| dc.description.abstract | Mercury (Hg) is a known environmental pollutant, especially methylmercury (MeHg) that is toxic during
the development of the central nervous system, which can lead to neuromotor impairment, depression,
insomnia and anxiety. Using the Drosophila melanogaster model, the effect of fruit fly exposure to MeHg
was assessed through the occurrence of neuromuscular (NM) and sleep-wake (SW) disorders present
in its progeny obtained by parental or preimaginal (before adult) exposure to this toxin. In parental
exposure, flies were exposed 24h to MeHg and transferred to lay eggs in normal medium (without
treatment). In preimaginal exposure, flies were exposed to MeHg 24h and only the eggs were kept in
the medium with treatment. Both protocols reduced fly viability and locomotor performance (LP),
although preimaginal exposure showed stronger impacts. Also, the preimaginal exposure disturbed the
flies’ circadian cycle (CC), showing a longer sleep duration and lower daily activity. Results corroborate
the hypothesis that low MeHg exposure could trigger subclinical symptoms related to a
neurotoxicological development effect. Thus, we evaluated whether guarana could show some
protective effect on neuro-oxy-inflammation of SH-SY5Y neural cells and on D. melanogaster
neurogenic toxicity (NM and SW patterns). From the previous results, the concentration of 9 μM MeHg
and guarana (1-20 mg/mL) was chosen with the combination of the two exposure protocols. It was
observed that guarana increased the viability and recovery of LP, especially in males, and reestablish a
normal CC patterns with the lowest guarana concentration. With cells exposed 72h to MeHg with a high
dose of MeHg (6 μM) combined with 100 μg/mL guarana, an attenuation of toxicity was observed. With
a sub-lethal concentration to evaluate the inflammatory activity of MeHg, the cells were exposed to 3
μM combined and 100 μg/mL guarana. The results showed a release reduction of pro-inflammatory
cytokines (IL-1β, IL-6, TNFα and IFNγ) and an increase of IL-10 (anti-inflammatory), yet guarana alone
was able to reduce IL-6 and INFα. The results together point to a neuroinflammatory effect of MeHg
toxicity, since neuroinflammation may be associated with depression and sleep disorders, found here.
Guarana showed an anti-inflammatory effect and improved the locomotor deficit and the SW pattern of
D. melonogaster. Based on the knowledge that the Amazonian riverine population is chronically exposed
to Hg from fish consumption and that in the municipality of Maués (AM) there is a highly longevity elderly
population that usually consumes guarana, we analyzed the potential protective effect of guarana
against Hg and the relationship with selenium (Se) in survival, motor neurotoxicity and general health
parameters in this population with and without habitual consumption of guarana (> 5 times per week).
The results showed an increase in survival in individuals who consume guarana habitually and are
exposed to high concentrations of Hg. Furthermore, low concentrations of Hg were associated with an
increase in the prevalence of systemic arterial hypertension (SAH), as well as high levels of Se and the
Se/Hg ratio. Low levels of Se were associated with higher prevalence of healthy volunteers, as well as
low levels of Se/Hg ratio. In addition, low levels of Se/Hg were associated with a higher incidence of
cardiovascular diseases. Hg levels were positively related to agility test and dynamic balance (TUG's
test) and negatively associated measures of limbs and waist circumference. The overall results suggest
a protective effect of guarana throughout life stages, since the initial development, seen in in vitro and
in vivo results, to a healthier senescence, seen in the elderly population chronically exposed to MeHg.
Additional studies are needed for a better understanding on the mechanisms of its toxicity and future
therapeutic strategies to protect chronically exposed populations. | |
