Endogenous Antioxidant System Research Articles

Naringenin suppresses NLRP3 inflammasome activation via the mRNA-208a signaling pathway in isoproterenol-induced myocardial infarction

Objective: To investigate the cardioprotective effect of naringenin against isoproterenol (ISO)-induced cardiotoxicity in rats. Methods: Rats were divided into five groups: the normal group, the ISO group (85 mg/kg b.w.); the ISO+naringenin (50 mg/kg b.w.) group, the ISO+naringenin (100 mg/kg b.w.) group and the ISO+propranolol (10 mg/kg b.w.) group. Plasma creatine kinase-MB (CK-MB), cardiac troponin T, lactate dehydrogenase, brain natriuretic peptide (BNP), and IL-10, as well as cardiac transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF) and malondialdehyde (MDA) were examined. In addition, NLRP3 and mRNA-208a expressions were evaluated by RT-PCR analysis. Histopathological examination was also performed to assess cardiac damages. Results: Naringenin treatment significantly decreased plasma lactate dehydrogenase, CK-MB, cardiac troponin T, BNP, and IL-10, as well as cardiac TGF-β1, VEGF, and MDA while increasing p-Akt and superoxide dismutase in ISO-administered rats. It also reduced NLRP3 and mRNA-208a gene expression levels. Furthermore, naringenin improved ISO-induced cardiac damage. Conclusions: Naringenin attenuates myocardial dysfunction in ISO-treated rats by decreasing oxidative stress and increasing cardiac endogenous antioxidant system, which may be modulated partly by improvement of NLRP3 and mRNA-208a gene expression.

Smart antioxidant function enhancing (SAFE) nucleic acid therapy for ROS-related chronic diseases and comorbidities

Reactive oxygen species (ROS)-mediated oxidative stress exacerbates chronic diseases such as organ damage and neurodegenerative disorders. The Keap1-Nrf2-ARE pathway is a widely distributed endogenous antioxidant system. However, ROS under redox homeostasis regulates a wide range of life activities. Therefore, smart scavenging of excess ROS under pathological conditions is essential to treat chronic diseases safely. This study reports a smart antioxidant function enhancement (SAFE) strategy. On-demand release of nucleic acid drugs in a pathological ROS environment smartly activates the endogenous antioxidant system, thereby smartly alleviating oxidative stress in an exogenous antioxidant-independent manner. Through structural modulation and ligand modification, we develop SAFE nanoparticles based on nanohybrid complexes (SAFE-complex) adapted to brain delivery of nucleic acid drugs. SAFE-complex with homogeneous monodisperse structure efficiently treat ROS-related neurodegenerative diseases while protecting the major organ from oxidative stress damage. Moreover, SAFE-complex can stabilize storage in the form of freeze-dried powder. These data indicate that SAFE nanoparticles hold promise for treating ROS-related chronic diseases and comorbidities through rational transformation.

RETRACTED: Cladribine induces apoptosis, neuroinflammation, mitochondrial oxidative stress, tau phosphorylation and Aβ (1−42) pathway in the hippocampus: An in vivo approach

Cladribine is a purine nucleoside found to enhance toxic amyloid protein and cause memory impairment. Patients following chemotherapy treatment commonly suffer from cognitive deficits more prevalent in the elderly than adults. A previous research study revealed that cladribine has a high affinity to the brain, increases the level of amyloid precursor protein, and results in learning deficits. The study was designed to validate an animal model of cladribine administration to rats through mitochondrial oxidative stress, inflammation, apoptosis, tau phosphorylation, and amyloid-β (1–42) accumulation. In this study, all rats were orally given cladribine (0.5 and 1 mg/kg) for 28 days, resulting in impaired spatial memory confirmed by behavioural activity. On day 29, all rats were euthanized, and the hippocampal tissues were isolated and used for the estimation of neuroinflammatory markers, biochemicals parameters (glutathione, catalase, lipid peroxidation, and nitrite), amyloid-β (1–42) level, neurotransmitters, and nuclear factor kappa B analysis. Cladribine administration significantly elevated cytokines release, dysbalanced neurotransmitter concentration, and promoted the Aβ accumulation and hyperphosphorylation of tau protein. Our study outcome confirmed that cladribine produces cognitive impairment via activation of Nuclear factor kappa B, mitochondrial oxidative stress and dysbalanced of the endogenous antioxidant defence system.

Oxygen Exposure and Tolerance Shapes the Cell Wall-Associated Lipids of the Skin Commensal Cutibacterium acnes.

Cutibacterium acnes is one of the most abundant bacteria on the skin. Being exposed to oxygen and oxic stress, the secretion of the bacterial antioxidant protein RoxP ensures an endogenous antioxidant system for the preservation of skin health. To investigate the impact of the antioxidant RoxP on oxidation of the bacteria, wildtype and an isogenic roxp mutant were cultured in anaerobic and oxic conditions. The carbonylated status of proteins were recorded, as were the most significant modifications in a relative intensity of free fatty acids (FFA) and lipids containing fatty acids (FA), such as di- (DG) and triglycerides (TG), di- (DGDG) and sulfoquinozyldiacylglycerol (SQDG) and ceramides. Concerning the fatty acid types, it was observed that the free fatty acids contained mainly C12:0-C26:0 in hydroxy and acylated forms, the DG contained mainly C29:0-C37:0, the TG contained mainly C19:0-C33:0, and the DGDG/SQDGs contained very long fatty acids (C29:0-C37:0) demonstrating the interdependence of de novo synthesis of lipids and RoxP. The area of DGDG peaks (924.52, 929.56 and 930.58) were affected by bacterial growth conditions, with the exception of m/z 910.61. Moreover, the FFA unsaturation is wider in the SQDG species (C30:0 to C36:6) than in DG, TG or free FFA species. It could be concluded that both environmental oxidative statuses, as well as the prevalence of bacterial antioxidant systems, significantly shape the lipidome of C. acnes.

Gingerols synergize with anthocyanins to induce antioxidant activity in vitro.

Oxidative stress caused by free radicals contributes to the pathogenesis of multiple chronic health conditions. Phytochemicals protect against oxidative stress; however, low bioavailability from dietary sources limits their health benefits. This study aimed to assess the effects of anthocyanins and gingerols' combination on the cellular antioxidant response of Caco-2 cells against oxidative stress. A strong synergism was observed for anthocyanin-gingerol (Ac-G) w/w combined ratios of 8:1 and 2:1 (dosages of (1 + 0.125) and (1 + 0.5) μg/mL) in the cellular antioxidant activity (CAA) and cytoprotective effects, with synergistic effect indicator (SE) values of 1.41 and 1.61, respectively. The synergism of Ac-G combinations promoted cellular antioxidant defense systems and cytoprotective effects by reducing the induced GPx enzyme activity, protecting SOD enzyme activity, reducing cellular ROS generation, increasing glutathione content, and inhibiting lipid peroxidation. Thus, Ac-G combinations showed potential in supporting the endogenous antioxidant systems to protect cells from oxidation and restore physiological redox status. The Ac-G formulation is a promising healthy option that can be developed into functional foods or nutraceutical products. Furthermore, it could help address the low bioavailability of these phenolics, as higher effects were achieved when combining the same doses.

Hydroxytyrosol produced by engineered Escherichia coli strains activates Nrf2/HO-1 pathway: An in vitro and in vivo study.

This study explores the biological effects of hydroxytyrosol (HT), produced by the metabolic engineering of Escherichia coli, in a series of in vitro and in vivo experiments. In particular, a metabolically engineered Escherichia coli strain capable of producing HT was constructed and utilized. HEK293 and HeLa cells were exposed to purified HT to determine non-toxic doses that can offer protection against oxidative stress (activation of Nrf2/HO-1 signaling pathway). Male CD-1 mice were orally supplemented with HT to evaluate (1) renal and hepatic toxicity, (2) endogenous system antioxidant response, and (3) activation of Nrf2/HO-1 system in the liver. HT protected cells from oxidative stress through the activation of Nrf2 regulatory network. Activation of Nrf2 signaling pathway was also observed in the hepatic tissue of the mice. HT supplementation was safe and produced differential effects on mice's endogenous antioxidant defense system. HT biosynthesized from genetically modified Escherichia coli strains is an alternative method to produce high-quality HT that exerts favorable effects in the regulation of the organism's response to oxidative stress. Nonetheless, further investigation of the multifactorial action of HT on the antioxidant network regulation is needed.

CHEMICAL-PHARMACOLOGICAL STUDY OF COAL HUMIC SUBSTANCES FOR APPLICATION IN FOOD AND PHARMACEUTICAL INDUSTRIES

Physicochemical and pharmacological properties of the humic substances from coal of the Kansk-Achinsk coal basin, the Pereyaslovskoe deposit, have been studied. The presence of polycyclic aromatic structures and aliphatic fragments with various functional groups as substituents (carboxyl, carbonyl and quinoid, phenolic, alcoholic, ether and ester, amino and amide) was established by means of UV, IR, 13C NMR spectroscopy, fluorimetry, and elemental analysis. It has been determined by HPLC that coal humic substances are highly hydrophilic polydisperse biopolymers with medium molecular weights. According to the indicator of microbiological purity (category 3B), the content of microorganisms does not exceed the indicators required by the State Pharmacopeia of the Russian Federation (SPh XIV edition). The content of radionuclides, toxic metals (lead, cadmium, mercury, arsenic) corresponds to the norms (according to SPh XIV edition). The presence of 11 essential elements has been established. The studied humic substances belong to the V class of hazard (low-hazard substances, according to GOST 32644-2014), do not have allergising properties and cytotoxic effect within a broad concentration range. Antioxidant, immunotropic, cytoprotective properties were established in the studies of specific pharmacological activity with various experimental models. The ability to inhibit free radicals such as hydroxyl radicals (HO•) and superoxide-anion radical (O2-• should be stressed, as these radicals are able to bypass the endogenous antioxidant defense systems of the body. It is concluded that the studied humic substances of the Kansk-Achinsk coal basin, the Pereyaslovskoe deposit, are safe and effective biologically active substances of natural origin for use as a promising biologically active substance in the food and pharmaceutical industries.

Variations of Redox Balance in Different Stages of Childhood Immune Thrombocytopenic Purpura.

Few previous studies indicated the role of oxidative stress in the pathogenesis of childhood idiopathic thrombocytopenic purpura (ITP), but there are little data regarding changes in redox balance in different forms of the disease, and changes after therapeutic procedures. We aimed to investigate the values of pro-oxidants and antioxidative capacity in various forms of ITP before and after the applying therapy. The research included 102 children, classified into the following groups: (1) newly diagnosed ITP (ndITP), (2) persistent ITP, (3) chronic ITP (chITP), and (4) control groups: (A) healthy control and (B) previously experienced ITP-healthy children who had been suffering from ITP earlier. During the clinical assessment, a blood sample was taken from the patients, from which the value of pro-oxidants (index of lipid peroxidation measured as TBARS, nitrites [NO2 -], as measurement of nitric oxide [NO] production, superoxide anion radical [O2 -], and hydrogen peroxide [H2O2]) and the capacity of antioxidant protection (activity of superoxide dismutase and catalase, and quantity of reduced glutathione) were determined spectrophotometrically. Our results demonstrated that values of pro-oxidants, especially reflected through the TBARS and O2 -, were the highest in the ndITP and exacerbated chITP groups. Also, the activity of the endogenous antioxidative defense system was the lowest in these groups. Intravenous immunoglobulin therapy in the ndITP group exerted the most prominent effect on the redox balance. It can be concluded that severity and exacerbation of the ITP are closely related to the redox status.

Liver protective effect of chloroform extract of Bauhinia purpurea leaves is attributed partly to its antioxidant action and the presence of flavonoids

Context Bauhinia purpurea L. (Fabaceae) is used in the Ayurvedic system to treat various oxidative-related ailments (e.g., wounds, ulcers etc.). Therefore, it is believed that the plant also has the potential to alleviate oxidative-related liver damage. Objective This study elucidates the hepatoprotective activity of chloroform extract of B. purpurea leaves (CEBP) in paracetamol (PCM)-induced liver injury (PILI) rats. Materials and methods Male Sprague-Dawley rats (n = 6) were pre-treated once daily (p.o.) with CEBP (50–500 mg/kg) for seven consecutive days before being administered (p.o.) a hepatotoxic agent, 3 g/kg PCM. Liver enzyme levels were determined from the collected blood, while the collected liver was used to determine the activity of endogenous antioxidant enzymes and for histopathological examination. CEBP was also subjected to radical scavenging assays and phytochemical analysis. Results CEBP significantly (p < 0.05) reversed the toxic effect of PCM by increasing the serum levels of AST and ALT, and the activity of endogenous catalase (CAT) and superoxide dismutase (SOD) while reducing the liver weight/body weight (LW/BW) ratio. Other than low TPC value and radical scavenging activity, CEBP had a high antioxidant capacity when evaluated using the oxygen radical absorbance capacity (ORAC) assay. UHPLC-ESI-MS analysis of CEBP showed the presence of flavonoids. Discussion and conclusions CEBP exerts its hepatoprotective activity through a non-free radical scavenging pathway that involves activation of the endogenous enzymatic antioxidant defense system. Further study is needed to identify the responsible bioactive compounds before the plant can be developed as a future alternative hepatoprotective medicament for clinical use.

Irisin protects against doxorubicin-induced cardiotoxicity by improving AMPK-Nrf2 dependent mitochondrial fusion and strengthening endogenous anti-oxidant defense mechanisms

Irisin, a new exercise-mediated myokine, plays an important role in cardiovascular diseases by regulating cell energy metabolism. The induction of mitochondrial dysfunction and oxidative stress are the crucial mechanisms involved in doxorubicin-induced cardiomyocyte damage and cardiac dysfunction, but the mitochondria-dependent protective mechanisms of irisin in DOX-impaired cardiomyocytes are poorly understood. In this study, we exposed mouse-FNDC5 (irisin-precursor)-knockout, FNDC5 transgenic mice and their WT littermates, as well as cultured neonatal rat cardiomyocytes to DOX at a dosage of 4 mg/kg (once a week for 4 weeks) in vivo and 2 μM in vitro, respectively, then investigated how irisin alleviated DOX-induced oxidative stress and myocardial injury. Irisin knockout worsened, while irisin overexpression attenuated DOX-induced mortality, body weight loss, myocardial atrophy, damage and oxidative stress, cardiac remodeling and dysfunction in mice. Exogenous irisin supplementation (20 nM) also relieved these DOX-induced damage in cardiomyocytes. Intriguingly, irisin activated AMPK-Nrf2 signaling axis, and then up-regulated the transcription and protein expression of the downstream target genes of Nrf2, including mitochondrial fusion-related genes (mitofusin 1/2 and Optic Atrophy Type 1) and endogenous anti-oxidant genes, to promote mitochondrial fusion, improve mitochondrial dynamics and mitochondrial function, and reduced oxidative stress damage in DOX-induced cardiomyocytes. These results suggest that irisin protects the hearts from DOX-induced cardiotoxicity by improving mitochondrial dynamics and strengthening the endogenous anti-oxidant system through an AMPK-Nrf2 axis dependent manner, thus reducing DOX–induced oxidative stress injury in cardiomyocytes.

Synthesis and neuroprotective effects of new genipin derivatives against glutamate-induced oxidative damage

Glutamate-induced oxidative stress is well-known to play a crucial role in the development of neurodegenerative diseases, such as stroke. Genipin, a natural iridoid compound, has demonstrated potential neuroprotective properties but is unstable in physiological conditions. The present study aimed to develop new derivatives of genipin that exhibit improved stability and activity for the treatment of stroke. Nineteen new derivatives were thus designed and synthesized. Their neuroprotective effect against glutamate-induced injury was evaluated in HT22 cells. Among the newly synthesized derivatives, 3e demonstrated significantly greater neuroprotection and improved stability compared to genipin. Specifically, 0.01 μM of 3e was found to effectively attenuate glutamate-induced oxidative damage by inhibiting ROS over-accumulation, reducing MDA content, and restoring the endogenous antioxidative system. Further investigation revealed that 3e inhibited oxidative stress by downregulating the phosphorylation levels of p38 MAPK and activating Nrf2 and HO-1 proteins. These results suggested that 3e has the potential to serve as a promising candidate for the treatment of stroke by protecting against glutamate-induced oxidative stress.

YK11 induces oxidative stress and mitochondrial dysfunction in hippocampus: The interplay between a selective androgen receptor modulator (SARM) and exercise

Our study investigates potential neurochemical effects of (17α,20E)− 17,20-[(1-methoxyethylidene)bis(oxy)]− 3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester (YK11), a selective androgen receptor modulator (SARM), in the rat hippocampus, with a particular focus on oxidative stress and mitochondrial function, as well as its potential effect when combined with exercise (EXE). To validate YK11's anabolic potential, we performed a molecular docking analysis with the androgen receptor (AR), which showed high affinity with YK11, highlighting hydrogen interactions in Arg752. During the five-week protocol, we divided male Wistar rats into the following groups: Control, YK11 (0.35 g/kg), EXE (swimming protocol), and EXE+YK11. The administration of YK11 resulted in alterations in the endogenous antioxidant system, promoting increased oxidative stress and proteotoxic effects, impairing all mitochondrial function markers in the hippocampus. In contrast, EXE alone had a neuroprotective effect, increasing antioxidant defenses and improving mitochondrial metabolism. When combined, EXE+YK11 prevented alterations in some mitochondrial toxicity markers, including MnSOD/SOD2 and MTT reduction capacity, but did not reverse YK11's neurochemical impairments regarding increased oxidative stress and dysfunction of the mitochondrial respiratory chain and mitochondrial dynamics regulatory proteins in the hippocampus. In summary, our study identifies important pathways of YK11's hippocampal effects, revealing its potential to promote oxidative stress and mitochondrial dysfunction, suggesting that the administration of YK11 may pose potential neurological risks for athletes and bodybuilders seeking to enhance performance. These findings highlight the need for further research to assess the safety and efficacy of YK11 and SARM use in humans.

Ranuncoside’s attenuation of scopolamine-induced memory impairment in mice via Nrf2 and NF-ĸB signaling

Scopolamine is a well-known pharmacological agent responsible for causingmemory impairmentin animals, as well as oxidative stress and neuroinflammation inducer which lead to the development of Alzheimer disease. Although a cure for Alzheimer’s disease is unavailable. Ranuncoside, a metabolite obtained from a medicinal plant has demonstrated antioxidant and anti-inflammatory properties in vitro, making it a promising treatment with potential anti-Alzheimer disease properties. However, as ranuncoside has not been evaluated for its antioxidant and anti-neuroinflammatory properties in any in vivo model, our study aimed to evaluate its neurotherapeutic efficacy against scopolamine-induced memory impairment in adult male albino mice.Mice were randomly divided into four experimental groups. Mice of group I was injected with saline, group II was injected with scopolamine (1 mg/kg/day) for 3 weeks. After receiving a daily injection of scopolamine for 1 week, the mice of group III were injected with ranuncoside (10 mg/kg) every other day for 2 weeks along with scopolamine daily and group IV were injected with ranuncoside on 5th alternate days. Behavioral tests (i.e., Morris water maze and Y-maze) were performed to determine the memory-enhancing effect of ranuncoside against scopolamine's memory deleterious effect. Western blot analysis was also performed to further elucidate the anti-neuroinflammatory and antioxidant effects of ranuncoside against scopolamine-induced neuroinflammation and oxidative stress.Our results showed memory-enhancing, anti-neuroinflammatory effect, and antioxidant effects of ranuncoside against scopolamine by increasing the expression of the endogenous antioxidant system (i.e., Nrf2 and HO-1), followed by blocking neuroinflammatory markers such as NF-κB, COX-2, and TNF-α. The results also revealed that ranuncoside possesses hypoglycemic and hypolipidemic effects against scopolamine-induced hyperglycemia and hyperlipidemia in mice as well as scopolamine’s hyperglycemic effect. In conclusion, our findings suggest that ranuncoside could be a potential agent for the management of Alzheimer’s disease, hyperglycemia, and hyperlipidemia.

Mechanisms underlying the anti-aging activity of bergamot (Citrus bergamia) extract in human red blood cells.

Introduction: Aging is a process characterised by a decline in physiological functions. Reactive species play a crucial role in the aging rate. Due to the close relationship between aging and oxidative stress, functional foods rich in phytochemicals are excellent candidates to neutralise age-related changes. Aim: This investigation aims to verify the potential protective role of bergamot (Citrus bergamia, Femminello cultivar) peel and juice extract in a model of aging represented by human red blood cells (RBCs) exposed to D-Galactose (DGal). Methods: Bergamot peel and juice extracts were subjected to RP-HPLC/PDA/MS for determination of their composition in bioactive compounds. Markers of oxidative stress, including ROS production, thiobarbituric acid reactive substances (TBARS) levels -a marker of lipid peroxidation, oxidation of total protein sulfhydryl groups, as well as the expression and anion exchange capability of band 3 and glycated haemoglobin (A1c) production have been investigated in RBCs treated with D-Gal for 24 h, with or without pre-incubation for 15 min with 5 μg/mL peel or juice extract. In addition, the activity of the endogenous antioxidant system, including catalase (CAT) and superoxide dismutase (SOD), as well as the diversion of the RBC metabolism from glycolysis towards the pentose phosphate pathway shunt, as denoted by activation of glucose-6-phosphate dehydrogenase (G6PDH), have been explored. Results: Data shown here suggest that bergamot peel and juice extract i) prevented the D-Gal-induced ROS production, and consequently, oxidative stress injury to biological macromolecules including membrane lipids and proteins; ii) significantly restored D-Gal-induced alterations in the distribution and ion transport kinetics of band 3; iii) blunted A1c production; iv) effectively impeded the over-activation of the endogenous antioxidant enzymes CAT and SOD; and v) significantly prevented the activation of G6PDH. Discussion: These results further contribute to shed light on aging mechanisms in human RBCs and identify bergamot as a functional food rich in natural antioxidants useful for prevention and treatment of oxidative stress-related changes, which may lead to pathological states during aging.

Folicitin abrogates scopolamine induced hyperlipidemia and oxidative stress mediated neuronal synapse and memory dysfunction in mice

No effective drug treatment is available for Alzheimer disease, thus the need arise to develop efficient drugs for its treatment. Natural products have pronounced capability in treating Alzheimer disease therefore current study aimed to evaluate the neuro-protective capability of folicitin against scopolamine-induced Alzheimer disease neuropathology in mice. Experimental mice were divided into four groups i.e. control (single dose of 250 μL saline), scopolamine-administered group (1 mg/kg administered for three weeks), scopolamine plus folicitin-administered group (scopolamine 1 mg/kg administration for three weeks followed by folicitin administration for last two weeks) and folicitin-administered group (20 mg/kg administered for 5 alternate days). Results of behavioral tests and Western blot indicated that folicitin has the capability of recovering the memory against scopolamine-induced memory impairment by reducing the oxidative stress through up-regulating the endogenous antioxidant system like nuclear factor erythroid 2-related factor and Heme oxygenase-1 while prohibiting phosphorylated c-Jun N-terminal kinase. Similarly, folicitin also improved the synaptic dysfunction by up-regulating SYP and PSD95. Scopolamine-induced hyperglycemia and hyperlipidemia were abolished by folicitin as evidenced through random blood glucose test, glucose tolerance test and lipid profile test. All these results revealed that folicitin being a potent anti-oxidant is capable of improving synaptic dysfunction and reducing oxidative stress through Nrf-2/HO-1 pathway, thus plays a key role in treating Alzheimer disease as well as possess hyperglycemic and hyperlipidemic effect. Furthermore, a detailed study is suggested.

The Role of Oxidative Stress and Inflammation in Obesity and Its Impact on Cognitive Impairments-A Narrative Review.

Obesity is a chronic low-grade inflammatory condition that induces the generation of oxidative stress and inflammation. This oxidative stress and inflammation stimulate brain atrophy and some morphological changes in the brain that eventually result in cognitive impairments. However, there is no exact study that has summarized the role of oxidative stress and inflammation in obesity and its impact on cognitive impairments. Thus, the objective of this review is to recapitulate the current role of oxidative stress and inflammation in cognitive decline based on in vivo evidence. A comprehensive search was performed in Nature, Medline and Ovid, ScienceDirect, and PubMed, and the search was limited to the past 10 years of publication. From the search, we identified 27 articles to be further reviewed. The outcome of this study indicates that a greater amount of fat stored in individual adipocytes in obesity induces the formation of reactive oxygen species and inflammation. This will lead to the generation of oxidative stress, which may cause morphological changes in the brain, suppress the endogenous antioxidant system, and promote neuroinflammation and, eventually, neuronal apoptosis. This will impair the normal function of the brain and specific regions that are involved in learning, as well as memory. This shows that obesity has a strong positive correlation with cognitive impairments. Hence, this review summarizes the mechanism of oxidative stress and inflammation that induce memory loss based on animal model evidence. In conclusion, this review may serve as an insight into therapeutic development focusing on oxidative stress and inflammatory pathways to manage an obesity-induced cognitive decline in the future.

Ferulic acid mitigates 2-methoxyethanol-induced testicular oxidative stress via combined downregulation of FoxO1, PTEN, and modulation of Nrf2-Hmox1-NQO1 signaling pathway in rats

IntroductionFerulic acid (FERA) is a natural antioxidant that is richly found in herbs, including Ligusticum chuangxiong, Cimicifuga heracleifolia, and female ginseng (Angelica sinensis), which are utilized in modern Chinese medicine, and in cereals/grains including rice, which is mostly consumed by humans. 2METE on the other hand, is a ubiquitous substance that has many industrial applications, including use in the preparation of dyes for textiles, hydraulic fluid for automobiles, paints, and liquid soaps. It is a testicular toxin, which can induce oxidative stress in the testis of rats. Therefore, this study investigated the effect of FERA, which was concomitantly administered, against 2-methoxyethanol (2METE)-induced testicular oxidative stress in rats. MethodsMale Wistar rats totaling twenty (20), separated into four (4) groups, were used for the study. Rats in group one served as the control, rats in groups two and three were administered 100 mg/kg of 2METE only for 30 consecutive days, but only rats in group three were concomitantly treated with 50 mg/kg of FERA for the same duration, while rats in group four were treated with 50 mg/kg of FERA only. ResultsFollowing analysis, 2METE administration caused a significant reduction in the relative testes weight (RTW), NAD(P)H quinone oxidoreductase 1 (NQO1), and reduced glutathione (GSH) levels, as well as superoxide dismutase (SOD) and glutathione S-transferase (GST) activities in the testis of rats compared with the control. Moreover, 2METE administration also significantly increased the testicular levels of malondialdehyde (MDA), nitric oxide (NO), and RNA gene expressions of heme oxygenase 1 (Hmox1), nuclear factor erythroid 2-related factor 2 (Nrf2), forkhead box protein O1 (FoxO1), and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) compared with the control. FERA treatment, on the other hand, significantly decreased the testicular levels of MDA, as well as Nrf2, Hmox1, PTEN, and FoxO1 gene expressions, and significantly increased the testicular GSH and NQO1 levels, activities of GST, SOD, glutathione peroxidase (GPx), and catalase (CAT) compared with 2METE only administered rats. Conclusion2METE-induced testicular oxidative stress, marked by the depletion of the endogenous antioxidant systems, was recorded, which resulted in the activation of PTEN, FoxO1, and Nrf2 genes in rats. FERA demonstrated a strong antioxidant effect by restoring the levels and activities of the endogenous antioxidants as well as downregulating the expressions of PTEN, FoxO1, and Nrf2 in the testis of rats.

Antioxidant Therapy as an Effective Strategy against Noise-Induced Hearing Loss: From Experimental Models to Clinic.

Cochlear redox unbalance is the main mechanism of damage involved in the pathogenesis of noise-induced-hearing loss. Indeed, the increased free radical production, in conjunction with a reduced efficacy of the endogenous antioxidant system, plays a key role in cochlear damage induced by noise exposure. For this reason, several studies focused on the possibility to use exogenous antioxidant to prevent or attenuate noise-induce injury. Thus, several antioxidant molecules, alone or in combination with other compounds, have been tested in both experimental and clinical settings. In our findings, we tested the protective effects of several antioxidant enzymes, spanning from organic compounds to natural compounds, such as nutraceuticals of polyphenols. In this review, we summarize and discuss the strengths and weaknesses of antioxidant supplementation focusing on polyphenols, Q-Ter, the soluble form of CoQ10, Vitamin E and N-acetil-cysteine, which showed great otoprotective effects in different animal models of noise induced hearing loss and which has been proposed in clinical trials.

Chronic intermittent oxygen deprivation alters hippocampal cholinergic and glutamatergic system via oxido-inflammatory burden and HIF-1a/Bcl-2 activity in hypothyroid mice: Ameliorative role of Ginkgo biloba supplement

BackgroundSeveral investigations in recent years have reported a relationship between hypothyroidism or ischemia and central nervous system (CNS) beginning from fetal to adult life, but the effect of ischemia and hypothyroidism comorbidity on CNS and whether phytotherapeutic approach would attenuate this pathology remains unknown. Thus, the study investigated the role of ginkgo biloba supplement (GBS), a potent anti-oxido-inflammatory and neurorestorative plant-based product on hypoxic stress-induced neurobehavioral and neurophysiological alterations in hypothyroid mice, and the underpinning molecular mechanisms MethodologyMice were orally pre-treated with Carbimazole (1.2 mg/kg) for 14 days to develop hypothyroidism. Post-hypothyroid induction, mice were treated orally with GBS (20 mg/kg) and levothyroxine (10 µg/kg) 1 hr before 20 min exposure to hypoxia (5 times daily) for 14 consecutive days. Symptoms of behavioral deficit and neuropsychiatry were evaluated in using different models. Thereafter, brain hippocampi were sectioned for biochemical assays, immunohistochemistry and histoarchitectural studies. ResultsHerein, treatment with GBS suppressed spatial memory deficit and neuropsychiatric phenotypes and attenuated hippocampal cholinergic excitotoxicity by enhancing acetylcholinesterase enzyme and glutamatergic release in the hypothyroid mice following hypoxic stress exposure. The hippocampal endogenous antioxidant system was also upregulated with concomitant downregulation of inflammatory mediators. GBS treatment consequently regulated the hypothalamic-pituitary-adrenal axis to reduce corticosterone release. Additionally, our data showed that the suppressive impact of GBS on oxido-inflammatory mainstream decreases immunoexpression of hypoxic inducible factor-1alpha (HIF-1α) and loss of hippocampal pyramidal neurons in the CA3 region with marked increase in viable neuronal cells and upregulated immunoexpression of B-cell lymphoma-2 (Bcl-2) anti-apoptotic marker. ConclusionHerein, we deduced that prolonged intermittent exposure to hypoxia in hypothyroidism may provoke further the psychological and physiological status in the hippocampal brain region. Meanwhile, reversal of these provocative effects by the GBS treatment might be playing an important effect to suppress the hypoxic/ischemic triggered neurobehavioral and neurophysiological alterations.

The Residual Effect of C60 Fullerene on Biomechanical and Biochemical Markers of the Muscle Soleus Fatigue Development in Rats

Muscle fatigue as a defense body mechanism against overload is a result of the products of incomplete oxygen oxidation such as reactive oxygen species. Hence, C60 fullerene as a powerful nanoantioxidant can be used to speed up the muscle recovery process after fatigue. Here, the residual effect of C60 fullerene on the biomechanical and biochemical markers of the development of muscle soleus fatigue in rats for 2 days after 5 days of its application was studied. The known antioxidant N-acetylcysteine (NAC) was used as a comparison drug. The atomic force microscopy to determine the size distribution of C60 fullerenes in an aqueous solution, the tensiometry of skeletal muscles, and the biochemical analysis of their tissues and rat blood were used in this study. It was found that after the cessation of NAC injections, the value of the integrated muscle power is already slightly different from the control (5%–7%) on the first day, and on the second day, it does not significantly differ from the control. At the same time, after the cessation of C60 fullerene injections, its residual effect was 45%–50% on the first day, and 17%–23% of the control on the second one. A significant difference (more than 25%) between the pro- and antioxidant balance in the studied muscles and blood of rats after the application of C60 fullerene and NAС plays a key role in the long-term residual effect of C60 fullerene. This indicates prolonged kinetics of C60 fullerenes elimination from the body, which contributes to their long-term (at least 2 days) compensatory activation of the endogenous antioxidant system in response to muscle stimulation, which should be considered when developing new therapeutic agents based on these nanoparticles.