English abstract
Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental
disorder among both children and adults. Recently, antioxidant-therapies have gained a
lot of attention among scientists working on ADHD. Accordingly, the present study
aimed at investigating the potential neuroprotective roles of gallic acid (GA) and ellagic
acid (EA) in a trimethyltin chloride (TMT)-induced animal model, which is a wellknown model for ADHD. In so doing, 80 pregnant Wistar rats were divided into eight
groups, including control (saline only), sham (9mg/kg TMT+saline), GA (50, 100 and
200 mg/kg GA+ 9 mg/kg TMT respectively) and EA (10, 25 and 50 mg/kg EA+ 9
mg/kg TMT respectively). All TMT injections, as well as GA and EA, gavages were
done on gestational days (GDs) 12 to 14 and GDs16 to 18, as these days are known to
be crucial in the brain development of the embryos. To find out the effect of these
antioxidants on the animals' behavior, four behavioral tests were conducted including
elevated-plus maze, open field test, T-maze, and five-choice serial reaction time task.
Findings of the behavioral studies showed statistically significant differences among
the sham and treatment groups in terms of inattention, hyperactivity, and impulsivity,
which suggested that GA and EA would be useful in the prevention of ADHD. These
differences were observed either in all or in some dosages of EA and GA. The molecular
biology study mainly focused on five important genes involved in the onset of ADHD,
namely 5HT2A, Dat1, SLC6A2, DRD4, and DRD5. Our results revealed that EA and
GA upregulated the expression of these genes, either in all or in some dosages. Further,
the biochemical parameters were analyzed to find out the effects of GA and EA in a
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TMT-induced ADHD model. These included brain-derived neurotrophic factor
(BDNF), nitric oxide, 4-hydroxynonenal, paraoxonase1, and total antioxidant capacity.
The present study indicated that these parameters were altered significantly among the
sham and treatment groups, either in all or in some dosages of EA and GA. Finally, the
histopathological results were presented and the brain changes during the study were
discussed through transmission electron microscopy and light microscopy. This study
is congruent with the emerging literature suggesting that antioxidants have the potential
to impact the symptoms of ADHD. Therefore, certain dosages of EA and GA were
suggested to be used as alternatives to medical therapies. However, there is still a need
for extensive research to find out the beneficial effects of these antioxidants on ADHD.
