Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA

Abstract

Thimerosal generates ethylmercury in aqueous solution and is widely used as preservative. We have investigated the toxicology of Thimerosal in normal human astrocytes, paying particular attention to mitochondrial function and the generation of specific oxidants. We find that ethylmercury not only inhibits mitochondrial respiration leading to a drop in the steady state membrane potential, but also concurrent with these phenomena increases the formation of superoxide, hydrogen peroxide, and Fenton/Haber-Weiss generated hydroxyl radical. These oxidants increase the levels of cellular aldehyde/ketones. Additionally, we find a five-fold increase in the levels of oxidant damaged mitochondrial DNA bases and increases in the levels of mtDNA nicks and blunt-ended breaks. Highly damaged mitochondria are characterized by having very low membrane potentials, increased superoxide/hydrogen peroxide production, and extensively damaged mtDNA and proteins. These mitochondria appear to have undergone a permeability transition, an observation supported by the five-fold increase in Caspase-3 activity observed after Thimerosal treatment.

Toxicity of organic and inorganic mercury species in differentiated human neurons and human astrocytes

“…In a further study 14.4 J.LM thiomersal for one hour resulted in caspase-3 activation in normal human astrocytes (45). Thus, the induction of apoptosis as cell death mechanism seems to be dependent on the respective species of origin and cell type.…”

“…However, none of the compounds resulted in a caspase-3 activation in the astrocytes. Several studies have provided evidence before that organic and inorganic Hg species can induce apoptosis in different cell types [10,[43][44][45][46][47] ..…”

Vaccines against human diarrheal pathogens

“…91 Vaccine formulations may require preservatives such as thimerosal, a mercury-containing compound. 92 Other components can be amino acids and polysorbate for stabilization, formaldehyde and antibiotics for preventing bacterial growth and phenol and phenoxyethanol as preservatives. However, all these ingredients are often debated points.…”

Avaliação da distribuição, metabolismo e nefrotoxicidade do timerosal - um conservante a base de mercúrio usado em vacinas - utilizando modelos in vivo e in vitro

“…Até a data, a maioria dos estudos de avaliação de citotoxicidade promovida pelo EtHg/timerosal tem sido feita em células do tecido nervoso (BASKIN, et al, 2003;HUMPHREY, et al, 2005;SHARPE, et al, 2012). Isto é consequência dos intensos debates sobre a possível associação da exposição humana ao timerosal na vacinas e o desenvolvimento de autismo e outras desordens neurocomportamentais (BALL, et al, 2001;SHARPE, et al, 2012).…”

“…Isto é consequência dos intensos debates sobre a possível associação da exposição humana ao timerosal na vacinas e o desenvolvimento de autismo e outras desordens neurocomportamentais (BALL, et al, 2001;SHARPE, et al, 2012). Em contrapartida, o rim -um órgão-alvo da toxicidade do Hg foi raramente estudado quanto aos mecanismos de toxicidade e morte celular considerando a exposição ao EtHg/timerosal (CARNEIRO, et al, 2013).…”