Effects of ursolic acid on oxidative stress and apoptosis in focal cerebral ischemia reperfusion in rats

Abstract

Objective To investigate the effects of ursolic acid (UA) on oxidative stress and apoptosis in focal cerebral ischemia reperfusion in rats. Methods One hundred and twenty SD rats were randomly divided into 6 groups: sham operation group, model group, and groups of 20, 40, 80 120 mg/kg UA, with 20 rats in each group. A model of focal cerebral ischemic reperfusion was induced using the intraluminal thread method. Drugs were administrated immediately via tail vein injection when the suture was inserted. At 6h later, the total antioxidative capacity (T-AOC), malondialdehyde (MDA) level, and the activity of creatine kinase (CK), lactate dehydrogenase (LDH) in the serum, and the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) in the ischemic cortex were measured. Apoptosis in the ischemic cortex was detected by TUNEL staining. Results Compared with the model group, the activity of CK (301.2±86.8 U/L, 258.5±58.4 U/L, 228.7 ± 49.2 U/L vs. 352.6±88.1 U/L), LDH (327.5±87.1 U/L, 288.6±69.5 U/L, 243.7±74.9 U/L vs. 395.4±98.6 U/L) in the serum in the groups of 40, 80 120 mg/kg UA were significantly decreased (P<0.05 or P<0.01), MDA (5.5±1.4 mmol/L, 4.8 ± 1.1 mmol/L, 4.4±1.3 mmol/L vs. 7.8±2.0 mmol/L) and T-AOC (9.4 ± 2.2 U/L, 10.5±2.9 U/L, 11.8±3.1 U/L vs. 8.0±2.1 U/L) were significantly increased (P<0.05 or P<0.01); the activity of SOD (10.1±2.7 U/mg, 11.6±2.5 U/mg vs. 6.9±2.6 U/mg),GSH-Px (12.9±2.9 U/mg, 14.2±3.2 U/mg vs. 9.5 ± 2.3 U/mg), CAT (3.3 ± 1.3 U/mg, 3.9±1.2 U/mg vs. 2.3±0.9 U/mg) in the ischemic cortex in the groups of 80 120 mg/kg UA were significantly increased (P<0.05 or P<0.01). TUNEL staining showed that apoptosis in the ischemic cortex in all the UA groups were significantly decreased compared with the model group. Conclusion UA could effectively enhance the activity of antioxidant enzymes and free radical scavenging capacity, ameliorate oxidative stress and inhibit apoptosis in focal cerebral ischemia reperfusion in rats. Key words: Brain ischemia; Reperfusion injury; Ursolic acid; Oxidative stress; Apoptosis; Rats