Dooka Baridoo Donatus, Orish Chinna N, Ezejiofor Anthonet N, Umeji Theresa C, Nkpaa Kpobari W, Okereke Ifeoma, Cirovic Ana, Cirovic Aleksandar, Orisakwe Orish E
African Centre of Excellence for Public Health and Toxicological Research (ACE-PUTOR), University of Port Harcourt, PMB 5323, Choba 500102, Port Harcourt, Nigeria.
Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Port Harcourt, PMB, 5323, Choba 500102, Port Harcourt, Nigeria.
Toxicol Res (Camb). 2025 Apr 7;14(2):tfaf049. doi: 10.1093/toxres/tfaf049. eCollection 2025 Apr.
The hippocampus executes the integration of memory and spatial learning information. This study evaluated the effect of rice bran extract (RBE) on heavy metal mixture (MM) induced hippocampal toxicity and its underlying mechanism in albino rats. Thirty five rats were exposed to MM alone at Pb 20 mg/kg, Al 35 mg/kg, and Mn 0.564 mg/kg body weight or co-exposed with RBE at 125, 250 and 500 mg/kg body weight, 125 RBE mg/kg b.wt only, and 500 RBE mg/kg b.wt only 5 days a wk for 13 wk (90 days). Subsequently, oxidative stress, inflammation (cyclooxygenase-2) and caspase-3, amyloid precursor proteins (Aβ40 and Aβ42), HMOX-1, occludin and BDNF and transcription factor Nrf-2 in the hippocampus were investigated. MM treatment resulted in significantly higher escape latency time than both the control and MM plus RBE group. MM exposure induced increased oxidative stress, inflammation resulting in enhanced hippocampal apoptosis. MM significantly increased bioaccumulation of Pb, Al, and Pb; increased caspase-3, Nrf-2, Aβ40 and Aβ42 and significantly decreased occludin, BDNF, HMOX-1 when compared with the control. All these effects were reversed by RBE. Collectively, RBE ameliorated MM - induced oxidative stress, neuro-inflammation and hippocampal apoptosis via attenuation of oxidative damages of cellular constituents, neuronal inflammation and subsequent down regulation of amyloid precursor proteins Aβ40, Aβ42 and up regulation of occludin, BDNF, HMOX-1 protein expression via Nrf-2 dependent pathways to abrogate hippocampal toxicity associated with spatial learning and memory deficits.
海马体负责记忆与空间学习信息的整合。本研究评估了米糠提取物（RBE）对重金属混合物（MM）诱导的白化大鼠海马体毒性的影响及其潜在机制。35只大鼠单独暴露于MM，剂量为铅20毫克/千克、铝35毫克/千克和锰0.564毫克/千克体重，或与RBE共同暴露，RBE剂量分别为125、250和500毫克/千克体重，仅125毫克/千克体重的RBE，以及仅500毫克/千克体重的RBE，每周5天，共13周（90天）。随后，对海马体中的氧化应激、炎症（环氧化酶-2）和半胱天冬酶-3、淀粉样前体蛋白（Aβ40和Aβ42）、血红素加氧酶-1、闭合蛋白、脑源性神经营养因子（BDNF）以及转录因子Nrf-2进行了研究。与对照组和MM加RBE组相比，MM处理导致逃避潜伏期时间显著更长。MM暴露诱导氧化应激增加、炎症反应，导致海马体凋亡增强。与对照组相比，MM显著增加了铅、铝和锰的生物蓄积；增加了半胱天冬酶-3、Nrf-2、Aβ40和Aβ42，并显著降低了闭合蛋白、BDNF、血红素加氧酶-1。所有这些效应均被RBE逆转。总体而言，RBE通过减轻细胞成分的氧化损伤、神经元炎症以及随后通过Nrf-2依赖途径下调淀粉样前体蛋白Aβ40、Aβ42并上调闭合蛋白、BDNF、血红素加氧酶-1蛋白表达，改善了MM诱导的氧化应激、神经炎症和海马体凋亡，从而消除与空间学习和记忆缺陷相关的海马体毒性。
