Hippocampus is the brain area where aluminum (Al) accumulates in abundance and is widely associated with learning and memory. In the present study, we evaluate behavioral, tissue, and proteomic changes in the hippocampus of Wistar rats caused by exposure to doses that mimic human consumption of aluminum chloride (AlCl₃) in urban areas. For this, male Wistar rats were divided into two groups: Control (distilled water) and AlCl₃ (8.3 mg/kg/day), both groups were exposed orally for 60 days. After the Al exposure protocol, cognitive functions were assessed by the Water maze test, followed by a collection for analysis of the global proteomic profile of the hippocampus by mass spectrometry. Aside from proteomic analysis, we performed a histological analysis of the hippocampus, to the determination of cell body density by cresyl violet staining in Cornu Ammonis fields (CA) 1 and 3, and hilus regions. Our results indicated that exposure to low doses of aluminum chloride triggered a decreased cognitive performance in learning and memory, being associated with the deregulation of proteins expression, mainly those related to the regulation of the cytoskeleton, cellular metabolism, mitochondrial activity, redox regulation, nervous system regulation, and synaptic signaling, reduced cell body density in CA1, CA3, and hilus.

This study evaluated the cardiopulmonary protective effects of essential elements (Zn and Se) against heavy metals mixture (HMM) exposure. Twenty five female Sprague Dawley albino rats, divided in to five groups: controls were orally treated only with distilled water; next, group 2 was exposed to HMM with the following concentrations: 20 mg/kg of Pb body weight, 0.40 mg/kg of Hg, 0.56 mg/kg of Mn, and 35 mg/kg of Al. Groups 3, 4 and 5 were exposed to HMM and co-treated with zinc chloride (ZnCl₂; 0.80 mg/kg), sodium selenite (Na₂SeO₃;1.50 mg/kg) and both zinc chloride and sodium selenite, respectively. The experiment lasted for 60 days. Afterwards animals were sacrificed, and we conduced biochemical and histopathological examination of the heart and lungs. HMM only exposed animals had an increased levels of malondialdehyde (MDA) and nitric oxide (NO), increased IL-6 and TNF-α, attenuated SOD, GPx, CAT and GSH and caspase 3 in the heart and lungs. HMM affected NF-kB and Nrf2 in the heart muscle with histomorphological alterations. Zn and Se attenuated adverse effects of HMM exposure. Essential element supplementation ameliorated heavy metal cardiopulmonary intoxication in rats. Schematic approach to experimental design (used heavy metals mixture and duration of exposure), examined organs and main outcomes of this study.

Heavy metals could exert a strong cardiotoxic effect, since cardiomyocytes are vulnerable cells in general, very sensitive to heavy metals-induced toxicity. The correlation between exposure to heavy metals and their contribution to the pathophysiology of diverse cardiovascular disorders, such as coronary artery disease (CAD) and cardiomyopathies (CMPs), has gained recognition primarily through clinical investigations wherein metal(loid) levels were quantified in the blood or urine of individuals afflicted with aforementioned disorders. However, a crucial perspective is absent due to lack of studies that investigate the accumulation of heavy metals within cardiac tissue. These studies, whether post-mortem or involving heart samples obtained during invasive procedures, are currently lacking. To achieve a comprehensive understanding of the potential involvement of metal(loid)s in the genesis of e.g. CMPs or CAD, these inquiries are indispensable. Furthermore, certain comorbidities like iron deficiency may expedite the bioaccumulation of myocardial heavy metals by augmenting the density of transferrin receptor 1 (TfR1). The impact of heavy metals on the heart's contractile machinery, coupled with their potential to initiate mitochondrial apoptosis through triggered pathways, forms part of the intricate pathophysiological landscape. Central to these mechanisms is the generation of reactive oxygen species (ROS) and the peroxidation of macromolecules. This review highlights the research findings on the bioaccumulation of heavy metals within the myocardium and elucidates the molecular mechanisms through which metal(loid) s induce cardiotoxicity