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BACKGROUND: 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 cerebral edema, intracellular accumulation and cellular dysfunction, remains to be illuminated with regard to the exact molecular mechanism of cerebral toxicity. Resveratrol (RES), present 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. RESULTS: 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 disrupting the nuclear xenobiotic receptor response (NXRs), enabling the cerebrum to reduce the ability to metabolize exogenous substances, eventually leading to Cd accumulation. Meanwhile, accumulated Cd promoted oxidative damage and synergistically promoted the damage to neurons and glial cells. CONCLUSION: RES initiated NXRs (especially for aromatic receptor and pregnancy alkane X receptor), 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 suggest that the cerebrum toxicity caused by Cd was reduced by pretreatment with RES. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) has been implicated in the pathogenesis of inflammation, myocardial infarction, angiocardiopathy, even cancers. However, it is unknown that Cd-induced cardiac toxicity through Nrf2-mediate antioxidant defense and Cytochrome P450 (CYP450) system. To ascertain the chemoprevention of Cd-induced cardiac toxicity, total 60 newborn chicks were fed with different doses of Cd (0 mg/kg, 35 mg/kg and 70 mg/kg) for a period of 90 days feed administration. Results indicated Cd exposure caused cardiac histopathology changed and functions abnormal, induced NOS activities raised and cardiac inflammation, triggering inflammation factors (IL-6, IL-8, TNF-α, and NF-κb) upregulation and inhabitation of IL-10. Cd caused increase of total CYP450 and Cytochrome b 5 (Cyt b 5) contents, while erythromycin N-demethylase (ERND), aminopyrin N-demethylase (APND), aniline-4-hydeoxylase (AH) and NADPH-cytochrome c reductase (NCR) indicated opposite situations with different degrees of reduction in microsomes. The mRNA level of most CYP450s isoforms (CYP1A1, CYP1A2, CYP1A5, CYP1B1, CYP2C18, CYP2C45, CYP3A4, CYP3A7 and CYP3A9) were significantly increase but CYP2D6 expression level changed not obvious. Furthermore, Cd treatment caused increased the peroxidation product (MDA) and H 2 O 2 over accumulation, the decreased of T-AOC accompanied by decreased activity of antioxidant enzymes (T-SOD, GST and GPX). Over accumulation of Cd lead to oxidative stress and activated Nrf2 signal pathway through upregulating pivotal target genes (HO-1, NQO1, GCLC, GCLM and SOD). These findings suggested Cd exposure caused cardiotoxicity through CYP450s enzymes homeostasis disturbance and Nrf2-mediated oxidative stress signal pathways defense. These results may provide new evidence on molecular mechanism of Cd-induced cardiac toxicity. Cadmium (Cd) enters the heart through cell membranes and disrupts the metabolic system. Findings from the present study provide new evidence that Cd exposure affects the modulation of Cytochrome P450 Systems and Nrf2 mediated antioxidant defense in the heart. Cd exposure resulted in oxidative stress via disrupting the homeostasis of CYP450s, activating Nrf2 signaling. All data supplied in the present study contribute to broadening knowledge on the mechanisms of Cd-induced cardiotoxicity. Image 1 • Cadmium exposure caused cardiotoxicity. • Cadmium induced cardiac inflammation. • Cadmium disturbed the Cytochrome P450 homeostasis in heart. • Cadmium induced oxidative stress via affecting Nrf2 mediated antioxidant defense. [ABSTRACT FROM AUTHOR]