A soybean based-diet prevents Cadmium access to rat cerebellum, maintaining trace elements homeostasis and avoiding morphological alterations.

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.

Diazepam Impairs Innate and Adaptive Immune Responses and Ameliorates Experimental Autoimmune Encephalomyelitis.

Currently there is increasing attention on the modulatory effects of benzodiazepines on the immune system. Here, we evaluate how Diazepam (DZ) affects both innate and adaptive immunity. We observed that treatment with DZ and Lipopolysaccharide (LPS) on macrophages or dendritic cells (DCs) induced a defective secretion of IL-12, TNF-α, IL-6 and a lesser expression of classical activation markers as NO production and CD40 in comparison with LPS condition. More importantly, mice pre-treated with DZ and then challenged to LPS induced-septic shock showed reduced death. The DZ treatment shifted the LPS-induced pro-inflammatory cytokine production of peritoneal cells (PCs) to an anti-inflammatory profile commanded by IL-10. In agreement with this, DZ treatment prevented LPS-induced DC ability to initiate allogeneic Th1 and Th17 responses in vitro when compared with LPS-matured DC. Since these inflammatory responses are the key in the development of the experimental autoimmune encephalomyelitis (EAE), we treated EAE mice preventively with DZ. Mice that received DZ showed amelioration of clinical signs and immunological parameters of the disease. Additionally, DZ reduced the release of IFN-γ and IL-17 by splenocytes from untreated sick mice in vitro. For this reason, we decided to treat diseased mice therapeutically with DZ when they reached the clinical score of 1. Most importantly, this treatment ameliorated clinical signs, reduced the MOG-specific inflammatory cytokine production and prevented axonal damage. Altogether, these results indicate that DZ is a potent immunomodulator capable of controlling undesired innate and adaptive immune responses, both at the beginning of these responses and also once they have started.