An overview on amyotrophic lateral sclerosis and cadmium.

The present review represents an update about the knowledge of the possible role of Cadmium (Cd) in amyotrophic lateral sclerosis (ALS) initiation and its progression. ALS is a neurodegenerative disease that occurs in adulthood; its etiology is unknown and leads to death within a few years from its appearance. Among the various possible causes that can favor the development of the disease, heavy metals cannot be excluded. Cadmium is a heavy metal that does not play a biological role, but its neurotoxicity is well known. Numerous in vitro studies on cell and animal models confirm the toxicity of the metal on the nervous system, but these data are not accompanied by an epidemiological evidence, and, thus, an unclear correlation between Cd and the onset of the disease can be pointed out. On the other hand, a possible multifactorial and synergic mechanism in which Cd may have a role can explain the ALS onset. More efforts in new clinical, biochemical, and epidemiological studies are necessary to better elucidate the involvement of Cd in this lethal disease.

Amyotrophic lateral sclerosis and lead: A systematic update.

Heavy metals are considered to be among the leading environmental factors that trigger amyotrophic lateral sclerosis (ALS). However, no convincing biopathological mechanism and therapeutic clinical implication of such metals in ALS pathogenesis have been established. This is partly attributable to the technical and scientific difficulties in demonstrating a direct and causative role of heavy metals in the onset of ALS in patients. However, a body of epidemiological, clinical and experimental evidences suggest that lead (Pb), more than other metals, could actually play a major role in the onset and progression of ALS. Here, to clarify the nature of the association and the causative role of Pb in ALS, we comprehensively reviewed the scientific literature of the last decade with objective database searches and the methods typically adopted in systematic reviews, critically analysing and summarising the various scientifically sound evidence on the relationship between ALS and Pb. From these tasks, we noted a number of multidisciplinary associations between ALS and Pb, and specifically the importance of occupational exposure to Pb in ALS development and/or progression. We also report the possible involvement of TAR DNA binding protein (TDP-43)-based molecular mechanism in Pb-mediated ALS, although these data rely on a single study, which included both in vitro experiments and an animal model, and are therefore still preliminary. Finally, we briefly examined whether this knowledge could inspire new targeted therapies and policies in the fight against ALS.

Trace elements in ALS patients and their relationships with clinical severity.

An exploratory study of trace elements in ALS and their relationships with clinical severity was detected. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that causes irreversible damage in humans, with the consequent loss of function of motoneurons (MNs), with a prognosis up to 5 years after diagnosis. Except to genetic rare cases it is not known the etiology of the disorder. Aim of our research is to investigate the possible role of heavy metals in the severity of the disease. In this study, by the use of plasma mass (ICP-MS), we have analyzed the content of essential and heavy metals such: Pb, Cd, Al, Hg, Mn, Fe, Cu, Zn, Se, Mg, and Ca, in blood, urine and hair of ALS patients and controls; moreover we divided the patients in two groups for disease severity and analyzed the difference among the groups, in order to study a possible involvement of metals in the severity of the damage. Our results suggest a protective role of Selenium, involved in protective antioxidant mechanisms, and a risk factor in the case of presence of Lead in blood. The levels of the other metals are not easy to interpret, because these may be due to life style and for essential metals a consequence of the disease condition, not a cause.

Essential trace elements in amyotrophic lateral sclerosis (ALS): Results in a population of a risk area of Italy.

Sardinian (Italy) island population has a uniquely high incidence of amyotrophic lateral sclerosis (ALS). Essential trace element levels in blood, hair, and urine of ALS Sardinian patients were investigated in search of valid biomarkers to recognize and predict ALS. Six elements (Ca, Cu, Fe, Mg, Se, and Zn) were measured in 34 patients compared to 30 age- and sex-matched healthy controls by a validated method. Levels of Ca and Cu in blood and of Se and Zn in hair were significantly higher in ALS than in controls, while urinary excretion of Mg and Se was significantly decreased. The selected cut-off concentrations for these biomarkers may distinguish patients with or without ALS with sufficient sensitivity and specificity. Many positive (as Se-Cu and Se-Zn) and negative associations (as Ca-Mg and Ca-Zn) between elements suggested that multiple metals involved in multiple mechanisms have a role in the ALS degeneration.

Level of neurotoxic metals in amyotrophic lateral sclerosis: A population-based case-control study.

The association between exposure to toxic metals and amyotrophic lateral sclerosis (ALS) was explored in a population-based case-control study in the Sardinia island (Italy), a region characterized by elevated rates of ALS cases. In 34 patients with ALS (mean age, 62 ± 10 years) and 30 controls (mean age, 65 ± 11 years), Al, Cd, Hg, Mn and Pb were determined in blood, hair and urine by sector field inductively coupled mass spectrometry. Results indicated that, in blood, concentrations of Al (p=0.045) and Pb were higher (p=0.026) in ALS patients than in control subjects. In hair, a depletion of Al (p=0.006) and Mn (p=0.032) concentrations in ALS subjects respect to controls was found. In urine, no significant differences between cases and controls were observed. Thus, some metals seemed to be associated with ALS degeneration, but a definitive conclusion is still far considering the multiple risk factors (genetic mutations, environmental toxicants and stressors) involved in the disease. Finally, the interpretation that deregulated metal concentrations can be a consequence of the degenerative process, rather than a cause, is also valid.

Blood metals concentration in type 1 and type 2 diabetics.

Mechanisms for the onset of diabetes and the development of diabetic complications remain under extensive investigations. One of these mechanisms is abnormal homeostasis of metals, as either deficiency or excess of metals, can contribute to certain diabetic outcomes. Therefore, this paper will report the blood levels of chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), mercury (Hg), nickel (Ni), lead (Pb), selenium (Se), and zinc (Zn) in subjects with type 1 diabetes (n = 192, mean age 48.8 years, mean disease duration 20.6 years), type 2 diabetes (n = 68, mean age 68.4 years, mean disease duration 10.2 years), and in control subjects (n = 59, mean age 57.2 years), and discuss the results indicating their possible role in diabetes. The metal concentrations were measured by sector field inductively coupled plasma mass spectrometry after microwave-induced acid digestion of blood samples. The accuracy was checked using a blood-based certified reference material, and recoveries of all elements were in the range of 92-101 % of certified values. Type 1 diabetes was found to be associated with Cr (p = 0.02), Mn (p < 0.001), Ni (p < 0.001), Pb (p = 0.02), and Zn (p < 0.001) deficiency, and type 2 diabetes with Cr (p = 0.014), Mn (p < 0.001), and Ni (p < 0.001) deficiency. These deficiencies were appreciated also subdividing the understudied patients for gender and age groups. Furthermore, in type 1 diabetes, there was a positive correlation between Pb and age (p < 0.001, ρ = 0.400) and Pb and BMI (p < 0.001, ρ = 0.309), while a negative correlation between Fe and age (p = 0.002, ρ = -0.218). In type 2 diabetes, there was a negative correlation between Fe and age (p = 0.017, ρ = -0.294) and Fe and BMI (p = 0.026, ρ = -0.301). Thus, these elements may play a role in both forms of diabetes and combined mineral supplementations could have beneficial effects.