Antioxidant Defense Pathways Research Articles

The Potential Protective Mechanisms of Exercise-Responsive Molecules in Chronic Kidney Disease

PURPOSE: Chronic kidney disease (CKD) is a major global health issue characterized by a gradual and irreversible decline in renal function. Despite its increasing prevalence, effective therapeutic options remain limited, highlighting the need for novel treatment approaches. This review highlights the importance of exercise as a nonpharmacological intervention by exploring the role of exerciseinduced bioactive molecules in CKD management.METHODS: An extensive literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar. The search terms included “myokine,” “exerkine,” “chronic kidney disease,” “nephropathy,” “renal function,” “podocyte,” “mesangial cell,” “exercise,” “physical activity,” and other related terms.RESULTS: Exercise-induced molecules, particularly myokines and exerkines, can slow the progression of CKD through protective mechanisms. These molecules reduce oxidative stress via antioxidant defense pathways, regulate immune responses to limit inflammation, and inhibit fibrotic signaling by interacting with TGF-β and other pro-fibrotic factors. Furthermore, they preserve renal function by maintaining podocyte and mesangial cell integrity and modulating autophagy, thereby preventing kidney damage.CONCLUSIONS: This review consolidates the current knowledge on the therapeutic potential and diverse functions of exercise-induced molecules in CKD, offering insights into their ability to slow disease progression and improve patient outcomes through nonpharmacological strategies.

Antiaging in a Bottle: Bioactive Competency of Plasma-Generated Nitric Oxide Water for Modulation of Aging-Related Signature in Human Dermal Cells.

Nitric oxide (NO), a potential therapeutic antiaging molecule, modulates various physiological and cellular processes. However, alterations in endogenous NO levels brought on by aging impact multiple organ systems and heighten susceptibility to age-related skin diseases. This correlation underscores the importance of investigating NO-based antiaging interventions. Nonthermal plasma-generated NO is a promising avenue for cosmetic and regenerative medicine due to its capacity to stimulate cellular growth. Herein, we examine the potential of plasma-generated nitric oxide water (NOW) as a bioactive agent in human dermal fibroblasts, emphasizing gene expression patterns linked to extracellular matrix (ECM) breakdown and cellular senescence. The findings of our study indicate that administering NOW at lower dosages enhances cell migration and proliferation. Moreover, the genetic signatures associated with ECM synthesis, antioxidant defense, and antisenescence pathways have been analyzed in NOW-exposed cells. Notably, the downregulation of ECM-degrading enzyme transcripts─collagenase, elastase, and hyaluronidase─suggests NOW's potential in mitigating the intrinsic skin aging phenomena, emphasizing the promise of NO-based interventions in advancing antiaging strategies within regenerative medicine.

Toxic Effect of Methyl-Thiophanate on Bombyx mori Based on Physiological and Transcriptomic Analysis

Background/Objectives: The utilization of methyl-thiophanate (MT) in vegetables and fruits is widespread due to its broad efficiency, yet its potential impact on silkworm growth remains uncertain. This study aims to examine the effects of MT on the growth of silkworms. Specifically, we assessed the weights of fifth-instar larvae that were fed mulberry leaves saturated with three concentrations (2.5, 5, and 10 mg/mL) of MT, as well as the weights of a control group. Methods: TEM was used to show the status of the silkworm midgut after MT supplementation. Oxidative stress was evaluated in the presence of MT. Furthermore, a transcriptomic sequencing experiment was conducted to investigate the mechanism through which the development of silkworms is induced by MT. Results: Our findings indicate that the supplementation of MT hindered larval growth compared to the control group, suggesting a toxic effect of MT on silkworms. The transmission electron microscopy (TEM) results show that MT supplementation induced autophagy in the silkworm midgut. MT was also found to induce oxidative stress in silkworms through the activation of reactive oxygen (ROS), superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities. Subsequent transcriptomic analysis revealed 1265 significantly differentially expressed genes (DEGs) in response to MT. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these DEGs were associated with antioxidant defense, detoxification processes, lysosome biogenesis, and metabolic pathways. Conclusions: These findings suggest that MT toxicity in silkworm larvae is mediated through the induction of oxidative stress and alterations in metabolism. This study contributes to our understanding of the impacts of MT exposure on silkworms and provides insights into potential pesticides for use in mulberry gardens.

DbGTi protein attenuates chromium (VI)-induced oxidative stress via activation of the Nrf2/HO-1 signalling pathway in zebrafish (Danio rerio) larval model

Hexavalent chromium (Cr (VI)) contamination poses a significant threat to environmental and human health due to its ability to induce oxidative stress. Conventional strategies to counter Cr (VI)-induced oxidative stress, like antioxidants and chelating agents, face efficacy limitations and adverse effects. The present study is intended to counteract the limitations of conventional strategies by introducing a trypsin inhibitor isolated from Dioscorea bulbifera L. tubers, known as DbGTi protein, against Cr (VI)-induced developmental toxicity and oxidative stress. Through a comprehensive array of biochemical assays, behavioural tests, and gene expression analyses, this study interprets the underlying mechanisms of the DbGTi protein. Results demonstrated that the DbGTi protein effectively restored antioxidant defense systems, including superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione S-transferase (GST), and glutathione peroxidase (GTPx), thereby mitigating cellular damage, reducing cell death, and enhancing neuro-biomarkers. qRT-PCR analysis of mRNA expression profiling revealed the upregulation of genes associated with antioxidant defense (sod, cat, gpx) and defense pathway (nrf2, hmox-1a), further highlighting the protective effects of DbGTi protein against Cr (VI)-induced oxidative stress.

Unraveling the mechanisms of biochar and steel slag in alleviating lithium stress in tomato (Solanum lycopersicum L.) plants via modulation of antioxidant defense and methylglyoxal detoxification pathways

With progress in technology, soaring demand for lithium (Li) has led to its release into the environment. This study demonstrated the mitigation of the adverse effects of Li stress on tomato (Solanum lycopersicum L.) by the application of waste materials, namely coconut shell biochar (CBC) and steel slag (SS). To explore the impact of Li treatment on tomato plants different morphological, biochemical parameters and plant defense system were analyzed. Tomato plants exposed to Li had shorter roots and shoots, lower biomass and relative water contents, and showed decreases in physiological variables, as well as increases in electrolyte leakage and lipid peroxidation. However, the application of CBC and SS as passivators, either singly or in combination, increased growth variables of tomato and relieved Li-induced oxidative stress responses. The combined CBC and SS amendments reduced Li accumulation 82 and 90% in tomato roots and shoots, respectively, thereby minimizing the negative impacts of Li. Antioxidant enzymes SOD, CAT, APX and GR reflected 4, 5, 30, and 52% and glyoxalase enzymes I and II 7 and 250% enhancement in presence of both CBC and SS in Li treated soil, with a concurrent decrease in methylglyoxal content. Lithium treatment triggered oxidative stress, increased enzymatic and non-enzymatic antioxidant levels, and induced the synthesis of thiols and phytochelatins in roots and shoots. Hence, co-amendment with CBC and SS protected tomato plants from Li-induced oxidative damage by increasing antioxidant defenses and glyoxalase system activity. Both CBC, generated from agricultural waste, and SS, an industrial waste, are environmentally benign, safe, economical, and non-hazardous materials that can be easily applied on a large scale for crop production in Li-polluted soils. The present findings highlight the novel reutilization of waste materials as renewable assets to overcome soil Li problems and emphasize the conversion of waste into wealth and its potential for practical applications.

ZmASR1 negatively regulates drought stress tolerance in maize

Abscisic acid-, stress-, and ripening-induced (ASR) proteins in plants play a significant role in plant response to diverse abiotic stresses. However, the functions of ASR genes in maize remain unclear. In the present study, we identified a novel drought-induced ASR gene in maize (ZmASR1) and functionally characterized its role in mediating drought tolerance. The transcription of ZmASR1 was upregulated under drought stress and abscisic acid (ABA) treatment, and the ZmASR1 protein was observed to exhibit nuclear and cytoplasmic localization. Moreover, ZmASR1 knockout lines generated with the CRISPR–Cas9 system showed lower ROS accumulation, higher ABA content, and a higher degree of stomatal closure than wild-type plants, leading to higher drought tolerance. Transcriptome sequencing data indicated that the significantly differentially expressed genes in the drought treatment group were mainly enriched in ABA signal transduction, antioxidant defense, and photosynthetic pathway. Taken together, the findings suggest that ZmASR1 negatively regulates drought tolerance and represents a candidate gene for genetic manipulation of drought resistance in maize.

Cullin 3 RING E3 ligase inactivation causes NRF2-dependent NADH reductive stress, hepatic lipodystrophy, and systemic insulin resistance

Cullin RING E3 ligases (CRL) have emerged as key regulators of disease-modifying pathways and therapeutic targets. Cullin3 (Cul3)-containing CRL (CRL3) has been implicated in regulating hepatic insulin and oxidative stress signaling. However, CRL3 function in liver pathophysiology is poorly defined. Here, we report that hepatocyte Cul3 knockout results in rapid resolution of steatosis in obese mice. However, the remarkable resistance of hepatocyte Cul3 knockout mice to developing steatosis does not lead to overall metabolic improvement but causes systemic metabolic disturbances. Liver transcriptomics analysis identifies that CRL3 inactivation causes persistent activation of the nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant defense pathway, which also reprograms the lipid transcriptional network to prevent TG storage. Furthermore, global metabolomics reveals that NRF2 activation induces numerous NAD+-consuming aldehyde dehydrogenases to increase the cellular NADH/NAD+ ratio, a redox imbalance termed NADH reductive stress that inhibits the glycolysis-citrate-lipogenesis axis in Cul3 knockout livers. As a result, this NRF2-induced cellular lipid storage defect promotes hepatic ceramide accumulation, elevates circulating fatty acids, and worsens systemic insulin resistance in a vicious cycle. Hepatic lipid accumulation is restored, and liver injury and hyperglycemia are attenuated when NRF2 activation and NADH reductive stress are abolished in hepatocyte Cul3/Nrf2 double-knockout mice. The resistance to hepatic steatosis, hyperglycemia, and NADH reductive stress are observed in hepatocyte Keap1 knockout mice with NRF2 activation. In summary, our study defines a critical role of CRL3 in hepatic metabolic regulation and demonstrates that the CRL3 downstream NRF2 overactivation causes hepatic metabolic maladaptation to obesity and insulin resistance.

Porcine Brain Enzyme Hydrolysate Enhances Immune Function and Antioxidant Defense via Modulation of Gut Microbiota in a Cyclophosphamide-Induced Immunodeficiency Model.

This study examined how consuming porcine brain enzyme hydrolysate (PBEH) affects the immune function and composition of the gut microbiota in an immunodeficient animal model. Male Wistar rats aged 6 weeks were fed casein (control), 100 mg/kg body weight (BW), red ginseng extract (positive-control), and 6, 13, and 26 mg PBEH per kg BW (PBEH-L, PBEH-M, and PBEH-H, respectively) daily for 4 weeks. At 30 min after consuming assigned compounds, they were orally administered cyclophosphamide (CTX; 5 mg/kg BW), an immunosuppressive agent, to suppress the immune system by inhibiting the proliferation of lymphocytes. The normal-control rats were fed casein and water instead of CTX. Natural killer cell activity and splenocyte proliferation induced by 1 μg/mL lipopolysaccharide were lower in the control group than the normal-control group, and they significantly increased with PBEH consumption, particularly at high doses. The PBEH consumption increased dose-dependently in the Th1/Th2 ratio compared to the control. The lipid peroxide contents were lower in the PBEH group than in the control group. Moreover, PBEH m and PBEH-H consumption mitigated white pulp cell damage, reduced red pulp congestion, and increased spleen mast cells in the histological analysis. Intestinal microbiota composition demonstrated differences between the groups at the genus levels, with Akkermansia being more abundant in the control group than the normal-control group and the PBEH-H group showing a decrease. However, Bifidobacterium decreased in the control group but increased in the PBEH-H group. The β-diversity revealed distinct microbial communities of PBEH and positive-control groups compared to the control group (p < 0.05). The metagenome predictions revealed that PBEH-H influenced amino acid metabolism, antioxidant defense, insulin sensitivity, and longevity pathways. In conclusion, PBEH-H intake boosted immune responses and reduced lipid peroxides by modulating gut microbiota composition. These findings suggest that PBEH-H has the potential as a dietary supplement for improving immune function and gut health in individuals with immunodeficiency.

The role and therapeutic potential of SIRTs in sepsis.

Sepsis is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection. Abnormal activation of the immune system and disturbance of energy metabolism play a key role in the development of sepsis. In recent years, the Sirtuins (SIRTs) family has been found to play an important role in the pathogenesis of sepsis. SIRTs, as a class of histone deacetylases (HDACs), are widely involved in cellular inflammation regulation, energy metabolism and oxidative stress. The effects of SIRTs on immune cells are mainly reflected in the regulation of inflammatory pathways. This regulation helps balance the inflammatory response and may lessen cell damage and organ dysfunction in sepsis. In terms of energy metabolism, SIRTs can play a role in immunophenotypic transformation by regulating cell metabolism, improve mitochondrial function, increase energy production, and maintain cell energy balance. SIRTs also regulate the production of reactive oxygen species (ROS), protecting cells from oxidative stress damage by activating antioxidant defense pathways and maintaining a balance between oxidants and reducing agents. Current studies have shown that several potential drugs, such as Resveratrol and melatonin, can enhance the activity of SIRT. It can help to reduce inflammatory response, improve energy metabolism and reduce oxidative stress, showing potential clinical application prospects for the treatment of sepsis. This review focuses on the regulation of SIRT on inflammatory response, energy metabolism and oxidative stress of immune cells, as well as its important influence on multiple organ dysfunction in sepsis, and discusses and summarizes the effects of related drugs and compounds on reducing multiple organ damage in sepsis through the pathway involving SIRTs. SIRTs may become a new target for the treatment of sepsis and its resulting organ dysfunction, providing new ideas and possibilities for the treatment of this life-threatening disease.

Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production and elimination is termed oxidative stress, a critical factor and common denominator of many chronic diseases such as cancer, cardiovascular diseases, metabolic diseases, neurological disorders (Alzheimer's and Parkinson's diseases), and other disorders. To counteract the harmful effects of ROS, organisms have evolved a complex, three-line antioxidant defense system. The first-line defense mechanism is the most efficient and involves antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). This line of defense plays an irreplaceable role in the dismutation of superoxide radicals (O2•-) and hydrogen peroxide (H2O2). The removal of superoxide radicals by SOD prevents the formation of the much more damaging peroxynitrite ONOO- (O2•- + NO• → ONOO-) and maintains the physiologically relevant level of nitric oxide (NO•), an important molecule in neurotransmission, inflammation, and vasodilation. The second-line antioxidant defense pathway involves exogenous diet-derived small-molecule antioxidants. The third-line antioxidant defense is ensured by the repair or removal of oxidized proteins and other biomolecules by a variety of enzyme systems. This review briefly discusses the endogenous (mitochondria, NADPH, xanthine oxidase (XO), Fenton reaction) and exogenous (e.g., smoking, radiation, drugs, pollution) sources of ROS (superoxide radical, hydrogen peroxide, hydroxyl radical, peroxyl radical, hypochlorous acid, peroxynitrite). Attention has been given to the first-line antioxidant defense system provided by SOD, CAT, and GPx. The chemical and molecular mechanisms of antioxidant enzymes, enzyme-related diseases (cancer, cardiovascular, lung, metabolic, and neurological diseases), and the role of enzymes (e.g., GPx4) in cellular processes such as ferroptosis are discussed. Potential therapeutic applications of enzyme mimics and recent progress in metal-based (copper, iron, cobalt, molybdenum, cerium) and nonmetal (carbon)-based nanomaterials with enzyme-like activities (nanozymes) are also discussed. Moreover, attention has been given to the mechanisms of action of low-molecular-weight antioxidants (vitamin C (ascorbate), vitamin E (alpha-tocopherol), carotenoids(e.g., β-carotene, lycopene, lutein), flavonoids(e.g.,quercetin, anthocyanins, epicatechin), and glutathione (GSH)), the activation of transcription factors such as Nrf2, and the protection against chronic diseases. Given that there is a discrepancy between preclinical and clinical studies, approaches that may result in greater pharmacological and clinical success of low-molecular-weight antioxidant therapies are also subject to discussion.

Caspase-2 protects against ferroptotic cell death

Caspase-2, one of the most evolutionarily conserved members of the caspase family, is an important regulator of the cellular response to oxidative stress. Given that ferroptosis is suppressed by antioxidant defense pathways, such as that involving selenoenzyme glutathione peroxidase 4 (GPX4), we hypothesized that caspase-2 may play a role in regulating ferroptosis. This study provides the first demonstration of an important and unprecedented function of caspase-2 in protecting cancer cells from undergoing ferroptotic cell death. Specifically, we show that depletion of caspase-2 leads to the downregulation of stress response genes including SESN2, HMOX1, SLC7A11, and sensitizes mutant-p53 cancer cells to cell death induced by various ferroptosis-inducing compounds. Importantly, the canonical catalytic activity of caspase-2 is not required for its role and suggests that caspase-2 regulates ferroptosis via non-proteolytic interaction with other proteins. Using an unbiased BioID proteomics screen, we identified novel caspase-2 interacting proteins (including heat shock proteins and co-chaperones) that regulate cellular responses to stress. Finally, we demonstrate that caspase-2 limits chaperone-mediated autophagic degradation of GPX4 to promote the survival of mutant-p53 cancer cells. In conclusion, we document a novel role for caspase-2 as a negative regulator of ferroptosis in cells with mutant p53. Our results provide evidence for a novel function of caspase-2 in cell death regulation and open potential new avenues to exploit ferroptosis in cancer therapy.

Antioxidant Systems as Modulators of Ferroptosis: Focus on Transcription Factors.

Ferroptosis is a type of programmed cell death that differs from apoptosis, autophagy, and necrosis and is related to several physio-pathological processes, including tumorigenesis, neurodegeneration, senescence, blood diseases, kidney disorders, and ischemia-reperfusion injuries. Ferroptosis is linked to iron accumulation, eliciting dysfunction of antioxidant systems, which favor the production of lipid peroxides, cell membrane damage, and ultimately, cell death. Thus, signaling pathways evoking ferroptosis are strongly associated with those protecting cells against iron excess and/or lipid-derived ROS. Here, we discuss the interaction between the metabolic pathways of ferroptosis and antioxidant systems, with a particular focus on transcription factors implicated in the regulation of ferroptosis, either as triggers of lipid peroxidation or as ferroptosis antioxidant defense pathways.

Partial Chemical Characterization of Drought-Related Metabolites in Maize Under Drought Stress Conditions

This study investigates the metabolic response of maize genotypes UASBM13 (drought-tolerant) and UASBM10 (drought-sensitive) to drought stress using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Drought stress significantly impacts crop productivity, with potential consequences for global food security. Secondary metabolites produced by maize under drought conditions, provide insights into molecular response. The identified metabolites include sinapic acid, sinapoyl malate, coumaroyl shikimate, caffeoyl shikimate, syriogenin, sinapaldehyde, hydroxy ferulate, naringenin chalcone, and resveratrol. These compounds play crucial roles in antioxidant defence, lignification, and stress-related pathways. The results suggest that UASBM13 exhibits a more robust metabolic response to drought, with higher levels of key metabolites associated with stress tolerance. The findings contribute to our understanding of plant adaptation to environmental stress and provide valuable information for developing drought-tolerant crop varieties to ensure global food security in the context of a changing climate and growing population.

The role of ferroptosis in cardio-oncology.

With the rapid development of new generations of antitumor therapies, the average survival time of cancer patients is expected to be continuously prolonged. However, these therapies often lead to cardiotoxicity, resulting in a growing number of tumor survivors with cardiovascular disease. Therefore, a new interdisciplinary subspecialty called "cardio-oncology"has emerged, aiming to detect and treat cardiovascular diseases associated with tumors and antitumor therapies. Recent studies have highlighted the role of ferroptosis in both cardiovascular and neoplastic diseases. The balance between intracellular oxidative stress and antioxidant defense is crucial in regulating ferroptosis. Tumor cells can evade ferroptosis by upregulating multiple antioxidant defense pathways, while many antitumor therapies rely on downregulating antioxidant defense and promoting ferroptosis in cancer cells. Unfortunately, these ferroptosis-inducing antitumor therapies often lack tissue specificity and can also cause injury to the heart, resulting in ferroptosis-induced cardiotoxicity. A range of cardioprotective agents exert cardioprotective effects by inhibiting ferroptosis. However, these cardioprotective agents might diminish the efficacy of antitumor treatment due to their antiferroptotic effects. Most current research on ferroptosis only focuses on either tumor treatment or heart protection but rarely considers both in concert. Therefore, further research is needed to study how to protect the heart during antitumor therapies by regulating ferroptosis. In this review, we summarized the role of ferroptosis in the treatment of neoplastic diseases and cardiovascular diseases and also attempted to propose further research directions for ferroptosis in the field of cardio-oncology.

Resveratrol improves meat quality traits by activating the lncRNAs-KEAP1-NRF2 axis in pigs

This research aims at uncovering the effects and investigating the molecular mechanisms of dietary resveratrol (RES) supplementation on antioxidant capacity and meat quality of pigs. In this study, 20 μM RES could activate the KEAP1-NRF2 antioxidant defense pathway in response to oxidative stress in porcine skeletal muscle satellite cells was firstly found. Then, twenty-four healthy crossbred castrated boars were allocated to 4 treatments that were fed with a basal diet (control) and a basal diet supplemented with 200 mg, 400 mg or 600 mg RES per Kilogram (kg) of feed for 41 days, respectively. 400 and 600 mg/kg RES-supplemented diet can effectively improve the meat quality traits and activities of antioxidizing enzymes via the KEAP1–NRF2 signaling pathway of pigs. The molecular dynamic simulation further revealed that RES could directly binding to KEAP1 to reduce the tightness of KEAP1–NRF2 protein-protein interaction. More importantly, dietary supplementation of RES also improves antioxidant capacity through a series of KEAP1–NRF2 pathway-related lncRNAs were found by RNA sequencing (RNA-seq). Altogether, this study demonstrated that RES improves meat quality traits by effectively increasing antioxidant levels via the lncRNA-KEAP1–NRF2 axis in vivo and/or in vitro. These results provide new insights into the molecular mechanisms by which RES, as a nutritional agent, regulates antioxidant capacity and improves meat quality in pigs.

Modulation of the immune response by the host defense peptide IDR-1002 in chicken hepatic cell culture

IDR-1002, a synthetic host defense peptide (HDP), appears to be a potential candidate for the treatment of bacterial infections and the consequent inflammatory response due to its potent immunomodulatory activity. This is of relevance to the emerging issue of antimicrobial resistance in the farming sector. In this study, the effects of IDR-1002 were investigated on a chicken hepatocyte‒non-parenchymal cell co-culture, and the results revealed that IDR-1002 had complex effects on the regulation of the hepatic innate immunity. IDR-1002 increased the levels of both RANTES (Regulated on Activation, Normal T cell Expressed and Secreted) and Macrophage colony stimulating factor (M-CSF), suggesting the peptide plays a role in the modulation of macrophage differentiation, also reflected by the reduced concentrations of interleukin (IL)-6 and IL-10. The pro-inflammatory cytokine release triggered by the bacterial cell wall component lipoteichoic acid (LTA) was ameliorated by the concomitantly applied IDR-1002 based on the levels of IL-6, chicken chemotactic and angiogenic factor (CXCLi2) and interferon (IFN)-γ. Moreover, the production of nuclear factor erythroid 2-related factor 2 (Nrf2), an essential transcription factor in the antioxidant defense pathway, was increased after IDR-1002 exposure, while protein carbonyl (PC) levels were also elevated. These findings suggest that IDR-1002 affects the interplay of the cellular immune response and redox homeostasis, thus the peptide represents a promising tool in the treatment of bacterially induced inflammation in chickens.

Glucosinolate-rich broccoli sprouts protect against oxidative stress and improve adaptations to intense exercise training

Oxidative stress plays a vital role for the adaptive responses to physical training. However, excessive oxidative stress can precipitate cellular damage, necessitating protective mechanisms to mitigate this effect. Glucosinolates, found predominantly in cruciferous vegetables, can be converted into isothiocyanates, known for their antioxidative properties. These compounds activate crucial antioxidant defence pathways and support mitochondrial function and protein integrity under oxidative stress, in both Nrf2-dependent and independent manners. We here administered glucosinolate-rich broccoli sprouts (GRS), in a randomized double-blinded cross-over fashion to 9 healthy subjects in combination with daily intense exercise training for 7 days. We found that exercise in combination with GRS significantly decreased the levels of carbonylated proteins in skeletal muscle and the release of myeloperoxidase into blood. Moreover, it lowered lactate accumulation during submaximal exercise, and attenuated the severe nocturnal hypoglycaemic episodes seen during the placebo condition. Furthermore, GRS in combination with exercise improved physical performance, which was unchanged in the placebo condition.

Hydroxycitric acid prevents hyperoxaluric-induced nephrolithiasis and oxidative stress via activation of the Nrf2/Keap1 signaling pathway

ABSTRACT Nephrolithiasis is a common and frequently-occurring disease in the urinary system with high recurrence. The present study aimed to explore the protective effect and underlying mechanism of hydroxycitric acid (HCA) in hyperoxaluria-induced nephrolithiasis in vitro and in vivo. Crystal deposition and pathophysiological injury in rat models of glyoxylate-induced nephrolithiasis were examined using H&E staining. Cell models of nephrolithiasis were established by oxalate-treated renal tubular epithelial cells. The levels of oxidative stress indexes were determined by ELISA kits. Cell proliferation in vivo and in vitro was evaluated using a cell counting kit-8 (CCK-8) assay and Ki-67 cell proliferation detection kit. Cell apoptosis was measured by flow cytometry and TUNEL staining. The protein levels were examined by western blotting. Our results showed that HCA administration significantly reduced crystal deposition and kidney injury induced by glyoxylate. HCA also alleviated oxidative stress via upregulating the antioxidant enzyme activities of superoxide dismutase (SOD) and catalase (CAT) and reducing the malondialdehyde (MDA) content. Moreover, HCA treatment promoted cell proliferation and inhibited apoptosis of renal tubular epithelial cells exposed to hyperoxaluria. Of note, Nrf2 activator dimethyl fumarate (DMF) exerted the same beneficial effects as HCA in nephrolithiasis. Mechanistically, HCA prevented crystal deposition and oxidative stress induced by hyperoxaluria through targeting the Nrf2/Keap1 antioxidant defense pathway, while knockdown of Nrf2 significantly abrogated these effects. Taken together, HCA exhibited antioxidation and anti-apoptosis activities in nephrolithiasis induced by hyperoxaluria via activating Nrf2/Keap1 pathway, suggesting that it may be an effective therapeutic agent for the prevention and treatment of nephrolithiasis.

The Biosynthesis, Mechanism of Action, and Physiological Functions of Melatonin in Horticultural Plants: A Review

Melatonin, a hormone known for its role in regulating sleep–wake cycles in mammals, has been found to have diverse functions in horticultural plants. In recent years, research has revealed the involvement of melatonin in various physiological processes in plants, like regulation of growth and development, stress tolerance, and antioxidant defense. Melatonin can augment seed germination, roots, shoot growth, and biomass accumulation in horticultural crops. It also performs a vital role in regulating vegetative and reproductive growth stages, floral transition, and leaf senescence. Melatonin improves stress tolerance in crops by regulating root architecture, nutrient uptake, and ion transport. Additionally, melatonin works like a broad-spectrum antioxidant by scavenging reactive oxygen species and enhancing antioxidant activity. The mechanism of action of melatonin in horticultural plants involves gene expressions, hormone signaling pathways, and antioxidant defense pathways. Melatonin also interacts with other plant growth regulators (PGRs), comprising auxins, cytokinins, and abscisic acid to coordinate various physiological processes in plants. Melatonin has evolved as a versatile chemical entity with diverse functions in horticultural plants, and its potential applications in crop production and stress management are increasingly being explored. This review aims to provide a comprehensive insight into the present state of knowledge about melatonin and its role in horticulturally important plants and identify avenues for further research and practical applications. Further study must be conducted to fully elucidate the mechanisms of melatonin action in crops and to outline effective strategies for its practical use in horticultural practices.

Acetate alleviates As toxicity via improving ROS metabolism and antioxidant defense system in lentil seedlings

Arsenic (As) is a toxic element which entries the food chain from the soil through plants and poses a great threat to human health. Also, an excess of As causes adverse physiological and biochemical changes in plants. In the present study, the mechanism of As tolerance in acetate-treated lentil seedlings was investigated. Six-day-old seedlings pretreated with or without 10 mM Na-acetate were exposed to two levels of sodium arsenate (250 and 320 µM) for four days. The results showed that both levels of As caused severe chlorosis, growth reduction, and water imbalance. Furthermore, As-induced oxidative damage in the plants was manifested by higher malondialdehyde and, hydrogen peroxide content, electrolyte leakage, and disruption of the antioxidant defense pathway. However, acetate pretreatment improved growth and chlorophyll content, and reduced oxidative damage by upregulating some components (catalase and ascorbate) of the antioxidant defense pathway in the seedlings. Under As stress, accumulation of As was found in both roots and shoot of lentil. However, acetate pretreatment reduced As accumulation in the roots and inhibited the transfer of As to the shoots in the seedlings. Taken together, the results suggest that acetate can enhance tolerance against As toxicity in lentil seedlings by reducing As accumulation and increasing ROS detoxification through the antioxidant defense pathway.