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Phenylketonuria (PKU) is a disease caused by a deficiency of phenylalanine hydroxylase (PAH), resulting in an accumulation of phenylalanine (Phe) in the brain tissue, cerebrospinal fluid, and other tissues of PKU patients. Considering that high levels of Phe are associated with neurological dysfunction and that the mechanisms underlying the neurotoxicity in PKU remain poorly understood, the main objective of this study was to investigate the in vivo and in vitro effects of Phe on DNA damage, as determined by the alkaline comet assay. The results showed that, compared to control group, the levels of DNA migration were significantly greater after acute administration of Phe, p- chlorophenylalanine (p-Cl-Phe, an inhibitor of PAH), or a combination thereof in cerebral cortex and blood, indicating DNA damage. These treatments also provoked increase of carbonyl content. Additionally, when Phe or p-Cl-Phe was present in the incubation medium, we observed an increase in the frequency and index of DNA damage in the cerebral cortex and blood, without affecting lactate dehydrogenase (LDH) release. Our in vitro and in vivo findings indicate that DNA damage occurs in the cerebral cortex and blood of rats receiving Phe, suggesting that this mechanism could be, at least in part, responsible for the neurological dysfunction in PKU patients. Key words: phenylketonuria, phenylalanine, DNA damage, comet assay, oxidative stress. La phenylcetonurie (PCU) est une la maladie causee par une deficience en phenylalanine hydroxylase (PAH) qui resulte en une accumulation de phenylalanine (Phe) dans le tissu cerebral, le liquide cephalorachidien et dans d'autres tissus chez les patients qui en sont atteints. Puisque des niveaux eleves de Phe sont associes a une dysfonction neurologique et que les mecanismes qui sous-tendent la neurotoxicite dans la PCU demeurent peu compris, l'objectif principal de cette etude etait d'examiner les effets de la Phe sur le dommage a l'ADN in vivo et in vitro, en utilisant la version alcaline du dosage COMET. Les resultats ont montre que, comparativement au groupe controle, les niveaux de migration d'ADN etaient significativement superieurs dans le cortex cerebral et le sang apres une administration aigue de Phe, de p-chlorophenylalanine (p-Cl-Phe, un inhibiteur de la PAH) ou d'une combinaison des deux, indiquant la presence de dommages a l'ADN. Ces traitements provoquaient aussi une augmentation du contenu en carbonyles. De plus, lorsque la Phe ou la p-Cl-Phe etaient presentes dans le milieu d'incubation, une augmentation de la frequence et de l'indice du dommage a l'ADN etait observee dans le cortex cerebral et lesang, sans que la liberation de lactate deshydrogenase (LDH) ne soit affectee. Les resultats actuels des experiences realisees in vivo et in vitro indiquent qu'un dommage a l'ADN survient dans le cortex cerebral et le sang des rats ayant recu de la Phe, ce qui suggere que ce mecanisme pourrait etre, au moins en partie, responsable de la dysfonction neurologique observee chez les patients atteints de PCU. [Traduit par la Redaction] Mots-cles: phenylcetonurie, phenylalanine, dommage a l'ADN, dosage COMET, stress oxidant., Introduction PKU (Online Mendelian Inheritance in Man (OMIM) Nos. 261600 and 261630) is a metabolic disorder caused by a PAH (EC 1.14.16.1) deficiency, resulting in an accumulation of its upstream [...]

ObjectiveThis study investigated the influence of ageing – in particular the decrease of gonadal hormone levels during the ageing process – on the memory and the levels of DNA damage in the hippocampus of female rats.MethodsThree groups of female Wistar rats were investigated: Group I consisted of non-ovariectomised, adult animals (6 months old); Group II consisted of non-ovariectomised, aged animals (18 months old); and Group III consisted of ovariectomised, aged animals (18 months old). The memory of the animals in these groups was examined via novel object recognition and inhibitory avoidance tests. The hippocampus tissue samples of all animals were obtained via biopsy and used to quantify the DNA damage using a Comet Assay.ResultsAccording to our findings, the process of ageing results in a change during the behavioural tests. To prevent genotoxic damage to the hippocampus caused by the ageing process, lowered hormone levels seem to be part of a protective biochemical mechanism in the body of rats. Animals that were previously submitted to an ovariectomy adapted better to these lower levels of hormones.ConclusionOur results indicate that ovariectomy can provide beneficial long-term effects on the memory. However, this could be specific to the kind of memory examined, as the aversive memory deficits caused by ageing were not affected by ovariectomy. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Objetive: The aim of this study was to evaluate the effects of diphenyl diselenide (PhSe)2 and ebselen (EB) in ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in rats., Methods: The effects of (PhSe)2 and EB in rats submitted to DSS-induced colitis were determined by measurement of oxidative stress parameters, inflammatory response and bowel histopathological alterations., Results: Animals developed moderate to severe neutrophil infiltration in histopathology assay in DSS rats and (PhSe)2 improved this response. Moreover, the treatment with (PhSe)2 decreased the oxidative damage in lipids and proteins, as well as reversed the superoxide dismutase (SOD) and catalase (CAT) levels in rats treated with DSS. EB was able only to reverse damage in lipids and the low levels of SOD in this animal model., Conclusions: The organoselenium compounds tested demonstrated an anti-inflammatory and antioxidant activity reducing the colon damage, being (PhSe)2 more effective than EB., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Major depression is a serious public health problem and one of the most common psychiatric disorders, and it is estimated that millions of people are affected worldwide. In addition, patients having depression present cognitive impairments, which could influence treatment adherence and long-term outcomes. Although, studies have shown that alterations in the hypothalamic-pituitary-adrenal axis, in inflammatory and antioxidant systems, and changes in intracellular pathways are involved in the cognitive impairment verified in depressive patients, it was unclear how these alterations occur. In this context, animal models of psychiatric disorders are revealed as good alternatives for the study of pathophysiology of these and associated factors. Thus, this review will highlight studies with animal models that have helped in understanding the mechanisms involved in cognitive impairment associated with depression, as well as focus on effective treatments that assist in improving both depression and cognition.

Melissa officinalis (L.) (Lamiaceae), a plant known as the lemon balm, is native to the east Mediterranean region and west Asia. Also found in tropical countries, such as Brazil, where it is popularly known as "erva-cidreira" or "melissa", it is widely used in aqueous- or alcoholic-extract form in the treatment of various disorders. The aim was to investigate in vivo its antigenotoxicity and antimutagenicity, as well as its genotoxic/mutagenic potential through comet and micronucleus assaying. CF-1 male mice were treated with ethanolic (Mo-EE) (250 or 500 mg/kg) or aqueous (Mo-AE) (100 mg/kg) solutions of an M. officinalis extract for 2 weeks, prior to treatment with saline or Methyl methanesulfonate (MMS) doses by intraperitoneal injection. Irrespective of the doses, no genotoxic or mutagenic effects were observed in blood and bone-marrow samples. Although Mo-EE exerted an antigenotoxic effect on the blood cells of mice treated with the alkylating agent (MMS) in all the doses, this was not so with Mo-AE. Micronucleus testing revealed the protector effect of Mo-EE, but only when administered at the highest dose. The implication that an ethanolic extract of M. officinalis has antigenotoxic/antimutagenic properties is an indication of its medicinal relevance.