Rice bran extract ameliorate heavy metal mixture induced hippocampal toxicity via inhibiting oxido-inflammatory damages and modulating Hmox-1/BDNF/Occludin/Aβ40/Aβ42 in rats.

Abstract

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.