Neuroprotective properties of rice bran extract against heavy metal mixture-induced cerebellar toxicity via regulation of Nrf-2/HMOX-1/BDNF pathways in rats.

Barido Donatus Dooka, Chinna N Orish, Anthonet N Ezejiofor, Tochukwu Thaddeus Ugwu, Kpobari W Nkpaa, Ifeoma Okereke, Ana Cirovic, Orish E Orisakwe

J Trace Elem Med Biol

Jun 13, 2026

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Abstract

OBJECTIVE: Rice bran extract (RBE) contains proteins, carbohydrates and other nutrients and active compositions such as phenolic acids, non-starch polysaccharides, tocotrienols, tocopherols, phytic acid and c-oryzanol which contains antioxidant and anticancer activities. This present study aimed at investigating the neuroprotective mechanism of RBE in chronically treated with metal mixture (MM) or orally co-treated with RBE at 125, 250 and 500 mg/kg body weight for 5 days a week for 13 weeks (90 days). METHODS: Thirty five rats were divided into seven groups of 5 rats per group namely control, MM alone (Pb 20, Al 35, and Mn 0.564 mg / kg body weight), MM plus RBE 125 mg/kg, MM plus RBE 250 mg/kg and MM plus RBE 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).The rats were euthanised under ip pentobarbital anaesthesia and cerebellum of the rats were excised and antioxidant enzymes, oxidative stress markers, neuroinflammatory marker (COX-2), brain - derived neurotrophic factor (BDNF), heme oxygenase - 1 (HOMX-1), occludin, pro-apoptotic marker (caspase - 3), amyloid precursor proteins (Aβ-40 and Aβ-42) and transcription factor Nrf-2 were assayed in the cerebellar cortex of the rats. RESULT: MM treated group showed significantly lower scores than the control group in the rotarod test. Exposure to MM significantly increased the levels of Pb, Al and Mn and co-treatment with RBE significantly decreased the levels of Pb, Al and Mn in the cerebellum. RBE abated MM - mediated decrease in antioxidant enzymes, BDNF, and HMOX-1, Aβ-40 and Aβ-42 levels and increase MDA, COX-2, occludin, caspase - 3 and Nrf-2 activation in rats' cerebellum. CONCLUSION: RBE may be a prospective therapeutic agent against cerebellar toxicity associated with MM poisoning.