L-carnitine protects DNA oxidative damage induced by phenylalanine and its keto acid derivatives in neural cells: a possible pathomechanism and adjuvant therapy for brain injury in phenylketonuria

Increased cytokine levels induced by high phenylalanine concentrations in late diagnosis PKU patients compared to early diagnosis: Anti‐inflammatory effect of L‐carnitine

“…The mechanisms through which elevated Phe concentrations, the major amine acid accumulated in PKU, cause central nervous system injury continue to be a fertile field of investigation. 10,12,26 We also evaluated the L-car levels and verified that the PKU treated patients presented increased L-car levels when compared to control group and patients in the early and late diagnosis, showing that the L-car contained in the dietary formula was able to significantly increase levels in treated patients. We also found a significant inverse correlation between Phe concentrations versus L-car levels in phenylketonuric patients.…”

“…Another important role presented by L-car was attributed to its antioxidant activity against free radicals, aiding on the prevention to oxidative damage in various IEM. 12,13,41,42 In this sense, when evaluating a reliable biomarker of lipid peroxidation, formed by the peroxidation of arachidonic acid, our data demonstrate that PKU patients have significantly increased urinary 8-isoprostane levels at diagnosis as compared to the control group, and that L-car treatment was able to improve the isoprostane concentration, indicating a prevention of the lipid oxidation. These results are in accordance with previous study showing that treatment with L-car and selenium was able to reduce the thiobarbituric acid-reactive species, another parameter of lipid oxidative damage that reflects the amount of malondialdehyde (MDA) formation, an end product of membrane fatty acid peroxidation, in phenylketonuric treated patients (Sitta et al 43 ), reinforcing the antiperoxidative effects of L-carnitine.…”

“…47 Deon 11 and coworkers observed in phenylketonuric patients under treatment that urinary 8-OHdG, a product of DNA oxidative damage, were positively correlated with blood Phe levels and negatively correlated with blood L-car concentrations. Other studies carried out by our group have already shown that DNA damage through the alkaline comet assay that measures DNA strand breaks in single cells, 51 is induced by high Phe levels in whole blood cells from healthy individuals 10,52 and in C6 glial cells, 12 and that in vitro treatment with L-car reduced this damage. 10,12 These data enhance previous studies demonstrating antioxidant and free radical scavenger properties for L-car.…”

“…Other studies carried out by our group have already shown that DNA damage through the alkaline comet assay that measures DNA strand breaks in single cells, 51 is induced by high Phe levels in whole blood cells from healthy individuals 10,52 and in C6 glial cells, 12 and that in vitro treatment with L-car reduced this damage. 10,12 These data enhance previous studies demonstrating antioxidant and free radical scavenger properties for L-car. 53,54 In what concern to protein oxidation, we found no statistically significant difference in urinary di-tyrosine levels between controls and PKU patients.…”

“…9 L-car antioxidant and antiinflammatory properties have already been demonstrated in chronic and neurodegenerative diseases and also in inborn errors of metabolism (IEM), protecting cells from reactive oxygen species (ROS) and improving immunological functions. [10][11][12][13][14][15][16] It is known that the inflammatory response is closely related to antioxidant defenses and oxidative stress. Reactive oxygen/nitrogen species (ROS/RNS) are capable of altering different signaling pathways, stimulating the release of cytokines and other proinflammatory mediators.…”