Abstract
Background: Benzophenone-3 (2-Hydroxy-4-methoxy-benzophenone, oxybenzone, BP-3) is a commonly used ultraviolet filter added to cosmetics and to plastic based packing materials. BP-3 is absorbed through the skin and to a lesser extent it enters the organism through digestive system. After topical application of the ointment containing 5% BP-3, the maximum concentration of this compound in the human serum reached 200-300 micro;g/L and after 24 hours following application it amounted 80-200 microg/L. As a lipophilic compound BP-3 accumulates in organs, mainly in liver, kidneys, spleen and testicles. BP-3 crosses the blood-placenta barrier and thus may directly affect the fetus. Also, BP-3 disrupts the hormonal balance, mainly due to its action on the steroid hormone receptors. Recently, it has been discovered, that BP-3 also shows neurotoxicity, however, the possible mechanism of this action remains unclear.
Methods: The purpose of this study was to determine, whether prenatal, followed by adulthood exposure to BP-3, would cause pathological changes in the frontal cortex and hippocampus; i.e. brain structures predominantly sensitive to damage. Sprague-Dawley female rats received BP-3 topically in a dose 100 mg/kg, twice a day, during the pregnancy. The offspring (males) were analogically exposed to BP-3, during the 7th and 8th week of life. Animals were killed by rapid decapitation, brain regions (hippocampus and frontal cortex) were dissected for Western blot analysis and the concentration of glutamate was determined in microdialysates by LC-MS method.
Results: Exposure to BP-3 significantly increased extracellular level of glutamate, detected in microdialysates of the frontal cortex and hippocampus. Protein expression of the GLT-1 was significantly lowered and xc- increased in both frontal cortex and hippocampus of animals that received BP-3. GLT-1 activity consists of the uptake of the extracellular glutamate to astrocytes and xc- conversely releases glutamate to the extracellular space, thus the obtained Western blot results correspond with changes in glutamate levels found in microdialysates of experimental animals.
Conclusion: The obtained results showed, that exposure to BP-3 has neurotoxic effects associated with increased glutamate release, probably due to the disturbances in the GLT-1 and xc- expressions.
This study was supported by the National Science Centre (Poland) Grant No. 2014/15/B/NZ7/00892
