Acute administration of methionine and/or methionine sulfoxide impairs redox status and induces apoptosis in rat cerebral cortex

Abstract

High plasma levels of methionine (Met) and its metabolites such as methionine sulfoxide (MetO) may occur in several genetic abnormalities. Patients with hypermethioninemia can present neurological dysfunction; however, the neurotoxicity mechanisms induced by these amino acids remain unknown. The aim of the present work was to study the effects of Met and/or MetO on oxidative stress, genotoxicity, cytotoxicity and to evaluate whether the cell death mechanism is mediated by apoptosis in the cerebral cortex of young rats. Forty-eight Wistar rats were divided into groups: saline, Met 0.4 g/Kg, MetO 0.1 g/Kg and Met 0.4 g/Kg + MetO 0.1 g/Kg, and were euthanized 1 and 3 h after subcutaneous injection. Results showed that TBARS levels were enhanced by MetO and Met+MetO 1 h and 3 h after treatment. ROS was increased at 3 h by Met, MetO and Met+MetO. SOD activity was increased in the Met group, while CAT was reduced in all experimental groups 1 h and 3 h after treatment. GPx activity was enhanced 1 h after treatment by Met, MetO and Met+MetO, however it was reduced in the same experimental groups 3 h after administration of amino acids. Caspase-3, caspase-9 and DNA damage was increased and cell viability was reduced by Met, MetO and Met+MetO at 3 h. Also, Met, MetO and Met+MetO, after 3 h, enhanced early and late apoptosis cells. Mitochondrial electrochemical potential was decreased by MetO and Met+MetO 1 h and 3 h after treatment. These findings help understand the mechanisms involved in neurotoxicity induced by hypermethioninemia.

Fetal exposure to dichloroacetic acid and impaired cognitive function in the adulthood

“…Eight rats per group. Each column represents the mean ± SD; *p < .05 compared with the control irritates could induce NF-κB activation via a mechanism involving ROS (Soares et al, 2017). In this study, we observed that DCA increased the expression of pro-inflammatory cytokines NF-κB, TNF-α, IL-6, and IL-1β, which elucidated that DCA could induce inflammation responses in the hippocampus.…”

l‐Methionine activates Nrf2‐ARE pathway to induce endogenous antioxidant activity for depressing ROS‐derived oxidative stress in growing rats

“…The regulatory effect of methionine on oxidative/antioxidant status is very complex. Some previous studies showed that acute and chronic administration of methionine could induce renal and hepatic oxidative damage, increase brain oxidative stress, depress hepatic activities of CAT and SOD, reduce cell viability, and lead to cellular death, among other effects . These studies suggest that methionine supplementation induced oxidative stress in various tissues, which were, in most instances, associated with hypermethioninemia.…”

Effect of Methionine Diet on Time-Related Metabolic and Histopathological Changes of Rat Hippocampus in the Model of Global Brain Ischemia

“…An elevated level of Met in plasma, hypermethioninemia (hMet), has been linked with memory deficits and morphological changes in the hippocampus of young rats [ 6 ]. Chronic hMet and its oxidative product, Met sulfoxide, induces cellular oxidative stress [ 7 , 8 ] in various organs and also contributes to the brain pathology [ 9 , 10 , 11 ]. Moreover, Met can undergo spontaneous self-assembly to form amyloidogenic aggregates [ 12 ], and an increased Met oxidation in the apolipoprotein A-I could nucleate amyloidogenesis, which eventually leads to the aggregation into amyloid fibrils [ 13 ].…”