Prenatal exposure to organomercury, thimerosal, persistently impairs the serotonergic and dopaminergic systems in the rat brain: Implications for association with developmental disorders

Ida-Eto, Michiru; Oyabu, Akiko; Ohkawara, Takeshi; Tashiro, Yasura; Narita, Naoko; Narita, Minoru

doi:10.1016/j.braindev.2012.05.004

Cited by 19 publications

(10 citation statements)

References 19 publications

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“…Our results show for the first time that the thioredoxin system is also an important target for TM and EtHg. Moreover, neuroblastoma cells were quite sensitive to EtHg which stresses the toxic potential of TCV and other pharmaceutical formulas containing these compounds for the central nervous system (Ida-Eto et al 2013;Cinca et al 1980). …”

Section: Accepted Manuscriptmentioning

confidence: 98%

“…However, the mechanism of toxicity has not been well understood and studies with EtHg and TM are scarce in vivo and in vitro (Geir et al, 2009;Ida-Eto et al, 2013;Migdal et al, 2011;Mutkus et al, 2005;Pieper et al, 2014;Sharpe et al, 2012;Westphal et al, 2003). In this context, the better understanding of the molecular mechanism of action of TM and EtHg besides being a priority in toxicology research would help to clarify the epidemiological controversy around TCV and mercury intoxication.…”

Section: Introductionmentioning

confidence: 94%

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Toxicological effects of thiomersal and ethylmercury: Inhibition of the thioredoxin system and NADP+-dependent dehydrogenases of the pentose phosphate pathway

Rodrígues

Branco

et al. 2015

Toxicology and Applied Pharmacology

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Section: Accepted Manuscriptmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 94%

Toxicological effects of thiomersal and ethylmercury: Inhibition of the thioredoxin system and NADP+-dependent dehydrogenases of the pentose phosphate pathway

Rodrígues

Branco

et al. 2015

Toxicology and Applied Pharmacology

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“…Following TM administration on embryonic day 9, serotonin and dopamine was found to be significantly increased on postnatal day 50 in the hippocampus [132]. …”

Section: Research Evidencementioning

confidence: 99%

“…Two recent studies by Ida-Eto et al . [132,151] shows that prenatal TM exposure alters that the brain’s serotonin systems. Importantly, they found that TM administered to pregnant rats caused a dramatic increase in the number of serotonergic neurons in the brains in the TM group (1.9-fold increase, p < 0.01 compared to control).…”

Section: Research Evidencementioning

confidence: 99%

Thimerosal Exposure and the Role of Sulfation Chemistry and Thiol Availability in Autism

Kern

Haley

Geier

et al. 2013

IJERPH

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Autism spectrum disorder (ASD) is a neurological disorder in which a significant number of the children experience a developmental regression characterized by a loss of previously acquired skills and abilities. Typically reported are losses of verbal, nonverbal, and social abilities. Several recent studies suggest that children diagnosed with an ASD have abnormal sulfation chemistry, limited thiol availability, and decreased glutathione (GSH) reserve capacity, resulting in a compromised oxidation/reduction (redox) and detoxification capacity. Research indicates that the availability of thiols, particularly GSH, can influence the effects of thimerosal (TM) and other mercury (Hg) compounds. TM is an organomercurial compound (49.55% Hg by weight) that has been, and continues to be, used as a preservative in many childhood vaccines, particularly in developing countries. Thiol-modulating mechanisms affecting the cytotoxicity of TM have been identified. Importantly, the emergence of ASD symptoms post-6 months of age temporally follows the administration of many childhood vaccines. The purpose of the present critical review is provide mechanistic insight regarding how limited thiol availability, abnormal sulfation chemistry, and decreased GSH reserve capacity in children with an ASD could make them more susceptible to the toxic effects of TM routinely administered as part of mandated childhood immunization schedules.

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“…increase in hippocampal serotonin and dopamine in rat brain Ida-Eto M et al 35 In its 26 th meeting in Geneva, Switzerland, on 6-7 June 2012, the Global Advisory Committee on Vaccine Safety (GACVS) reviewed all the recently published studies and confirmed that the half life of ethylmercury in blood is 3-7 days. It also reviewed the quantitative risk assessment model used by FDA for cumulative toxicity of thimerosal in humans and concluded that the blood and brain ethyl mercury levels attained from cumulative vaccine doses do not reach toxic levels, as suggested by various animal and human studies, thus negating any relation between thimerosal exposure through vaccines and neurological toxicity.…”

mentioning

confidence: 98%

A review on thimerosal: an irreplaceable element of long-term immunisation strategy in low income countries

Singla

Gupta

Kaur

2017

Int J Basic Clin Pharmacol

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Thimerosal, an organic-mercury (Hg) compound containing 49.55% Hg by weight, is added to vaccines as a preservative permitting formulation of multi-dose vaccine vials. Being a derivative of ethylmercury, it has been linked with autism as a possible risk factor based on the assumption that exposure to ethylmercury would have similar neurotoxic effects as another mercurial compound, methylmercury. In 1999, AAP issued a joint statement emphasising the removal of thimerosal from vaccines. Subsequently, several studies have been conducted; those showing positive association between thimerosal exposure and autism have been recognised to be fraught with methodological flaws. On the other hand, many well controlled studies have failed to find any such causal relation and there are others that have clearly demonstrated a much favourable kinetic profile of ethylmercury as compared to methylmercury. Owing to the lack of data, AAP retired its original statement in 2002. Recently, thimerosal has been exempted from regulation by Minamata Convention on Mercury resulting in the continued use of low cost thimerosal containing vaccines in low income countries which cannot afford to run their immunisation program using single dose thimerosal free vaccines, that comparatively cost much higher, as is the case in high income countries. Some bodies view this as a discrimination on the basis of wealth of a nation and have opposed this decision. This review presents various studies regarding the causal association between thimerosal containing vaccines and autism. The current evidence fails to support any such association. Hence this review supports the exemption of thimerosal from regulation and also justifies its use in LICs for uninterrupted vaccination of the most vulnerable population.

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Prenatal exposure to organomercury, thimerosal, persistently impairs the serotonergic and dopaminergic systems in the rat brain: Implications for association with developmental disorders

Cited by 19 publications

References 19 publications

Toxicological effects of thiomersal and ethylmercury: Inhibition of the thioredoxin system and NADP+-dependent dehydrogenases of the pentose phosphate pathway

Toxicological effects of thiomersal and ethylmercury: Inhibition of the thioredoxin system and NADP+-dependent dehydrogenases of the pentose phosphate pathway

Thimerosal Exposure and the Role of Sulfation Chemistry and Thiol Availability in Autism

A review on thimerosal: an irreplaceable element of long-term immunisation strategy in low income countries

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