Regular exercise prevents oxidative stress in the brain of hyperphenylalaninemic rats

Abstract

Phenylketonuria (PKU) is caused by deficiency of phenylalanine hydroxylase, leading to accumulation of phenylalanine and its metabolites. Clinical features of PKU patients include mental retardation, microcephaly, and seizures. Oxidative stress has been found in these patients, and is possibly related to neurophysiopatology of PKU. Regular exercise can leads to adaptation of antioxidant system, improving its capacity to detoxification reactive species. The aim of this study was to verify the effects of regular exercise on oxidative stress parameters in the brain of hyperphenylalaninemic rats. Animals were divided into sedentary (Sed) and exercise (Exe) groups, and subdivided into saline (SAL) and hyperphenylalaninemia (HPA). HPA groups were induced HPA through administration of alpha-methylphenylalanine and phenylalanine for 17 days, while SAL groups (n = 16-20) received saline. Exe groups conducted 2-week aerobic exercise for 20 min/day. At 18th day, animals were killed and the brain was homogenized to determine thiobarbituric acid reactives substances (TBA-RS) content, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. Soleus muscles were collected to determine glycogen content as a marker of oxidative adaptation. Exe groups showed enhanced glycogen content. HPA condition caused an increase in TBA-RS and SOD, and reduces CAT and GPx. Exercise was able to prevent all changes seen in the HPA group, reaching control values, except for SOD activity. No changes were found in the ExeSAL group compared to SedSAL. Hyperphenylalaninemic rats were more responsive to the benefits provided by regular exercise. Physical training may be an interesting strategy to restore the antioxidant system in HPA.

Gender Dimorphism in Aspartame-Induced Impairment of Spatial Cognition and Insulin Sensitivity

“…In humans, deficiency of PAH due to genetic mutations in the gene results in phenylketonuria (PKU), which is characterized by neurotoxic hyperphenylalaninemia and microcephaly, together with visuo-spatial, executive and attention deficits [57], [58]. The mechanisms responsible for the hyperphenylalaninemia-induced brain damage are still largely unknown; however hyperphenylalaninemia has recently been shown to promote oxidative stress in rodent brains, which may contribute to the neurotoxicity in phenylketonuria [59], [60]. Oxidative stress is the result of the aberrant production of reactive oxygen and / or nitrogen species, or a decrease in the capacity of antioxidant defenses for example glutathione; and has been linked to a number of neurodegenerative diseases and to the cognitive decline associated with aging [61].…”

Negative effects of ultrafine particle exposure during forced exercise on the expression of Brain-Derived Neurotrophic Factor in the hippocampus of rats

“…Upon activation of NFE2L2, the cellular protein content of NFE2L2 increases (Kwak et al, 2002;Nguyen et al, 2003Nguyen et al, , 2004. Although, single bouts of exercise do not cause oxidative damage or increased antioxidant status in the brain (Acikgoz et al, 2006;Aksu et al, 2009), exercise training induces an adaptive response that increases the brains capacity to cope with oxidative stress (Salim et al, 2010;Mazzola et al, 2011;Vollert et al, 2011). The finding that exercise increases NFE2L2 mRNA levels in the hippocampus, is in agreement with this adaptive process suggesting that exercise might improve its antioxidant defense system by stimulating the expression of the redox-sensitive transcription factor NFE2L2.…”

Prooxidant-antioxidant balance in patients with phenylketonuria and its correlation to biochemical and hematological parameters

“…Glutathione, an important component of antioxidant defense system, was also reported to be diminished in erythrocytes for PKU patients [16]. Administration of appropriate antioxidants as adjuvant agents, in addition to the usual dietary treatment and supplementation, may prevent neurological damage in PKU patients [26].…”