Protective role of alpha-lipoic acid in impairments of social and stereotyped behaviors induced by early postnatal administration of thimerosal in male rat

Neurotoxicol Teratol. 2018 May-Jun;67:1-9. doi: 10.1016/ Epub 2018 Feb 24.


Aim Thimerosal, a mercury-containing preservative has been widely used in a number of biological and drug products, including many vaccines, and has been studied as a possible etiological factor for some neurodevelopmental disabilities. Here, the protective effects of Alpha Lipoic Acid (ALA), an organosulfur compound derived from Octanoic Acid, on Thimerosal-induced behavioral abnormalities in rat were examined.

Methods: 108 male Wistar rats were divided into three cohorts and treated as follows: 1) Thimerosal at different doses (30, 300, or 3000 μg Hg/kg) in four i.m. injections on 7, 9, 11, 15postnatal days. 2) ALA (at doses of 5, 10 and 20 mg/kg), following the same order; 3) single dose of Thimerosal (3000 μg Hg/kg) plus ALA at different doses (5, 10 or 20 mg/kg), by the previously described method. A saline treated control group and a ALA vehicle control (0.1% NaOH) were also included. At 5 and 8 weeks after birth, rats were evaluated with behavioral tests, to assess locomotor activity, social interactions and stereotyped behaviors, respectively.

Results: The data showed that Thimerosal at all doses (30, 300 and 3000 μg Hg/kg) significantly impacted locomotor activity. Thimerosal at doses of 300 and 3000 but not 30 μg Hg/kg impaired social and stereotyped behaviors. In contrast, ALA (at doses of 5, 10 and 20 mg/kg) did not alter behaviors by itself, at doses of 20 mg/kg, it reduced social interaction deficits induced by the highest dose of Thimerosal (3000 μg Hg/kg). Moreover, ALA, at all doses prevented the adverse effects of Thimerosal on stereotyped behaviors.

Conclusions: the results of this preclinical study, consistent with previous studies on mice and rats, reveals that neonatal dose-dependent exposure to Thimerosal mimicking the childhood vaccine schedule can induce abnormal social interactions and stereotyped behaviors similar to those observed in neurodevelopmental disorders such as autism, and, for the first time, revealed that these abnormalities may be ameliorated by ALA. This indicates that ALA may protect against mercurial-induced abnormal behaviors.

Keywords: Alpha lipoic acid; Development; Postnatal exposure; Preclinical model; Thimerosal.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Locomotion / drug effects
  • Male
  • Protective Agents / pharmacology
  • Rats
  • Social Behavior*
  • Stereotyped Behavior / drug effects*
  • Thimerosal / adverse effects
  • Thimerosal / antagonists & inhibitors*
  • Thioctic Acid / pharmacology*


  • Protective Agents
  • Thimerosal
  • Thioctic Acid