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<p>Exposure to heavy metal mixtures (MM) pose significant public health concern due to their adverse health risks. Rice bran extract (RBE) elicits antioxidants, anti-inflammatory and antiapoptotic properties. This study has evaluated the neuroprotective properties of RBE on MM induced cerebral dysfunction and its underlying cellular mechanisms. Thirty-five rats were exposed to MM alone at Pb 20&#xa0;mg/kg, Al 35&#xa0;mg/kg, and Mn 0.564&#xa0;mg/kg body weight or co-exposed with RBE at 125, 250 and 500&#xa0;mg/kg body weight, 125 RBE mg/kg b.wt only, and 500 RBE mg/kg b.wt only 5&#xa0;days a week for 13&#xa0;weeks (90&#xa0;days). Thereafter, antioxidants, lipid peroxidation, inflammation (cyclooxygenase-2) and protein levels of occludin, amyloid precursor proteins (Aβ40 and Aβ42), apoptotic marker (caspase-3), HMOX-1, BDNF and transcription factor Nrf-2 in the cerebral cortex were investigated. Our results showed that RBE co-administration with MM reversed MM induced diminution of antioxidants and decreased lipid peroxidation, cyclooxygenase-3, caspase-3. Furthermore, our results shows that MM alone significantly increased bioaccumulation of Pb, Al, Mn in the cerebral cortex, increased levels of Aβ40, Aβ42 and Nrf-2 as well as significantly decreased BDNF, occlude in and HMOX-1 in comparison to the control. All these were reversed by RBE. Taken together, RBE abated MM-induced oxidative stress, neuronal inflammation and cerebral apoptosis via regulation of amyloid precursor proteins, BDNF, HMOX-1 via Nrf-2 dependent pathways to reversed MM induced cerebral toxicity.</p> Graphical abstract <p></p>

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Rice bran extract ameliorates metal mixture induced cerebral cortex dysfunction: implicating the Nrf-2/HMOX-1/BDNF signalling pathway

  • 期刊论文

  • 发表日期：

    2025年11月3日

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  • Baridoo Donatus Dooka,
  • Chinna N. Orish,
  • Anthonet N. Ezejiofor,
  • Theresa Umeji,
  • Kpobari W. Nkpaa,
  • Ifeoma Okereke,
  • Ana Cirovic,
  • Aleksandar Cirovic,
  • Orish E. Orisakwe

摘要

Exposure to heavy metal mixtures (MM) pose significant public health concern due to their adverse health risks. Rice bran extract (RBE) elicits antioxidants, anti-inflammatory and antiapoptotic properties. This study has evaluated the neuroprotective properties of RBE on MM induced cerebral dysfunction and its underlying cellular mechanisms. 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 week for 13 weeks (90 days). Thereafter, antioxidants, lipid peroxidation, inflammation (cyclooxygenase-2) and protein levels of occludin, amyloid precursor proteins (Aβ40 and Aβ42), apoptotic marker (caspase-3), HMOX-1, BDNF and transcription factor Nrf-2 in the cerebral cortex were investigated. Our results showed that RBE co-administration with MM reversed MM induced diminution of antioxidants and decreased lipid peroxidation, cyclooxygenase-3, caspase-3. Furthermore, our results shows that MM alone significantly increased bioaccumulation of Pb, Al, Mn in the cerebral cortex, increased levels of Aβ40, Aβ42 and Nrf-2 as well as significantly decreased BDNF, occlude in and HMOX-1 in comparison to the control. All these were reversed by RBE. Taken together, RBE abated MM-induced oxidative stress, neuronal inflammation and cerebral apoptosis via regulation of amyloid precursor proteins, BDNF, HMOX-1 via Nrf-2 dependent pathways to reversed MM induced cerebral toxicity.

Graphical abstract