Combination antiretroviral therapy (cART)-induced hippocampal disorders: Highlights on therapeutic potential of Naringenin and Quercetin
Combination antiretroviral therapy (cART)-induced hippocampal disorders: Highlights on therapeutic potential of Naringenin and Quercetin
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DOI：
10.1016/j.ibror.2019.04.002
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发表时间：
2019-06-01
期刊：
影响因子：
2.6
通讯作者：
Akanmu, Alani S.
中科院分区：
文献类型：
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作者：
Akang, Edidiong N.;Dosumu, Olufunke O.;Akanmu, Alani S.
简介：尽管联合抗逆转录病毒疗法（cART）对HIV阳性患者有多种益处，但据报道，长期使用会加剧氧化应激，并诱导神经和认知功能障碍，因此，需要寻找一种辅助疗法来改善氧化和改善治疗依从性，并获得更好的病毒学结果。本研究旨在确定槲皮素和柚皮素对cART诱导的成年Wister大鼠海马中细胞结构、神经行为和免疫组织化学变化的潜在治疗作用。口服施用对照、DMSO、24 mg/kg cART（替诺伏韦300 mg、拉米夫定300 mg和依法韦仑600 mg）、50 mg/kg柚皮素、50 mg/kg槲皮素、cART+柚皮素、cART+槲皮素8周。在给药结束时，进行神经行为测试，动物被安乐死和海马处理的氧化应激标志物，组织学，TNF-α，和单胺氧化酶-Bexpression.Results：在8周的管理结束时，24 mg/kg的cART降低超氧化物歧化酶（SOD），过氧化氢酶（CAT），还原型谷胱甘肽（GSH）和增加丙二醛（MDA）。而50 mg/kg槲皮素和50 mg/kg柚皮素可降低cART诱导的氧化应激（增加SOD、CAT、GSH和降低MDA）（降低SOD、CAT、GSH和增加MDA）。此外，苏木精和伊红染色的海马显示，槲皮素和柚皮素防止cART处理的大鼠中的神经退行性变化（齿状回和角氨区域中的显著细胞质收缩和几个固缩核）。此外，免疫组织化学研究表明，槲皮素和柚皮素减弱cART诱导的单胺氧化酶-B（MAO-B）表达的上调。同样，从Morris水迷宫神经行为研究，柚皮素和槲皮素也改善cART诱导的记忆障碍（初始空间记忆，反转空间记忆和探针测试）。结论：这项研究表明，柚皮素和槲皮素有很好的潜力，在逆转cART诱导的Wistar大鼠海马疾病。
Introduction: In spite of the multiple benefits of combination antiretroviral therapy (cART) on HIV positive patients, prolonged usage has been reported to exacerbate oxidative stress, and induce neurological and cognitive dysfunction, thus, the need to search for an adjuvant therapy to ameliorate the oxidative and improve treatment adherence with better virological outcome. This study aimed at determining the potential therapeutic effects of Quercetin and Naringenin on cART-induced cyto-architectural, neuro-behavioral and immunohistochemical changes in the hippocampus of the adult Wister rats.Materials and Methods: The animals were grouped as follows: Control, DMSO, 24 mg/kg cART (Tenovovir 300 mg, Lamivudine 300 mg and Efavirenz 600 mg), 50 mg/kg Naringenin, 50 mg/kg Quercetin, cART+ Naringenin, cART+ Quercetin were administered orally for 8 weeks. At the end of administration, neurobehavioural test was conducted, animals were euthanized and hippocampus was processed for oxidative stress markers, histology, TNF-alpha, and Monoamine oxidase-B expression.Results: At the end of 8 weeks of administration, 24 mg/kg cART decreased superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and increased Malondialdehyde (MDA). Whereas, 50 mg/kg quercetin, and 50 mg/kg Naringenin decreased the oxidative stress (increased SOD, CAT, GSH, and reduced MDA) induced by cART (reduced SOD, CAT, GSH, and increased MDA). In addition, hematoxylin and eosin stained hippocampus showed that quercetin and naringenin prevented neurodegenerative changes (marked cytoplasmic shrinkage and several pyknotic nuclei in the dentate gyrus and cornus ammonis regions) in cART-treated rats. Furthermore, immunohistochemical studies revealed that quercetin and naringenin attenuates cART-induced upregulation of monoamine oxidase-B (MAO-B) expression. Likewise, from the Morris water maze neurobehavioral studies, naringenin and quercetin also ameliorated cART-induced memory impairments (initial spatial memory, reversal spatial memory and probe tests).Conclusion: This study shows that Naringenin and Quercetin have a good potential in reversing cART-induced hippocampal disorders in Wistar rats.