Title : The neuroprotective effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline against perinatal exposure of fluorine
Background: Human population living in urban environment is exposed to excessive levels of toxins, such as fluorine (F). Fluorine present in excess, e.g. in water or soil have a strong impact on living organisms. Passing through the blood-brain barrier, it damage the central nervous system (CNS). It is especially dangerous for young animals and children, because in these organisms the blood-brain barrier is still not mature. 1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous compound, which exhibits the neuroprotective, antidepressant-like effect and MAO-inhibiting properties.
Methodology: The aim of the present study was to investigated the impact of acute and chronic (once during 14 days) treatment of 1MeTIQ (50 mg/kg i.p.) on the disturbances in dopamine metabolism and release evoked by perinatal exposure of fluorine. The fluorine (NaF) model involves the administration of sodium fluoride in drinking water to pregnant rats and born pups till 1 month of age i.e. to sexual maturity. We performed both ex vivo and in vivo microdialysis study. The dopamine and its metabolites were assayed in dialysates or in the tissue using HPLC with ED.
Results: The present ex vivo study showed that perinatal exposure to fluorine caused not significant increase the concentration of DOPAC and HVA in the frontal cortex and this effect was completely inhibited by chronic treatment with 1MeTIQ. Additionally, fluorine induced decrease of NA and 5-HT concentration in the nucleus accumbens and this effect was also reversed by chronic 1MeTIQ administration. Moreover, the in vivo microdialysis study indicated that exposure to fluorine induced significant elevation in DOPAC and HVA concentration in the extracellular space. This toxic effect was completely blocked by chronic treatment with 1MeTIQ.
Conclusions: 1MeTIQ has shown the neuroprotective activity in animal model of fluorine poisoning. The mechanism responsible for the neuroprotection of 1MeTIQ against fluorine toxicity may be connected with the antagonism to fluorine-induced oxidative stress and reduction of free radicals production in the rat brain structures.