid attenuated the hydrogen peroxide- or nitrogen species-induced cell death. Results from this study indicate that glycyrrhizin may attenuate brain tissue damage in mice treated with MPTP through inhibitory effect on oxidative tissue damage. Glycyrrhizin and 18 beta-lycyrrhetinic acid may reduce the MPP+toxicity in PC12 cells by suppressing caspase-3 activation. The effect seems to be ascribed to the antioxidant effect.