Pentoxifylline Ameliorates Function Of Oxidative Damage In The Brain Of Epilepsy Rats And The Involvement Of Nrf2-ARE Signaling Pathway

Epilepsy(Epilepsy,EP)is a common central nervous system disease,which is always accompanied by irregular electroencephalogram.Oxidative stress is an important mechanism of epileptic seizures and its continuous seizures.Antioxidants can reduce structural damage,reduce the number of seizures and alleviate cognitive deterioration.Therefore,antioxidant therapy is one of the means to relieve seizures.NF-E2 related factor 2(NF-E2-related factor 2,Nrf2)is a key factor in cell regulation of oxidative stress.Nrf2 can regulate the transcription of various antioxidant enzymes through Nrf2-ARE pathway,thereby reducing the oxidative damage of the body and playing an important role in protecting the brain.Pentoxifylline(PTX)is a powerful antioxidant.Recent studies have shown that PTX can alleviate oxidative damage in the brain of epileptic rats at the early stage of seizure,but it is not clear whether PTX plays an antioxidant role through activating Nrf2-ARE signaling pathway in the early stage of epileptic seizure.Objective: To observe the effects of PTX pretreatment on oxidative stress and Nrf2-ARE signaling pathway in the early stage of Li-Pc induced seizures in rats,and to explore whether Nrf2-ARE signaling pathway is involved in the improvement of PTX on the oxidative damage in the early stage of seizures induced by Li-Pc.Methods: This paper is based on the Li-Pc induced epileptic seizures in rats as the animal model.Detect the oxidative stress parameters(MDA,LPO)in SN and Hip by the spectrophotometry;determine the Nrf2 mRNA,HO-1mRNA and NQO-1 mRNA in SN and Hip by RT-PCR;measure the Nrf2,HO-1 and NQO-1 protein in SN and Hip by Western blot.Results:1.Oxidative stress parametersIn SN brain area,the contents of MDA and LPO in SE group were significantly higher than those in Con group,which increased by 56% and98% respectively(P < 0.01).MDA and LPO in PTX+SE group were significantly lower than those in SE group,which decreased by 29% and 46%respectively(P < 0.01).In Hip brain area,the contents of MDA and LPO in SE group were significantly higher than those in Con group,which increased by 77% and 86% respectively(P < 0.01).MDA and LPO in PTX+SE group were significantly lower than those in SE group,which decreased by 35% and44% respectively(P < 0.01).2.RT-PCRCompared with group Con,the Nrf2 mRNA,HO-1 mRNA and NQO-1mRNA contents in SN brain area and Hip brain area of SE group increased,and increased by 17% and 15%(P<0.05),17% and 18%(P < 0.01),18% and22%(P < 0.01),respectively.Compared with the SE group,the content of Nrf2 mRNA and HO-1 mRNA in the SN brain region of group PTX+SE rats increased by 10% and 11%(P < 0.05),respectively.3.Western blotCompared with group Con,the expression level of Nrf2 and HO-1 in SN brain area of SE group increased,increased by 41% and 67% respectively(P <0.01),and the expression of HO-1 and NQO-1 in Hip brain increased by 30%and 43%,respectively(P < 0.01).Compared with the SE group,the expression levels of Nrf2,HO-1 and NQO-1 in the SN brain region of the PTX+SE group increased by 9%,24% and 64% respectively(P < 0.05).Conclusion:PTX pretreatment can enhance the activation of Nrf2-ARE signaling pathway and improve the oxidative stress state in the brain of epileptic rats at early stage,which may be one of the mechanism of PTX preconditioning to protect the epileptic rats from Li-Pc induced injury,so as to reduce their seizures.