Abstract
Cadmium (Cd) is one of the most dangerous heavy metals that exists. A prolonged exposure to Cd causes toxic effects in a variety of tissues, including Central Nervous System (CNS), where it can penetrate the Blood Brain Barrier (BBB). Cd exposure has been linked to neurotoxicity and neurodegenerative diseases. Soy isoflavones have a strong antioxidant capacity, and they have been shown to have positive effects on cognitive function in females. However, the mechanisms underlying Cd neurotoxicity remain completely unresolved. The purpose of this study was to characterize the potential protective effect of a soy-based diet vs. a casein-based diet against Cd toxicity in rat cerebellum. Female Wistar rats were fed with casein (Cas) or soybean (So) as protein sources for 60 days. Simultaneously, half of the animals were administered either 15 ppm of Cadmium (CasCd and SoCd groups) in water or regular tap water as control (Cas and So groups). We analyzed Cd exposure effects on trace elements, oxidative stress, cell death markers, GFAP expression and the histoarchitecture of rat cerebellum. We found that Cd tissue content only augmented in the Cas intoxicated group. Zn, Cu, Mn and Se levels showed modifications among the different diets. Expression of Nrf-2 and the activities of CAT and GPx decreased in Cas and So intoxicated groups,while 3-NT expression increased only in the CasCd group. Morphometry analyses revealed alterations in the purkinje and granular cells morphology, decreased number of granular cells and reduced thickness of the granular layer in Cd-intoxicated rats, whereas no alterations were observed in animals under a So diet. In addition, mRNA expression of apoptotic markers BAX/Bcl-2 ratio and p53 expression increased only in the CasCd group, a finding confirmed by positive TUNEL staining in the cerebellum granule cell layer in the same group. Also, Cd intoxication elicited overexpression of GFAP by astrocytes, which was prevented by soy. White matter alterations were only subtle and characterized by intramyelinic edema in the CasCd group. Overall, these results unmask an irreversible toxic effect of a subchronic Cd intoxication on the cerebellum, and identify a protective role by a soy-based diet with potential as a therapeutic strategy for those individuals exposed to this dangerous environmental contaminant.
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Acknowledgements
The authors would like to thank Ricedal Alimentos S.A, Santa Fe, Argentina, for providing the soybean flour.
Funding
The present study was supported by grants from Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and Universidad Nacional de San Luis (UNSL), Argentina (PROICO 2–418). Dr Pablo Lopez was funded by a grant from Secyt-National University of Córdoba.
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Supplementary file1 A mid-sagittal section of the cerebellum of a control rat. The measurements were performed on the midsagittal section of the cerebellum. 1) Cortical thickness at fissure base 2) Cortical thickness facing at fissure, 3) Cortical thickness at folium surface, ML) Molecular layer, GL) Granular layer, *: Cerebellar medulla, cresyl violet staining. (TIF 170 kb)
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Martin Molinero, G.D., Boldrini, G.G., Pérez Chaca, M.V. et al. A soybean based-diet prevents Cadmium access to rat cerebellum, maintaining trace elements homeostasis and avoiding morphological alterations. Biometals 36, 67–96 (2023). https://doi.org/10.1007/s10534-022-00462-w
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DOI: https://doi.org/10.1007/s10534-022-00462-w