Resveratrol protects against cadmium-induced cerebrum toxicity through modifications of the cytochrome P450 enzyme system in microsomes.

Abstract

Cadmium (Cd), known as a vital contaminant in the environment, penetrates the blood-brain barrier and accumulates in the cerebrum. Acute toxicosis of Cd, which leads to lethal brain cerebral edema, intracellular accumulation and cellular dysfunction, remains to be illuminated with regard to the exact molecular mechanism of cerebral toxicity. Resveratrol (RES) existing in the edible portions of numerous plants is a simply acquirable and correspondingly less toxic natural compound with neuroprotective potential, which provides some theoretical bases for antagonizing Cd-induced cerebral toxicity. This work was executed to research the protective effects of RES against Cd-induced toxicity in chicken cerebrum. Markedly, these lesions were increased in the Cd group, which also exhibited a thinner cortex, reduced granule cells, vacuolar degeneration, and an enlarged medullary space in the cerebrum. Furthermore, Cd induced CYP450 enzyme metabolism disorders by interfering the nuclear xenobiotic receptor response (NXRs), enabling cerebrum to reduce the ability to metabolize exogenous substances, eventually leading to Cd accumulation. Meanwhile, accumulated Cd promotes the oxidative damage, and synergistically promote the damage of the neurons and glial cells. RES initiated the NXRs (especially for AHR and PXR), decreasing the expression of CYP450 genes, changing the content of CYP450, maintaining CYP450 enzyme normal activities, and exerting antagonistic action against the Cd-induced abnormal response of nuclear receptors. These results suggested that the cerebrum toxicity caused by Cd was reduced by pretreatment with RES. This article is protected by copyright. All rights reserved.