Modulating oxidative stress counteracts specific antigen-induced regulatory T-cell apoptosis in mice.

Treg are known to have a central role in orchestrating immune responses, but less is known about the destiny of Treg after being activated by specific Ags. This study aimed to investigate the role of superoxide dismutase, an active molecule in the regulation of oxidative stress in the body, in the prevention of Treg apoptosis induced by specific Ags. Ag-specific Tregs were isolated from the DO11.10 mouse intestine. A food allergy mouse model was developed with ovalbumin as the specific Ag and here, we observed that exposure to specific Ag induced Treg apoptosis through converting the precursor of TGF-ß to its mature form inside the Tregs. Oxidative stress was induced in Tregs upon exposure to specific Ags, in which Smad3 bound the latency-associated peptide to induce its degradation, converting the TGF-ß precursor to its mature form, TGF-ß. Suppressing oxidative stress in Tregs alleviated the specific Ag-induced Treg apoptosis in in vitro experiments and suppressed experimental food allergy by preventing the specific Ag-induced Treg apoptosis in the intestine. In conclusion, exposure to specific Ags induces Treg apoptosis and it can be prevented by upregulating superoxide dismutase or suppressing reactive oxidative species in Tregs.

Caffeic acid prevents hydrogen peroxide-induced oxidative damage in SH-SY5Y cell line through mitigation of oxidative stress and apoptosis.

AIM: The aim of this study was to examine the potential ameliorative effects of caffeic acid (CA) on hydrogen peroxide (H2O2)-induced neurodegeneration in a human SH-SY5Y cell line, as well as possible mechanisms involved. METHOD: Cell proliferation was evaluated by WST-1 assay. The apoptotic index was calculated by TUNEL Assay. Antioxidant parameters were studied by measuring reactive oxygen species (ROS), lipid peroxidation (LPO) levels, and catalase (CAT) activity. The mRNA expression levels of apoptotic and anti-apoptotic genes were studied by qRT-PCRRESULTS: In this study, the pre-treatment with CA significantly suppressed H2O2-stimulated cell death and apoptosis in SH-SY5Y cell line. The mechanism by which CA pretreatment protected the cells from oxidative injury includes the decrease in ROS and LPO levels, increase in CAT activity, down-regulation of mRNA levels of Bax, cytochrome c, cas-3, cas-8, and p53, and up-regulation of anti-apoptotic Bcl-2 gene. CONCLUSION: These results reveal that CA plays a role in the protection from oxidative injury-triggered apoptosis, which makes CA a likely therapeutic compound for treatment or prevention of neurodegenerative disorders associated with oxidative injury (Fig. 5, Ref. 35).

Lipids Nutrients in Parkinson and Alzheimer's Diseases: Cell Death and Cytoprotection.

Neurodegenerative diseases, particularly Parkinson's and Alzheimer's, have common features: protein accumulation, cell death with mitochondrial involvement and oxidative stress. Patients are treated to cure the symptoms, but the treatments do not target the causes; so, the disease is not stopped. It is interesting to look at the side of nutrition which could help prevent the first signs of the disease or slow its progression in addition to existing therapeutic strategies. Lipids, whether in the form of vegetable or animal oils or in the form of fatty acids, could be incorporated into diets with the aim of preventing neurodegenerative diseases. These different lipids can inhibit the cytotoxicity induced during the pathology, whether at the level of mitochondria, oxidative stress or apoptosis and inflammation. The conclusions of the various studies cited are oriented towards the preventive use of oils or fatty acids. The future of these lipids that can be used in therapy/prevention will undoubtedly involve a better delivery to the body and to the brain by utilizing lipid encapsulation.

Apilarnil: A Novel Neuroprotective Candidate.

PURPOSE: This study was designed to investigate the effect of apilarnil on neuronal damage and related mechanisms in a sepsis model in order to demonstrate whether or not apilarnil has neuroprotective effect. METHODS: In this study, 64 adult male Sprague-Dawley species rats were randomly divided into eight groups. The rats were administered apilarnil and/or lipopolysaccharide (LPS). Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), xanthine oxidase (XOD) and testican-1 levels were measured in the brain tissue. Proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1ß], interleukin 6 [IL-6]) were measured in brain tissue. Histological examinations were performed on hippocampus and cortex tissues in all groups. Apoptotic cell count was estimated using the Tunel method to observe the apilarnil's effect on apoptosis. Purkinje cells were counted in the hippocampus to measure the protective effect of apilarnil on the hippocampus. RESULTS: Apilarnil reduced the decrease in SOD and CAT levels in the brain developing sepsis. Apilarnil reduced the increase in MDA, XOD, and testican-1 levels in the septic brain. It was observed that the number of degenerated neurons due to sepsis decreased as apilarnil dose increased. Apilarnil reduced the elevated levels of proinflammatory cytokines (IL-6, TNF-α, IL-1ß) induced by sepsis. Apilarnil prevented sepsis-related apoptosis in the brain. CONCLUSION: The neuroprotective potential of apilarnil against brain damage in the sepsis model was demonstrated and suggested that it has the potential to contribute to new therapeutic targets against various neurological disorders.

Protective effects of Urtica dioica L. on experimental testicular ischaemia reperfusion injury in rats.

In this study, it was aimed to examine the effects of Urtica dioica L. (UD) that has antioxidant feature in the experimental testicular I/R model in rats in terms of anti-apoptotic and antioxidative effects. In our study, 24 male rats were divided into three groups: control group, I/R group and I/R + UD (2 mg kg-1 ) group. Seminiferous tubule calibre measurement, Johnson score, haematoxylin-eosin staining, proliferative cell nucleus antigen (PCNA) immunohistochemical staining and TUNEL as histopathological have been conducted. The structural deterioration in the testicular on I/R group has reduced after the treatment of UD. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end labelling (TUNEL), and there was a rise in the expression of proliferating cell nuclear antigen (PCNA) in testis tissues of UD-treated rats in the I/R group. The I/R + UD group showed a decrease in malondialdehyde levels and an increase in the activities of superoxide dismutase, catalase and glutathione peroxidase in comparison with the I/R group. It could be concluded that protective effects of UD on the I/R testicles are via reduction of histological damage, apoptosis, oxidative stress and lipid peroxidation.

Apelin-13 protects human neuroblastoma SH-SY5Y cells against amyloid-beta induced neurotoxicity: Involvement of anti oxidant and anti apoptotic properties.

OBJECTIVES: We investigated the effect of apelin-13 on the cellular model of AD, amyloid-ß (Aß) treated SH-SY5Y cells in rats. METHODS: The SH-SY5Y cells were pretreated with different doses of apelin-13 (1, 2.5, 5, and 10 µg/mL), half an hour before adding 50% Aß treatment. After 24 h, cells were evaluated for survival, oxidative stress, mitochondrial calcium release, caspase-3, and cytochrome c levels, compared to control group (beta-actin). Statistical analysis was performed by SPSS 16. RESULTS: Apelin-13 at the dose of 2.5 µg/mL protected against IC50 Aß (p<0.001). Apelin-13 at doses of 1, 2.5, and 5 µg/mL showed protective effects against the reactive oxygen species (ROS) produced by Aß (p<0.001). Apelin-13 at doses of 2.5 and 5 µg/mL reduced calcium release, caspase-3, and cytochrome c (all p<0.001). CONCLUSIONS: Apelin-13 prevented apoptosis, oxidative stress, and mitochondrial toxicity and can be a suitable option for treatment of AD. The appropriate treatment strategy for humans has to be investigated in future studies.