Sunday Aderemi Adelakun 1Babatunde Ogunlade 1Kingsley Afoke Iteire 2Opeyemi Zainab Kaka 1Kehinde Precious Adelusi1
作者信息
- 1. Department of Human Anatomy,Federal University of Technology,Akure 340001,Imo State,Nigeria
- 2. Department of Anatomy,University of Medical Science,Ondo 340101,Ondo State,Nigeria
- 折叠
摘要
Abstract
Background:Tramadol hydrochloride(TRM)is widely used to manage moderate to severe pain,but higher doses may cause adverse effects like cerebellar neurotoxicity.Sinapic acid(SA)is a natural phenolic acid with a strong antioxidant capacity and a promising candidate for preventing and treating neuronal injury.
Objective:This study focused on the effect of SA in excessive TRM exposure-induced cerebellar neurotoxicity.
Method:Thirty five rats were randomized into five groups(n=7):control(normal saline),TRM(50 mg/kg),SA(40 mg/kg),TRM+SA(post-treatment),and SA+TRM(pre-treatment),with daily intraperitoneal administration for 28 days.Cognitive function was assessed via the novel-object recognition and Y-maze tests.Cerebellar tissues were analyzed for its histopathological changes by Hematoxylin and Eosin(H&E)staining,as well as the levels of oxidative stress markers(Malondialdehyde(MDA)and nitric oxide(NO)),antioxidant enzymes(reduced glu-tathione(GSH),glutathione peroxidase(GPX)and superoxide dismutase(SOD)),inflammatory cytokines(tumor necrosis factor-alpha(TNF-α),nuclear-related factor 2(Nrf-2),cyclooxygenase-2(COX-2),interleukin-6(IL-6)and interleukin-1(IL-1)),neurotransmitters(acetylcholinesterase(AChE),norepinephrine(NE),dopamine(DA),serotonin(5-HT)and glutamate-dehydrogenase(GDH)),apoptotic markers(Caspase-3 and B-cell lymphoma(Bcl-2))by biochemical assays.
Results:TRM exposure impaired spatial and non-spatial memory,reduced body/brain weight,and induced cere-bellar damage,marked by increased oxidative stress(MDA,NO),pro-inflammatory cytokines,AChE activity,and apoptotic markers(Caspase-3),alongside decreased antioxidant enzyme activity and neurotransmitter levels(NE,DA,5-HT,GDH).Histology revealed degenerative changes in Purkinje cells and cortical layers.SA treatment(pre-and post-)significantly ameliorated cognitive deficits,restored body/brain weight,reduced oxidative stress and inflammation,normalized antioxidant and neurotransmitter profiles,and attenuated apoptosis.Histopathological analysis showed regeneration of Purkinje cells and improved cerebellar architecture in SA-treated groups.
Conclusion:Sinapic acid exerts significant neuro-therapeutic effects against TRM-induced neurotoxicity via ox-idative stress inhibition and down-regulation of inflammatory and apoptotic markers.关键词
盐酸曲马多/芥子酸/浦肯野细胞/小脑/氧化应激Key words
Tramadol hydrochloride/Sinapic acid/Purkinje cells/Cerebellum/Oxidative stress
