Antioxidant Defense Research Articles

MsDUF3700 overexpression enhances aluminum tolerance in alfalfa shoots.

This study identified a gene associated with aluminum stress through GWAS, which regulates aluminum tolerance in alfalfa by contributing to the antioxidant system. Aluminum (Al) ions precipitate in acidic soils with a pH < 5.5, where they are absorbed alongside other nutrients by plants, negatively impacting plant growth. Alfalfa, the most widely grown perennial legume forage in the world, is especially vulnerable to acidic soil conditions. Our research pinpointed MsDUF3700 as a potential gene linked to Al-response traits via genome-wide association analysis in Medicago sativa. MsDUF3700 encodes the domain of unknown function (DUF). We observed higher expression of MsDUF3700 in Al-tolerant alfalfa compared to Al-sensitive ecotypes. MsDUF3700-overexpressing transgenic alfalfa (MsDUF3700-OE) showed shorter root elongation and higher Al accumulation in roots than wild type (WT) under Al conditions. However, the shoots of MsDUF3700-OE lines showed enhanced growth rates under both normal and Al stress conditions. Under Al stress, MsDUF3700-OE lines showed increased H2O2 and malondialdehyde (MDA) levels in the roots, alongside reduced catalase activity, In contrast, the shoots showed an inverse trend. In addition, we found that MsDUF3700-OE alfalfa plants had high Al accumulation in the roots and low Al accumulation in the shoots. Transcripts of MsALS3 and MsPALT1, homologs of Al translocation in alfalfa, were downregulated, while MsNrat1, a homolog of transporters absorb Al, was upregulated in the roots of MsDUF3700-OE in alfalfa. Our research indicates that MsDUF3700 plays a role in aluminum stress by participating in antioxidative defense and facilitating aluminum transport from roots to shoots.

Macromolecular crowding and bicarbonate enhance the hydrogen peroxide-induced inactivation of glyceraldehyde-3-phosphate dehydrogenase.

The active site Cys residue in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is sensitive to oxidation by hydrogen peroxide (H2O2), with this resulting in enzyme inactivation. This re-routes the carbon flux from glycolysis to the pentose phosphate pathway favoring the formation of NADPH and synthetic intermediates required for antioxidant defense and repair systems. Consequently, GAPDH inactivation serves as a redox switch for metabolic adaptation under conditions of oxidative stress. However, there is a major knowledge gap as to how GAPDH is efficiently oxidized and inactivated, when the increase in intracellular H2O2 is modest, and there is a high concentration of alternative (non-signaling) thiols and efficient peroxide removing systems. We have therefore explored whether GAPDH inactivation is enhanced by two factors of in vivo relevance: macromolecular crowding, an inherent property of biological environments, and the presence of bicarbonate, an abundant biological buffer. Bicarbonate is already known to modulate H2O2 metabolism via formation of peroxymonocarbonate. GAPDH activity was assessed in experiments with low doses of H2O2 under both dilute and crowded conditions (induced by inert high molecular mass polymers and small molecules), in both the absence and presence of 25 mM sodium bicarbonate. H2O2-induced inactivation of GAPDH was observed to be significantly enhanced under macromolecular crowding conditions, with bicarbonate having an additional effect. These data strongly suggest that these two factors are of major importance in redox switch mechanisms involving GAPDH (and possibly other thiol-dependent systems) within the cellular environment.

Global Insights into the Lysine Acetylome Reveal the Role of Lysine Acetylation in the Adaptation of Bacillus altitudinis to Salt Stress.

Bacillus altitudinis is a well-known beneficial microorganism in plant rhizosphere, capable of enhancing plant growth and salt tolerance in saline soils. However, the mechanistic changes underlying salt tolerance in B. altitudinis at the level of post-translational modifications remain unclear. Here, diverse lysine modifications including acetylation, succinylation, crotonylation, and malonylation were determined in the B. altitudinis response to salt stress by immunodetection, and the acetylation level greatly increased under salt stress. The in-depth acetylome landscape showed that 1032 proteins in B. altitudinis were differentially acetylated under salt stress. These proteins were involved in many physiological aspects closely related to salt tolerance like energy generation and conversion, amino acid synthesis and transport, cell motility, signal transduction, secretion system, and repair system. Moreover, we also identified the differential acetylation of key enzymes involved in the major osmolyte biosynthesis and conversion and antioxidant defenses. Thiol peroxidase (TPX), a key protective antioxidant enzyme, had 3 upregulated acetylation sites (K7/139/157) under salt stress. Site-specific mutations demonstrated that K7/139/157 acetylation strongly regulated TPX function in scavenging intracellular ROS, thereby impacting bacterial growth under salt stress. To our knowledge, this is the first study showing that bacteria adaptation to salt stress occurs at the level of PTMs.

Pentoxifylline ameliorates carbamazepine-induced hepatotoxicity via down expression of CYP3A4 and NF-kB gene expression in the rat: in vivo study

Drug-induced liver injury (DILI) is a serious complication of many drugs, including carbamazepine; this study investigates the protective effect of pentoxifylline (PTX) against DILI induced by carbamazepine in rat models by attenuating CYP3A4 and NF-κB gene expression. Forty rats were divided into five groups: the control group received no treatment, the induction group received 50 mg/kg carbamazepine orally for 28 days, and three groups received PTX (100, 200, and 300 mg/kg) once daily for one hour before carbamazepine induction for 28 days. Then, the rats were euthanized, and blood and liver tissue were collected for biochemical, gene expression, and histopathology. PTX attenuates the carbamazepine-induced increased CYP3A4 and NF-κB gene expression, with the highest dose showing the best result. PTX also reduced aspartate aminotransferase, alanine aminotransferase, and malondialdehyde, while glutathione levels increased. In conclusion, PTX is highly efficacious in preventing and restoring the liver cells’ normal morphology and cellular function caused by carbamazepine hepatotoxicity. A possible mechanism of the PTC effect is hindering oxidative stress by scavenging free radicals and enhancing the body’s natural defense antioxidant system. Additionally, it exerts an anti-inflammatory impact by modulating NF-κB gene expression.

The Transcription Factor StuA Regulates Oxidative Stress-Responsive Genes in Trichophyton rubrum

Fungi can remarkably sense and adapt to various extracellular stimuli and stress conditions. Oxidative stress, which results from an imbalance between reactive oxygen species production and antioxidant defenses, leads to cellular damage and death. In Trichophyton rubrum, oxidative stress is managed by a complex antioxidant system, including thioredoxins, glutathione, catalases, peroxidases, and superoxide dismutase, with glutathione playing a crucial role. The fungus also responds to oxidative stress through critical pathways such as the glycerol high-osmolarity pathway, activator protein 1 transcription factor, and responsive regulator SKN7. To better understand the role of the transcription factor StuA in regulating oxidative stress-related genes within these pathways, we conducted gene expression studies in ΔstuA mutant and wild-type strains of T. rubrum cultivated in keratin and under oxidative stress induced by hydrogen peroxide. Our results revealed significant downregulation of essential antioxidant genes, including glutathione transferases and catalases, in the ΔstuA mutant. Moreover, catalase and glutathione S-transferase activities were impaired in the mutants under stress conditions, highlighting the impact of this mutation. These findings underscore the critical role of StuA in the oxidative stress response and fungal pathogenesis and provide new insights into T. rubrum’s adaptive mechanisms.

Therapeutic potency of kaempferol against Naja haje venom induced neurotoxicity, inflammation, biological activities, and antioxidant system damage: a pre-clinical antivenom evaluation.

Naja haje envenoming manifests organ system disorders leading to severe fatalities due to the venom's toxins. The neutralizing capacity of kaempferol has been reported against some medically significant snake venoms with exception of N. haje venom (NhV). This current study assessed the neutralizing profile of kaempferol against toxicities induced by NhV using in vitro and in vivo methods. In in vitro, NhV induced wide spectrum of toxic biological activities with substantial increase in hemorrhagic, anticoagulating, and hemolytic effects. Likewise in the in vivo study, the venom caused hematological disorders by inducing acute anemia, thrombocytopenia, and leucopenia in envenomed rats. Also, the venom caused detrimental effect on the antioxidant defense system of the brain through significant (P < 0.05) elevation of malondialdehyde (MDA), nitrite (NIT), and suppression of reduce glutathione (GSH) antioxidant, superoxide dismutase (SOD), catalase (CAT), and glutathione transferase (GST) enzymes. Additionally, the levels of neurotoxicity biomarkers, monoamine oxidase (MAO) and acetylcholinesterase (AChE), and pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were significantly (P < 0.0.5) enhanced by NhV in the brain of envenomed rats. Severe pathohistological effects were observed in brain tissues of the envenomed rats. However, kaempferol substantially (P < 0.05) inhibited the NhV-induced biological activities, normalized the hematological disorders, enhanced antioxidants system functions, and significantly (P < 0.05) suppressed the levels of neurotoxicity biomarkers and pro-inflammatory cytokines. Severe structural alterations observed in the brain tissues were ameliorated after kaempferol treatment. Further exploration of kaempferol could lead to the development of an alternative therapy for treatment of N. haje envenoming.

Anti-inflammatory and antioxidant succinyl-chitosan oligosaccharide protects human epidermal cell and mouse skin against ultraviolet B-induced photodamage

Ultraviolet B (UVB) irradiation from sunlight is one of the primary environmental factors that causes photodamage to the skin. The aim of this study was to prepare succinyl-chitosan oligosaccharide (SU-COS) and evaluate its protective effects and related molecular mechanisms against UVB-induced photodamage for the first time. SU-COS (substitution degree: 69.26 %, molecular weight: 6400 Da) was shown to have excellent biocompatibility and to effectively promote the migration of human epidermal HaCaT cells. UVB irradiation was used to develop photodamage models in HaCaT cells and murine skin. In vitro, treatment with SU-COS significantly increased the cell survival ratio by >11 % while concurrently reducing reactive oxygen species formation, preserving normal cytoskeletal morphology, stabilizing the cell cycle, and decreasing the apoptosis ratio. The SU-COS intervention also demonstrated a reparative effect on UVB-damaged mouse skin by reducing skin erythema and water loss, relieving crusting, and maintaining the epidermis thickness of the skin and the stability of collagen fibers. The observed changes in both in vitro and in vivo results were accompanied by significant modulation of gene and protein expression associated with the cellular cycle, collagen synthesis, extracellular matrix degradation, antioxidant defense, and inflammation. Overall, SU-COS holds immense promise for applications in repairing photodamage.

Nanoplastics indirectly compromise lettuce growth in hydroponic systems via microbial extracellular vesicles derived from Curvibacter fontanus

Recent studies confirm that nanoplastics (NP) cause severe microbial imbalances in various ecosystems, significantly affecting microbial diversity and abundance. Hydroponic systems vital for lettuce production are increasingly threatened by NP contamination in irrigation water and this issue is gaining global attention. This study investigates microbial species in hydroponic irrigation water altered by NP exposure and their impact on lettuce growth. While NP (108-1010 particles/L) did not directly harm or accumulate in lettuce, significant changes in water parameters and microbial communities were observed, particularly an increase in Curvibacter fontanus abundance. Inoculation of sterile irrigation water with NP and C. fontanus led to lettuce mortality, suggesting C. fontanus as a critical mediator. Furthermore, extracellular vesicles (EVs) isolated from C. fontanus, treated with NP, were shown to suppress leaf development, growth, antioxidant defenses, and lettuce survival. This study concludes that NP-induced microbial shifts, particularly involving C. fontanus EVs, indirectly harm hydroponic lettuce production.

Assessing the Effects of Palm Oil Consumption on Life Expectancy, Metabolic Markers, and Oxidative Stress in Drosophila melanogaster.

Palm oil is the world's second most consumed vegetable oil, sourced from the tropical palm tree Elaeis guineensis. Its consumption has been associated with a higher incidence of cardiovascular disease, largely due to its elevated palmitic acid content, however those studies are contradictory and inconclusive. Wishing to contribute to this issue, the present study aims to investigate the molecular and toxicological effects of this oil and the involvement of oxidative stress, given its role in metabolic dysfunctions using Drosophila melanogaster. This study examines survival rates, and locomotor performance, oxidative status by analysis of lipid peroxidation, ROS formation, thiol levels and antioxidant enzyme activity, and metabolic parameters such as cholesterol and triglycerides, glucose, trehalose and glycogen levels. Exposure to palm oil concentrations of 10% and 30% resulted in a shortened lifespan, reduced locomotor performance, and increased lipid peroxidation, with lower thiol levels and antioxidant enzyme modulation. Cholesterol levels was increased whereas energetic fuels as glucose and glycogen and trehalose were decreased mainly after 10 days of exposure. These findings underscore the detrimental effects of high-fat diets containing palm oil on lifespan, antioxidant defenses, and metabolism in Drosophila melanogaster. This data highlights the potential risk associated with the habitual consumption of palm oil in the daily diet by population, particularly concerning cardiovascular health and metabolic function.

Role of NADPH Quinone Reductase 1 (NQO1) Polymorphism in Prevention, Diagnosis, and Treatment of Gastrointestinal Cancers.

Most cancer deaths are related to gastrointestinal (GI) cancers. Several environmental and genetic factors are effective in the occurrence of GI cancers, such as esophageal, stomach, colorectal, liver, and pancreatic cancers. In addition to risk factors related to lifestyle, reactive oxygen species (ROS) also play a role in GI cancers, and an increase in the amount of free radicals can lead to oxidative stress and increase the probability of malignancies. NQO1 is part of the body's antioxidant defense system that protects cells against mutagenesis and carcinogenesis. NQO1 is responsible for reducing quinones to hydroquinone and preventing the generation of ROS by catalyzing the reaction. The existence of single nucleotide polymorphisms (SNPs) of NADPH Quinone Reductase 1 (NQO1), such as 609C>T NQO1, leads to a decrease in NQO1 enzyme activity. Some NQO1 polymorphisms may increase the risk of gastrointestinal cancer. So, the C609T polymorphism in the NQO1 gene has been found to be effective in causing gastrointestinal cancers. On the other hand, it is very important to know the role of biomarkers in the prognosis and management of cancer treatment. Therefore, this study investigated the role of NQO1 as a biomarker in the management of gastrointestinal cancers (prevention, diagnosis and treatment).

Tanshinone Alleviates UVA-induced Melanogenesis in Melanocytes via the Nrf2-regulated Antioxidant Defense Signaling Pathway.

As a complex of natural plant compounds, tanshinone is renowned for its remarkable antioxidant properties. However, the potential impact of tanshinone on melanocyte pigmentation regulation has yet to be elucidated. This study aimed to explore the protective effects of tanshinone I (T-I) and dihydrotanshinone (DHT) on melanogenesis by modulating nuclear factor E2-related factor 2 (Nrf2) signaling and antioxidant defenses in human epidermal melanocyte (HEM) cells. HEM cells and Nrf2 knockdown HEM cells were subjected to ultraviolet A (UVA) and treated with T-I and/or DHT. Then, the anti-melanogenic properties of T-I and DHT were examined by assessing tyrosinase activity, melanogenesis-related proteins, and melanin content in UVA-irradiated HEM cells. Furthermore, the antioxidant activities of T-I and DHT were evaluated by assessing oxidant formation and modulation of Nrf2-related antioxidant defenses, including reactive oxygen species (ROS), glutathione (GSH) content, and the activity and expression of antioxidant enzymes, such as catalase (CAT), heme oxygenase-1 (HO-1), and superoxide dismutase (SOD). Our findings revealed that T-I and DHT diminished melanogenesis in UVAirradiated HEM cells, activated Nrf2-antioxidant response element signaling, and enhanced antioxidant defenses in the irradiated cells. Furthermore, Nrf2 knockdown by shRNA abolished the anti-melanogenesis effects of T-I and DHT on HEM cells against oxidative damage. These results suggest that T-I and DHT inhibit UVA-induced melanogenesis in HEM cells, possibly through redox mechanisms involving Nrf2 signaling activation and increased antioxidant defenses. This indicates that T-I and DHT have potential as whitening agents in cosmetics and medical treatments for hyperpigmentation disorders.

Effect of natural astaxanthin on sperm quality and mitochondrial function of breeder rooster semen cryopreservation

Cryopreservation causes higher reactive oxygen species (ROS) concentrations, leading to oxidative stress and lipid peroxidation damaging sperm, and using antioxidants can improve semen quality after freeze-thaw. Natural astaxanthin (ASTA) can be inserted into cell membranes and its antioxidant properties are stronger than other antioxidants. We aimed to investigate the effects of ASTA supplementation in the Beltsville Poultry Semen Extender (BPSE) on post-thaw rooster semen quality and to explore the potential mechanism of rooster semen quality change. The qualifying semen ejaculates collected from 30 adult male Jinghong No. 1 laying hen breeder roosters (65 wk old) were pooled, divided into four aliquots, and diluted with BPSE having different levels of ASTA (0, 0.5, 1, or 2 μg/mL). Treated semen was cryopreserved and kept in liquid nitrogen. The entire experiment was replicated three times independently. Sperm viability, motility, curvilinear velocity, amplitude of lateral head displacement, straightness, plasma membrane integrity, and acrosome integrity were observed to be highest (P < 0.05) with 1 μg/mL ASTA at freeze-thawing. Higher (P < 0.05) antioxidant enzyme (CAT-like, SOD) activities and free radical (·OH, O2.-) scavenging ability, less ROS and malondialdehyde (MDA) concentrations were recorded with the addition of appropriate concentrations of ASTA compared to control. In addition, the levels of mitochondrial membrane potential (MMP), adenosine triphosphate (ATP), and lactate dehydrogenase (LDH) in the 1 μg/mL ASTA group improved compared to the control group, and decreased the amount of AIF protein level but increased the Bcl-2 protein level (P < 0:05). Collectively, these results demonstrate that adding ASTA in the BPSE promoted rooster freeze-thaw sperm quality, which may be related to reducing ROS levels, protecting the antioxidant defense system, preventing lipid peroxidation, improving mitochondrial structural and functional integrity, and inhibiting sperm apoptosis.

Glutathione S-Transferase Contributes to the Resistance of Megalurothrips usitatus Against Lambda-Cyhalothrin by Strengthening Its Antioxidant Defense Mechanisms.

The damage caused by Megalurothrips usitatus, a common pest, has significantly affected the Chinese vegetable industry. The inappropriate application of chemical pesticides has caused M. usitatus to become highly resistant to conventional insecticides. Glutathione S-transferase (GST), known for its multifunctional properties, contributes to detoxification and antioxidation. It enhances insects' adaptability to pesticides by facilitating the elimination of lipid peroxidation products resulting from pyrethroid insecticides. This research employed RT-qPCR to identify GST genes that exhibited significant expression in response to lambda-cyhalothrin stress. It also quantified changes in antioxidant and apoptosis markers within the M. usitatus under lambda-cyhalothrin exposure. The functional significance of GST was validated by assessing alterations in the antioxidant defense system and resistance to lambda-cyhalothrin following the inhibition of GST activity. The study's outcomes indicated that MuGSTs1 was markedly upregulated in response to lambda-cyhalothrin stress (p < 0.0001). The GST activity was effectively suppressed by the specific inhibitor, diethyl maleate, achieving an inhibition rate of 64.05%. Following the inhibition of GST, the overall antioxidant capacity was reduced by 3.1-fold compared with the control, and the M. usitatus exhibited a 7.91-fold increase in sensitivity to lambda-cyhalothrin. These findings confirm the pivotal role of GST in the oxidative stress response of the M. usitatus and their contribution to the development of resistance to lambda-cyhalothrin through enhanced antioxidant defenses. This research offers valuable perspectives on the adaptive reactions of insects to chemical stressors, facilitating the management of resistance and the formulation of effective pest control strategies.

α -lipoic acid supplementation reduces oxidative stress and inflammation in red skeletal muscle of insulin-resistant rats

α -lipoic acid (ALA) is an eight-carbon saturated fatty acid with strong antioxidant activity. Despite previous reports of ALA's protective properties in treating cardiovascular and metabolic diseases (including insulin resistance and diabetes), little is known about the compound's effects on skeletal muscle metabolism. In particular, the effect of ALA on glycooxidative and nitrosative damage in red muscles during insulin resistance is unknown. This study investigated the therapeutic potential of ALA on the antioxidant barrier as well as oxidative, nitrosative and carbonyl stress in the red skeletal muscle of rats with high-fat diet-induced insulin resistance. Male Wistar cmdb/outbred rats were divided into four equal groups: control diet (CTRL), high fat diet (HFD), CTRL+ALA (30 mg/kg body weight for 4 weeks; intragastrically) and HFD+ALA. Enzymatic and nonenzymatic antioxidant systems, protein and lipid glycoxidation, nitrosative stress, and selected inflammatory/apoptosis parameters were assessed using colorimetric, fluorimetric, and immune-enzymatic methods. ALA lowered body weight and glucose metabolism parameters in insulin-resistant rats. ALA not only strengthened enzymatic antioxidant defense (by increasing superoxide dismutase, catalase and glutathione peroxidase activity) but also stimulated the synthesis of non-enzymatic GSH. ALA supplementation inhibited lipid peroxidation (decreased lipid hydroperoxides and malondialdehyde content) and prevented protein oxidation (by lowering advanced oxidation protein products concentration) in red muscle. ALA's multifactorial actions on muscle tissue also included inhibition of inflammation and apoptosis, requiring further research to elucidate its effects in metabolic diseases.

Natural Remedies and Health; A Review of Bee Pollen and Bee Bread Impact on Combating Diabetes and Obesity.

Diabetes and obesity are complicated multifactorial conditions that have been highlighted as a significant global burden for both health care and national budgets and their complications are considered a substantial public health concern. This review focuses on the potential anti-diabetic and anti-obesity properties of bee pollen (BP) and bee bread (BB), two bee products with a long history of use in traditional medicine and supplemental nutrition. Recent studies, encompassing cellular models, experimental models, and clinical trials, have shed light on the therapeutic potential of these bee products. BP and BB are rich in phytochemical constituents like flavonoids and phenolic acids, which are believed to confer their anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, and anti-obesity properties. These bee products have shown promising results in the treatment of diabetes and obesity, underscoring their potential as natural therapeutic tools. BP and BB possess properties that aid in decreasing blood glucose levels and body weight. BP and BB have been found to enhance insulin sensitivity, alleviate oxidative stress, regulate appetite, adjust levels of hormones linked to obesity, while bolstering anti-oxidant defense systems. BP and BB nutritional qualities and health benefits make them promising candidates for further research towards diabetes and obesity treatment strategies.

Efficacy of copper and silver nanoparticles on seedling growth, biochemical and antioxidant potential of Capsicum annuum L., in vitro and ex vitro

Metallic nanoparticles (MNPs) were synthesized using the chemical reduction method and evaluated in vitro and ex vitro on Capsicum annuum. The impact of MNPs, namely Ag, Cu, CuAg NPs, Silver nitrate (AgNO3), and Copper sulfate pentahydrate (CuSO4·5H2O) as bulk salts, on the physiological, biochemical, and antioxidative profiles of seedlings in C. annuum were examined in this work. Both NPs Primed (NPsP) and NPs Supplemented (NPsS) seeds showed 80–90 % and 90–100 % germination, respectively, after 15 days of inoculation on Murashige and Skoog medium (MS) medium, compared to the control (75 %) and 93–97 % in vitro. The seedling length, weight, and vigour index improved significantly in response to in vitro and ex-vitro NP administration. After 45 days of nanoparticle (NPs) treatment, the levels of chlorophyll and carotenoids in NPsP seedlings increased by 65–244 % and 41–203 % in ex vitro, respectively, compared to NPsS seedlings, which showed an increase of 4–114 % and 26–107 %, respectively. Additionally, the total phenolic content (TPC) and total flavonoid content (TFC) were significantly enhanced in NPsP seedlings, showing an increase of 79–173 % and 62–168 % in ex vitro, compared with NPsS seedlings, which showed an increase of 3–73 % and 22–98 %, respectively. MNPs increased the total protein content in NPsP seedlings by 26–106 % in ex vitro (5–113 %), compared to NPsS seedlings. In the NPsP seedlings, superoxide dismutase (SOD), peroxidase (POD), and proline content rose by 15–47 %, 38–83 %, and 65–121 % at ex vitro (10–61 %), (6–68 %), and proline content decreased, respectively, as compared to NPsS treated seedlings. Malondialdehyde (MDA) level in NPsP seedlings decreased (4–33 %) in ex vitro compared to NPsS seedlings, indicating ROS scavenging and healthy seedling development. In the current study, increased seed germination aided rapid seedling development. Thus, nanoparticles promote seed germination in C. annuum by overcoming the unfavourable effects of reactive oxygen species (ROS) and improving the antioxidative defence system, resulting in increased seedling development.

Mitochondrial dysfunction in acute kidney injury.

Acute kidney injury (AKI) is a systemic clinical syndrome increasing morbidity and mortality worldwide in recent years. Renal tubular epithelial cells (TECs) death caused by mitochondrial dysfunction is one of the pathogeneses. The imbalance of mitochondrial quality control is the main cause of mitochondrial dysfunction. Mitochondrial quality control plays a crucial role in AKI. Mitochondrial quality control mechanisms are involved in regulating mitochondrial integrity and function, including antioxidant defense, mitochondrial quality control, mitochondrial DNA (mtDNA) repair, mitochondrial dynamics, mitophagy, and mitochondrial biogenesis. Currently, many studies have used mitochondrial dysfunction as a targeted therapeutic strategy for AKI. Therefore, this review aims to present the latest research advancements on mitochondrial dysfunction in AKI, providing a valuable reference and theoretical foundation for clinical prevention and treatment of this condition, ultimately enhancing patient prognosis.

Folic acid mitigates the developmental and neurotoxic effects of bisphenol A in zebrafish by inhibiting the oxidative stress/JNK signaling pathway

Bisphenol A (BPA) is a widespread environmental endocrine disruptor (EED) that can cause various environmental and health issues by inducing oxidative stress. The c-Jun N-terminal kinase (JNK) signaling pathway plays a crucial role in oxidative stress-mediated cellular damage. Although folic acid (FA) has demonstrated antioxidant properties, its potential protective effects against BPA-induced developmental and neurotoxicity, as well as the mechanisms involved in the JNK signaling pathway, are still not completely understood. Zebrafish embryos were exposed to different concentrations of BPA ranging from 20 to 40 µM, with or without treatment of 50 µM FA, starting at 6 hours post-fertilization (hpf). Various parameters such as hatchability, survival rate, body length, and heart rate were measured and analyzed. Transcriptome sequencing was conducted to study the changes in gene expression. Oxidative stress markers, including reactive oxygen species (ROS), lipid peroxidation (LPO), hydrogen peroxide (H2O2), and catalase (CAT) activity, were assessed. The expression of proteins related to the mitogen-activated protein kinase (MAPK)/JNK pathway was analyzed using western blot. Neurodevelopmental and apoptotic outcomes were evaluated through behavioral tests, immunofluorescence and RT-qPCR examinations. The study found that exposure to BPA led to a decrease in hatchability, survival, body length, heart rate, total antioxidant capacity and promoted apoptosis in zebrafish larvae. However, supplementation with FA was able to alleviate these negative effects. BPA exposure increased levels of ROS, LPO, and H2O2, while decreasing CAT activity in zebrafish larvae. Treatment with FA effectively reduced BPA-induced oxidative stress and restored antioxidant defense systems. Moreover, KEGG pathway enrichment analysis revealed that the MAPK signaling pathway was the most enriched signaling pathway. Further studies revealed that BPA activated the JNK signaling pathway, while FA suppressed this activation. Additionally, FA significantly improved BPA-induced neurobehavioral deficits and protected against neurocytological alterations. Our findings demonstrate that FA effectively protects against BPA-induced developmental and neurotoxic effects in zebrafish by suppressing oxidative stress and inhibiting the JNK signaling pathway. This study provides new strategies and insights for preventing BPA-induced developmental and neurotoxicity in aquatic organisms.

Polysaccharides from Ziziphus jujuba prolong lifespan and attenuate oxidative stress in Caenorhabditis elegans via DAF-16 and SKN-1

Jujube is a commonly consumed traditional Chinese medicine (TCM) food-drug interaction. Recent evidence revealed crude polysaccharides of jujube extract (CPJE) exhibited bioactive properties in vitro; however, its antioxidant capacity in vivo remains unknown. The objectives of this study were to evaluate the effects of CPJE on growth, locomotion, reproduction, lifespan, and antioxidant defense system using Caenorhabditis elegans. Results showed CPJE were not toxic to C. elegans with no effects on bacterial growth. Compared to control, CPJE significantly increased body length and width, head thrashes, body bends, and brood size of nematodes. In addition, CPJE at higher concentrations significantly increased pharyngeal pumping of the nematodes. Moreover, CPJE at 0.25, 0.5, and 1 mg/mL promoted lifespan by 17.9 %, 34.7 % and 46.3 %, respectively. CPJE at higher concentrations reduced level of ROS, increased activities of SOD, CAT, and GSH. CPJE also upregulated the expression of daf-16, skn-1, sod-3, and gcs-1 in N2 nematodes. Meanwhile, results from studies with nematode mutants also suggested that improved stress resistance of CPJE was due to modulation of daf-16 and skn-1. Overall, our results suggest CPJE promote longevity and reduce oxidative stress via DAF-16 and SKN-1. Our findings shed a new light on the utilization of CPJE to attenuate oxidative stress.

Comparative Study of Human Serum Paraoxonase-1 (PON-1) Activity in Type 2 Diabetes Mellitus: Insights into Oxidative Stress and Antioxidant Defence

Diabetes mellitus is a disease characterized by chronic high blood sugar levels resulting from defects in insulin secretion, insulin action, or both. Prolonged high blood glucose can increase production of reactive oxygen species, leading to elevated oxidative stress. The enzyme paraoxonase-1 (PON1), made in the liver and transported on high-density lipoprotein (HDL), acts as an antioxidant and can counter oxidative stress. This study aimed to compare PON1 activity between healthy controls, obese type 2 diabetics, and non-obese type 2 diabetics. There were 30 healthy controls, 30 obese type 2 diabetics (group I), and 30 non-obese type. Additionally, fasting lipid profiles, fasting plasma glucose, uric acid, albumin, and total bilirubin levels were determined using a clinical chemistry analyzer. The goal was to evaluate differences in PON1 activity as well as metabolic parameters between the three study groups. The results In comparison to the healthy control group, the diabetes group had Significantly higher blood sugar, serum cholesterol, serum triglycerides, serum LDL, and serum uric acid levels, Compared to the healthy control group, PON was Significantly lower in group II patients, Conclusion that Obese type 2 DM patients had significantly lower PON1 and HDL-C levels, which may indicate That the overweight has lessened biochemical functions for these substances. As dyslipidemia, insulin resistance, and high blood pressure are thought to be crucial factors in the cause of metabolic conditions in obese people, the reduced paraoxonase level may increase their likelihood of developing these conditions.