Mercury Toxicity and Neurodegenerative Effects

Abstract

Mercury is among the most toxic heavy metals and has no known physiological role in humans. Three forms of mercury exist: elemental, inorganic and organic. Mercury has been used by man since ancient times. Among the earliest were the Chinese and Romans, who employed cinnabar (mercury sulfide) as a red dye in ink (Clarkson et al. 2007). Mercury has also been used to purify gold and silver minerals by forming amalgams. This is a hazardous practice, but is still widespread in Brazil's Amazon basin, in Laos and in Venezuela, where tens of thousands of miners are engaged in local mining activities to find and purify gold or silver. Mercury compounds were long used to treat syphilis and the element is still used as an antiseptic,as a medicinal preservative and as a fungicide. Dental amalgams, which contain about 50% mercury, have been used to repair dental caries in the U.S. since 1856.Mercury still exists in many common household products around the world.Examples are: thermometers, barometers, batteries, and light bulbs (Swain et al.2007). In small amounts, some organo mercury-compounds (e.g., ethylmercury tiosalicylate(thimerosal) and phenylmercury nitrate) are used as preservatives in some medicines and vaccines (Ballet al. 2001).Each mercury form has its own toxicity profile. Exposure to Hg0 vapor and MeHg produce symptoms in CNS, whereas, the kidney is the target organ when exposures to the mono- and di-valent salts of mercury (Hg+ and Hg++, respectively)occur. Chronic exposure to inorganic mercury produces stomatitis, erethism and tremors. Chronic MeHg exposure induced symptoms similar to those observed in ALS, such as the early onset of hind limb weakness (Johnson and Atchison 2009).Among the organic mercury compounds, MeHg is the most biologically available and toxic (Scheuhammer et a!. 2007). MeHg is neurotoxic, reaching high levels of accumulation in the CNS; it can impair physiological function by disrupting endocrine glands (Tan et a!. 2009).The most important mechanism by which mercury causes toxicity appears to bemitochondrial damage via depletion of GSH (Nicole et a!. 1998), coupled with binding to thiol groups ( -SH), which generates free radicals. Mercury has a high affinity for thiol groups ( -SH) and seleno groups ( -SeH) that are present in amino acids as cysteine and N-acetyl cysteine, lipoic acid, proteins, and enzymes. N-acetylcysteine and cysteine are precursors for the biosynthesis of GSH, which is among the most powerful intracellular antioxidants available to protect against oxidative stress and inflammation.Mercury and methylmercury induce mitochondrial dysfunction, which reduces ATP synthesis and increases lipid, protein and DNA peroxidation. The content of metallothioneines, GSH, selenium and fish high in omega-3 fatty acids appear to be strongly related with degree of inorganic and organic mercury toxicity, and with the protective detoxifying mechanisms in humans. In conclusion, depletion of GSH,breakage of mitochondria, increased lipid peroxidation, and oxidation of proteins and DNA in ...

Effects of genetic polymorphisms on antioxidant status and concentrations of the metals in the blood of riverside Amazonian communities co-exposed to Hg and Pb

“…Experimental studies suggest that MeHg and Pb exposure can lead to a decrease in levels of the antioxidant molecules, such as the tripeptide glutathione (GSH) and the activities of antioxidant enzymes like catalase (CAT), glutathione-peroxidase (GPx) and superoxide dismutase (SOD), which may result in oxidative damage in lipids, proteins and DNA (Barcelos et al, 2011a(Barcelos et al, , 2011bCarocci et al, 2014;Flora et al, 2012;Grotto et al, 2009).…”

Effects of Endocrine Disrupters on Immune Function and Inflammation

“…It concomitantly decreases glutathione levels, increasing the risk for inflammatory-driven oxidative damage in tissues [53].…”

Mercury Toxicity and Speciation Analysis

“…The binding to thiol groups of enzymes may result in conformational changes and thereby inhibition of their function. Catalytic, binding, and transport functions of proteins as well as DNA, RNA, and protein synthesis may also be affected [45,46]. Additionally, Hg species exert a strong affinity to selenols.…”