The Mitochondrial Antioxidant Sirtuin3 Cooperates with Lipid Metabolism to Safeguard Neurogenesis in Aging and Depression

Neural stem cells (NSCs), crucial for memory in the adult brain, are also pivotal to buffer depressive behavior. However, the mechanisms underlying the boost in NSC activity throughout life are still largely undiscovered. Here, we aimed to explore the role of deacetylase Sirtuin 3 (SIRT3), a central player in mitochondrial metabolism and oxidative protection, in the fate of NSC under aging and depression-like contexts. We showed that chronic treatment with tert-butyl hydroperoxide induces NSC aging, markedly reducing SIRT3 protein. SIRT3 overexpression, in turn, restored mitochondrial oxidative stress and the differentiation potential of aged NSCs. Notably, SIRT3 was also shown to physically interact with the long chain acyl-CoA dehydrogenase (LCAD) in NSCs and to require its activation to prevent age-impaired neurogenesis. Finally, the SIRT3 regulatory network was investigated in vivo using the unpredictable chronic mild stress (uCMS) paradigm to mimic depressive-like behavior in mice. Interestingly, uCMS mice presented lower levels of neurogenesis and LCAD expression in the same neurogenic niches, being significantly rescued by physical exercise, a well-known upregulator of SIRT3 and lipid metabolism. Our results suggest that targeting NSC metabolism, namely through SIRT3, might be a suitable promising strategy to delay NSC aging and confer stress resilience.

Microfluidic Characterization of Red Blood Cells Microcirculation under Oxidative Stress

Microcirculation is one of the basic functional processes where the main gas exchange between red blood cells (RBCs) and surrounding tissues occurs. It is greatly influenced by the shape and deformability of RBCs, which can be affected by oxidative stress induced by different drugs and diseases leading to anemia. Here we investigated how in vitro microfluidic characterization of RBCs transit velocity in microcapillaries can indicate cells damage and its correlation with clinical hematological analysis. For this purpose, we compared an SU-8 mold with an Si-etched mold for fabrication of PDMS microfluidic devices and quantitatively figured out that oxidative stress induced by tert-Butyl hydroperoxide splits all RBCs into two subpopulations of normal and slow cells according to their transit velocity. Obtained results agree with the hematological analysis showing that such changes in RBCs velocities are due to violations of shape, volume, and increased heterogeneity of the cells. These data show that characterization of RBCs transport in microfluidic devices can directly reveal violations of microcirculation caused by oxidative stress. Therefore, it can be used for characterization of the ability of RBCs to move in microcapillaries, estimating possible side effects of cancer chemotherapy, and predicting the risk of anemia.

Synthesis and Cross-Linking Properties of Melamine Formaldehyde Oligomers with Peroxy Groups

Melamine formaldehyde oligomers with peroxy groups (MFOP) have been synthesized based on melamine or urea and melamine in the presence of tert-butyl peroxymethanol or tert-butyl hydroperoxide. Zinc oxide was used as a catalyst. The effect of peroxide nature, ratio of the starting components and process time on the characteristics and yield of MFOP has been studied. The structure of the synthesized MFOP was confirmed by IR- and PMR-spectroscopy. The chemistry of the cross-linked structures formation was studied. The possibility of using such oligomers as a cross-linking agent for the mixtures based on TGM-3 oligoesteracrylate is shown.

Chrysin and rutin protect against hydrogen peroxide and tert-butyl hydroperoxide induced oxidative cell damage

Objective: Chrysin and rutin are two dietary flavonoids lying in fruits or honey bee’s products. Their pharmacological properties include antioxidant, anti-inflammatory, anticancer, neuroprotection and immunomodulatory. In the current study, the potentiality of chrysin and rutin to protect human gingival fibroblasts against oxidative cell damage has been investigated in vitro. Method: Human gingival fibroblasts, passage 3, were concomitantly put in contact with the cytotoxic compounds and chrysin or rutin for 24 h at 37 °C, 5% CO2 atmosphere, and 96% humidity. The amount of viable cell after the incubated time was recorded by using the thiazolyl blue tetrazolium bromide (MTT) assay. Results: Chrysin in all tested concentration didn’t exhibit any cytoprotective effect against the tert-butyl hydroperoxide-induced oxidative cell damage. Moreover, chrysin in a low concentration (5 and 10 µg/mL) didn’t protect the fibroblasts against oxidative cell damage induced by the hydrogen peroxide. However, chrysin in a concentration of 20 µg/mL showed a significant cytoprotective activity in the hydrogen peroxide-induced cell damage (p < 0.05). Rutin in all tested concentrations protected fibroblasts against hydrogen peroxide and tert-butyl hydroperoxide-induced oxidative cell damage. The cytoprotective effect of rutin didn’t increase with the increase of the concentration when hydrogen peroxide is used to induce oxidative cell damage. However, rutin has protected cells against the tert-butyl hydroperoxide cytotoxicity in a concentration dependent manner. Conclusion: Given to the interesting cytoprotective activities exhibited by chrysin and rutin, further investigations to highlight their cytoprotective involved mechanisms are justified. Keywords: Chrysin, Cytoprotective, Fibroblasts, Rutin.

Echinacoside Upregulates Sirt1 to Suppress Endoplasmic Reticulum Stress and Inhibit Extracellular Matrix Degradation In Vitro and Ameliorates Osteoarthritis In Vivo

Background. Osteoarthritis (OA) is a progressive illness that destroys cartilage. Oxidative stress is a major contributor of OA, while endoplasmic reticulum (ER) stress is the key cellular damage under oxidative stress in chondrocytes. Echinacoside (ECH) is the main extract and active substance of Cistanche, with potent antioxidative stress (OS) properties, and currently under clinical trials in China. However, its function in OA is yet to be determined. Purpose. We aimed to explore the specific role of ECH in the occurrence and development of OA and its underlying mechanism in vivo and in vitro. Methods. After the mice were anesthetized, the bilateral medial knee joint meniscus resection was performed to establish the DMM model. TBHP was used to induce oxidative stress to establish the OA model in chondrocytes in vitro. Western blot and RT-PCR were used to evaluate the level of ER stress-related biomarkers such as p-PERK/PERK, GRP78, ATF4, p-eIF2α/eIF2α, and CHOP and apoptosis-related proteins such as BAX, Bcl-2, and cleaved caspase-3. Meanwhile, we used SO staining, immunofluorescence, and immunohistochemical staining to evaluate the pharmacological effects of ECH in mice in vivo. Results. We demonstrated the effectiveness of ECH in suppressing ER stress and restoring ECM metabolism in vitro. In particular, ECH was shown to suppress tert-Butyl hydroperoxide- (TBHP-) induced OS and subsequently lower the levels of p-PERK/PERK, GRP78, ATF4, p-eIF2α/eIF2α, and CHOP in vitro. Simultaneously, ECH reduced MMP13 and ADAMTS5 levels and promoted Aggrecan and Collagen II levels, suggesting ECM degradation suppression. Moreover, we showed that ECH mediates its cellular effects via upregulation of Sirt1. Lastly, we confirmed that ECH can protect against OA in mouse OA models. Conclusion. In summary, our findings indicate that ECH can inhibit ER stress and ECM degradation by upregulating Sirt1 in mouse chondrocytes treated with TBHP. It can also prevent OA development in vivo.

Influence of tungsten compounds on reaction of 1-octene epoxidation by tert-butyl hydroperoxide and hydroperoxide decomposition

Catalytic ability of tungsten compounds in the reaction of hydroperoxide epoxidation of 1- octene and tert-butyl hydroperoxide decomposition was investigated. It is shown that the nature of ligand has significant effect on the catalytic activity of tungsten compounds in these reactions. It is established that boride and silicide of tungsten are the best choice for epoxidation reaction, whereas tungsten carbide exhibits poor activity. Tungsten boride is also the most active in the hydroxide decomposition reaction.

The Zebrafish Embryo as a Model to Test Protective Effects of Food Antioxidant Compounds

The antioxidant activity of food compounds is one of the properties generating the most interest, due to its health benefits and correlation with the prevention of chronic disease. This activity is usually measured using in vitro assays, which cannot predict in vivo effects or mechanisms of action. The objective of this study was to evaluate the in vivo protective effects of six phenolic compounds (naringenin, apigenin, rutin, oleuropein, chlorogenic acid, and curcumin) and three carotenoids (lycopene B, β-carotene, and astaxanthin) naturally present in foods using a zebrafish embryo model. The zebrafish embryo was pretreated with each of the nine antioxidant compounds and then exposed to tert-butyl hydroperoxide (tBOOH), a known inducer of oxidative stress in zebrafish. Significant differences were determined by comparing the concentration-response of the tBOOH induced lethality and dysmorphogenesis against the pretreated embryos with the antioxidant compounds. A protective effect of each compound, except β-carotene, against oxidative-stress-induced lethality was found. Furthermore, apigenin, rutin, and curcumin also showed protective effects against dysmorphogenesis. On the other hand, β-carotene exhibited increased lethality and dysmorphogenesis compared to the tBOOH treatment alone.

Alkyl Hydroperoxide Reductase as a Determinant of Parasite Antiperoxide Response in Toxoplasma gondii

Toxoplasma gondii is a protozoan parasite that is widely parasitic in the nucleated cells of warm-blooded animals. Bioinformatic analysis of alkyl hydroperoxide reductase 1 (AHP1) of T. gondii is a member of the Prxs family and exhibits peroxidase activity. Cys166 was certified to be a key enzyme active site of TgAHP1, indicating that the enzyme follows a cysteine-dependent redox process. TgAHP1 was present in a punctate staining pattern anterior to the T. gondii nucleus. Oxidative stress experiments showed that the ∆Ahp1 strain was more sensitive to tert-butyl hydroperoxide (tBOOH) than hydrogen peroxide (H2O2), indicating that tBOOH may be a sensitive substrate for TgAHP1. Under tBOOH culture conditions, the ∆Ahp1 strain was significantly less invasive, proliferative, and pathogenic in mice. This was mainly due to the induction of tBOOH, which increased the level of reactive oxygen species in the parasites and eventually led to apoptosis. This study shows that TgAHP1 is a peroxisomes protein with cysteine-dependent peroxidase activity and sensitive to tBOOH.