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

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.