Zebrafish as a Potential Model for Neurodegenerative Diseases: A Focus on Toxic Metals Implications.

In the last century, industrial activities increased and caused multiple health problems for humans and animals. At this moment, heavy metals are considered the most harmful substances for their effects on organisms and humans. The impact of these toxic metals, which have no biological role, poses a considerable threat and is associated with several health problems. Heavy metals can interfere with metabolic processes and can sometimes act as pseudo-elements. The zebrafish is an animal model progressively used to expose the toxic effects of diverse compounds and to find treatments for different devastating diseases that human beings are currently facing. This review aims to analyse and discuss the value of zebrafish as animal models used in neurological conditions, such as Alzheimer's disease (AD), and Parkinson's disease (PD), particularly in terms of the benefits of animal models and the limitations that exist.

Molecular Mechanisms of Cellular Injury and Role of Toxic Heavy Metals in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a progressive disease that affects millions of adults every year. Major risk factors include diabetes, hypertension, and obesity, which affect millions of adults worldwide. CKD is characterized by cellular injury followed by permanent loss of functional nephrons. As injured cells die and nephrons become sclerotic, remaining healthy nephrons attempt to compensate by undergoing various structural, molecular, and functional changes. While these changes are designed to maintain appropriate renal function, they may lead to additional cellular injury and progression of disease. As CKD progresses and filtration decreases, the ability to eliminate metabolic wastes and environmental toxicants declines. The inability to eliminate environmental toxicants such as arsenic, cadmium, and mercury may contribute to cellular injury and enhance the progression of CKD. The present review describes major molecular alterations that contribute to the pathogenesis of CKD and the effects of arsenic, cadmium, and mercury on the progression of CKD.

Susceptibility to Environmental Heavy Metal Toxicity among Americans with Kidney Disease.

Background: The consequences of low levels of environmental heavy metal exposure, as found widely in the United States, in those with impaired renal function remain underexplored. Methods: We examined the cross-sectional association of indices of renal function with lead and cadmium levels in blood and urine among National Health and Nutrition Examination Survey (NHANES) participants. We used the 1999-2002 cycle, which included measures of cystatin C, in order to quantify renal function most precisely and defined chronic kidney disease (CKD) as an estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2. Results: In weighted and adjusted analyses of 5638 participants, lead levels were 0.23 (95% CI, 0.03 to 0.42) µg/dl higher among participants with CKD, and 0.05 (95% CI, 0.01 to 0.09) µg/dL higher per 10 ml/min per 1.73 m2 lower eGFR. Cadmium levels were 0.02 (95% CI, 0.01 to 0.03) µg/L higher per 10 ml/min per 1.73 m2 lower eGFR. Black race significantly modified the association of lower eGFR with higher circulating lead levels (P interaction <0.001). A 10 ml/min per 1.73 m2 lower eGFR was associated with a 0.13 (95% CI, 0.06 to 0.21) µg/dl higher lead level among Black participants compared with 0.03 (95% CI, -0.04 to 0.11) µg/dl higher level among White participants. Among the 1852 participants with urinary metal measurements, despite higher circulating levels, those with CKD had significantly lower urinary lead levels (-0.16 [95% CI, -0.30 to -0.01] ng/ml) and urinary lead/creatinine ratios (-0.003 [95% CI, -0.004 to -0.001]). Conclusions: CKD is associated with higher blood lead levels, particularly among Blacks, and simultaneously, lower urinary lead levels, consistent with the hypothesis that CKD confers a state of heighted susceptibility to heavy metal environmental exposure by reducing its elimination. Given that low levels of exposure remain highly prevalent in the United States, further efforts to protect patients with CKD from heavy metal toxicity may be warranted.

Metal Profiles in Autism Spectrum Disorders: A Crosstalk between Toxic and Essential Metals.

Since hundreds of years ago, metals have been recognized as impacting our body's physiology. As a result, they have been studied as a potential cure for many ailments as well as a cause of acute or chronic poisoning. However, the link between aberrant metal levels and neuropsychiatric illnesses such as schizophrenia and neurodevelopmental disorders, such as autism spectrum disorders (ASDs), is a relatively new finding, despite some evident ASD-related consequences of shortage or excess of specific metals. In this review, we will summarize past and current results explaining the pathomechanisms of toxic metals at the cellular and molecular levels that are still not fully understood. While toxic metals may interfere with dozens of physiological processes concurrently, we will focus on ASD-relevant activity such as inflammation/immune activation, mitochondrial malfunction, increased oxidative stress, impairment of axonal myelination, and synapse formation and function. In particular, we will highlight the competition with essential metals that may explain why both the presence of certain toxic metals and the absence of certain essential metals have emerged as risk factors for ASD. Although often investigated separately, through the agonistic and antagonistic effects of metals, a common metal imbalance may result in relation to ASD.

Chronic Kidney Disease and Exposure to Nephrotoxic Metals.

Chronic kidney disease (CKD) is a common progressive disease that is typically characterized by the permanent loss of functional nephrons. As injured nephrons become sclerotic and die, the remaining healthy nephrons undergo numerous structural, molecular, and functional changes in an attempt to compensate for the loss of diseased nephrons. These compensatory changes enable the kidney to maintain fluid and solute homeostasis until approximately 75% of nephrons are lost. As CKD continues to progress, glomerular filtration rate decreases, and remaining nephrons are unable to effectively eliminate metabolic wastes and environmental toxicants from the body. This inability may enhance mortality and/or morbidity of an individual. Environmental toxicants of particular concern are arsenic, cadmium, lead, and mercury. Since these metals are present throughout the environment and exposure to one or more of these metals is unavoidable, it is important that the way in which these metals are handled by target organs in normal and disease states is understood completely.

Garimpo e mercúrio: impactos ambientais e saúde humana / Mining and mercury: environmental impacts and human health

A poluição provocada pelo mercúrio é um problema mundial relacionado às atividades de garimpo, com profundos impactos na saúde humana e no meio ambiente. Recentes avanços têm demonstrado uma relação causal entre a exposição ao mercúrio e diversas patologias humanas. O objetivo deste trabalho é discutir os efeitos do mercúrio como agente etiológico de patologias com base na literatura recente. A irreversibilidade dos danos ocasionados pela intoxicação por metais pesados alerta para a necessidade do segmento continuado e permanente destas populações. O desenvolvimento de novas metodologias, que permitam estabelecer uma relação causal, entre a intoxicação por metais pesados e o quadro epidemiológico presente na população exposta, deve ser implementado, estabelecendo as bases para avaliar a capacidade de resolução das medidas preventivas, corretivas e/ou mitigadoras.

The mercurial pollution is a worldwide problem related to gold mining activities with deep impacts on human and environmental health. Early advances have been showed a causal effect between mercury exposure and several human diseases. The objective of this paper is to discuss the effects of mercury as etiologic agent in several pathologies, based on recent literature data. The damage related to heavy metals intoxication alerts for the need of continuous monitoring of this kind of exposure. The development of new methodologies should be implemented searching the creation of a new background to evaluate the efficacy of preventive and corrective actions.