l-Tyrosine Induces DNA Damage in Brain and Blood of Rats

Abstract

Mutations in the tyrosine aminotransferase gene have been identified to cause tyrosinemia type II which is inherited in an autosomal recessive manner. Studies have demonstrated that an excessive production of ROS can lead to reactions with macromolecules, such as DNA, lipids, and proteins. Considering that the L-tyrosine may promote oxidative stress, the main objective of this study was to investigate the in vivo effects of L-tyrosine on DNA damage determined by the alkaline comet assay, in brain and blood of rats. In our acute protocol, Wistar rats (30 days old) were killed 1 h after a single intraperitoneal L-tyrosine injection (500 mg/kg) or saline. For chronic administration, the animals received two subcutaneous injections of L-tyrosine (500 mg/kg, 12-h intervals) or saline administered for 24 days starting at postnatal day (PD) 7 (last injection at PD 31), 12 h after the last injection, the animals were killed by decapitation. We observed that acute administration of L-tyrosine increased DNA damage frequency and damage index in cerebral cortex and blood when compared to control group. Moreover, we observed that chronic administration of L-tyrosine increased DNA damage frequency and damage index in hippocampus, striatum, cerebral cortex and blood when compared to control group. In conclusion, the present work demonstrated that DNA damage can be encountered in brain from animal models of hypertyrosinemia, DNA alterations may represent a further means to explain neurological dysfunction in this inherited metabolic disorder and to reinforce the role of oxidative stress in the pathophysiology of tyrosinemia type II.

Macroevolutionary patterns in overexpression of tyrosine: An anti‐herbivore defence in a speciose tropical tree genus, Inga (Fabaceae)

“…Although the effects of overexpression of primary metabolites on herbivores are poorly studied, we propose several lines of argument suggesting that the high concentrations of L‐tyrosine seen in Inga (5%–20%) likely are functioning as a defence against the majority of herbivores. First, as outlined in the introduction, feeding trials with insects and mammals show toxic or lethal effects (De Prá et al, ; Hazel et al, ; Lokvam et al, ; Rehr et al, ; Sterkel et al, ). Second, if tyrosine was generally nutritive/attractive to herbivores, this mutation would quickly have been eliminated.…”

“…High haemolymph tyrosine has been implicated in increased fluid secretion from the Malpighian tubules of both Rhodnius (Hemiptera) and Drosophila (Hazel, Ianowski, Christensen, Maddrell, & O'Donnell, ), potentially disrupting an insect's water balance. In rats, tyrosine causes oxidative stress leading to damage of DNA, lipids and proteins (De Prá et al, ). DOPA, a derivative of tyrosine found in some Inga species, caused severe cuticular deformities for a lepidopteran herbivore ( Spodoptera ) with the addition of only 0.25% dry mass to artificial diets (Rehr, Janzen, & Feeney, ).…”

Selenium reduces bradykinesia and DNA damage in a rat model of Parkinson's disease

“…If any of the treatments had induced apoptosis at levels that could influence the findings related to the classes of damage, this difference should have been noted in the number of ghost comets. Perhaps the use of other substances caused differences that were detectable by this technique [46]. Thus, we do not discourage the use of the comet assay when evaluating the effect of different Se compounds on DNA damage in samples from central nervous system tissue.…”

Tyrosinemia Type Iii: A Case Report of Siblings and Literature Review

“…Several studies revealed that hypertyrosinemia inhibits the functioning of respiratory chain complexes, compromises the Krebs cycle, and decreases creatine kinase and pyruvate kinase activities, inducing an oxidative stress status and an impairment of energy metabolism in the cerebral cortex of rats. [5][6][7][8] Patients detected by newborn screening appear to have fewer neurological symptoms and a lower degree of cognitive impairment compared to those diagnosed later in life. [2][3] However, it is unclear if the clinical outcome is determined by the decrease in plasma tyrosine levels, and the neurological evolution can vary despite similar tyrosine levels.…”