Analysis of the effect of pentoxifylline on oxidative stress in brains of epileptic rats based on Nrf2-ARE signaling pathway
10.16571/j.cnki.1008-8199.2020.02.007
- VernacularTitle: 基于Nrf2ARE信号通路探析己酮可可碱对癫痫大鼠脑内氧化应激的影响
- Author:
Guang-tao SUN
1
;
Xun-zhong QI
1
;
Chun-ying ZOU
1
;
Ke-jian WANG
1
;
Zuo-yi HUANG
1
Author Information
1. The Fourth Neurology Department, The First Affiliated Hospital of Jiamusi University, Jiamusi 154002, Heilongjiang, China
- Publication Type:Journal Article
- Keywords:
Nrf2-ARE signaling pathway;
pentoxifylline;
epilepsy;
oxidative stress
- From:
Journal of Medical Postgraduates
2020;33(2):144-148
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effects of pentoxifylline (PTX) on oxidative stress in brains of epileptic (EP) rats based on the nuclear factor E2 related factor 2 (Nrf2) antioxidant response element (ARE) signal pathway.MethodsThirty-six healthy and adult male Wistar rats were included in the experiment and were divided into blank control group (peritoneal injection of isotonic saline), EP control group (induced EP episode), and PTX group (induced EP episode ＋ PTX pretreatment) according to a completely random method, then 12 rats in each group. The behavioral changes of rats in each group were monitored, and the EP attack rate and seizure latency were recorded. The rats were sacrificed to collect substantia nigra and hippocampus for testing oxidative stress indicators and expression levels of Nrf2 ARE signaling pathway-related proteins.ResultsNo abnormal reaction was observed in the control group after treatment. The EP attack rate in the EP control group reached 83.33%. The EP attack rate (33.3%) and the attack level ((2.14±0.40) vs (3.09±0.58)) in the PTX group were significantly lower than those in the EP control group, and the seizure latency was significantly longer than that in the EP control group (P<0.05). Compared with the blank control group, the rats in the EP control group had significantly higher levels of malondialdehyde (MDA) in the substantia nigra and hippocampus, and significantly reduced glutathione (GSH) and superoxide dismutase (SOD) activities (P<0.05). Compared with EP control group, MDA content in substantia nigra and hippocampus of PTX group ((760.22±74.86) nmol/g vs (682.93±69.01) nmol/g·pro, (842.24±101.17) nmol/g·pro vs (705.46±80.87) nmol/g·pro) were significantly reduced, GSH ((68.31±12.57) μg/g·pro vs (94.43±14.11) μg/g·pro, (64.27±10.28) μg/g·pro vs (87.36±11.11) μg/g·pro), SOD ((95.34±8.72) U/mg·pro vs (120.60±10.04) U/mg·pro, (91.33±8.46) U/mg·pro vs (118.46±9.94) U/mg·pro) activity was significantly increased (P<0.05). Compared with the blank control group, the expressions of substantia nigra tissue, hippocampal Nrf2, and HO1 protein in the EP control group rats were significantly reduced (P<0.05); while the substantia nigra tissue and hippocampal Nrf2 protein in the PTX group were significantly increased compared with the EP control group ((0.72±0.09) vs (0.30±0.04), (0.34±0.06) vs (0.21±0.03)), HO 1 ((0.66±0.08) vs (0.34±0.05), (0.48±0.08) vs (0.31±0.05)), NQO1 protein expression was significantly increased ((0.48±0.07) vs (0.25±0.06), (0.78±0.11) vs (0.68±0.07), P<0.05), and the expression of hippocampal tissue returned to the blank control group (P>0.05) ). The expression of substantia nigra tissue was significantly higher than that of the blank control group (P<0.05).ConclusionPTX can inhibit EP seizure and improve the oxidative stress in the brain of rats at the early stage of EP. The possible mechanism is that PTX can specifically activate Nrf2 ARE signaling pathway.
