Antioxidants最新文献

Hair graying is one of the common visible signs of human aging, resulting from decreased or abolished melanogenesis due to the depletion of melanocyte stem cells through excess accumulation of oxidative stress. Cell-free therapy using a conditioned medium (CM) of mesenchymal stem cells has been highlighted in the field of regenerative medicine owing to its potent therapeutic effects with lower regulatory hurdles and safety risk. Recently, we demonstrated that a CM of an immortalized stem cell line from human exfoliated deciduous teeth (SHED) has protective effects against a mouse model of ulcer formation via antioxidative and angiogenic activities mediated by HGF and VEGF. However, to date, no effective treatments for hair graying have been developed, and the effect of SHED-CM on hair graying remains unknown. In this study, we have investigated the effect of SHED-CM on a hair graying mouse model caused by X-ray irradiation. Repetitive subcutaneous administrations of SHED-CM greatly suppressed the development of hair graying, when compared to control medium, resulting in reduced cutaneous expression of 8-hydroxy-2'-deoxyguanosine, the major product of DNA damage induced by reactive oxygen species. Consistent with these in vivo results, SHED-CM significantly inhibited the cell death caused by X-ray irradiation in melanoma cell line B16F10 cells. Immunodepletion of HGF or VEGF in the SHED-CM revealed that this inhibition was due to suppression of the generation of reactive oxygen species, which was mainly mediated by HGF and probably VEGF. These results suggest that SHED-CM has protective effects against hair graying via its antioxidative activity.

The study of mitochondrial dysfunction has become increasingly pivotal in elucidating the pathophysiology of various cerebral pathologies, particularly neurodegenerative disorders. Mitochondria are essential for cellular energy metabolism, regulation of reactive oxygen species (ROS), calcium homeostasis, and the execution of apoptotic processes. Disruptions in mitochondrial function, driven by factors such as oxidative stress, excitotoxicity, and altered ion balance, lead to neuronal death and contribute to cognitive impairments in several brain diseases. Mitochondrial dysfunction can arise from genetic mutations, ischemic events, hypoxia, and other environmental factors. This article highlights the critical role of mitochondrial dysfunction in the progression of neurodegenerative diseases and discusses the need for targeted therapeutic strategies to attenuate cellular damage, restore mitochondrial function, and enhance neuroprotection.

Maternal obesity is increasingly recognized as a risk factor for adverse fetal outcomes, primarily through its association with heightened oxidative stress. This study aimed to evaluate oxidative stress markers in umbilical cord blood of neonates born to obese mothers. Sixty-three pregnant women, who were of normal weight at the start of pregnancy but classified as obese at term, were included. Umbilical cord blood samples were collected immediately post-delivery and analyzed for serum oxidative stress markers (total oxidant status (TOS), total antioxidant status (TAS), paraoxanase (PON), aryl esterase, thiol, and catalase activities). Protein interaction networks were generated using Cytoscape (v3.10.3), and the overlapping proteins were further analyzed for functional annotations with ShinyGO (0.80). The top ten significantly enriched pathways were identified with a false discovery rate (FDR) threshold of <0.05. Significant associations were found between maternal BMI change and paraoxonase 1 (PON1) levels in umbilical cord blood, while no correlation was observed with other oxidative (total oxidant status) and antioxidant markers (total antioxidant status, aryl esterase, thiol, and catalase). Additionally, the correlation analysis showed a significant relationship between BMI change and fetal gestational age, but not with other demographic or clinical features. A total of 24 common protein interactors associated with PON1, obesity, and oxidative stress were identified. Functional annotation analysis revealed significant enrichment in antioxidant and oxidoreductase activities, along with pathways involved in insulin resistance, AGE-RAGE signaling, and atherosclerosis. Maternal obesity may specifically affect PON1 activity, potentially serving as a compensatory response to oxidative stress in neonates, suggesting PON1 as a possible biomarker for oxidative stress-related metabolic disturbances in neonates of obese mothers, with implications for monitoring and managing pregnancy outcomes in obese populations.

Breast cancer is one of the most prevalent cancers worldwide. Recent studies have increasingly emphasized the role of oxidative stress in the initiation and progression of breast cancer. This article reviews how oxidative stress imbalance influences the occurrence and advancement of breast cancer, elucidating the intricate mechanisms through which reactive oxygen species (ROS) operate in this context and their potential therapeutic applications. By highlighting these critical insights, this review aims to enhance our understanding of oxidative stress as a potential target for innovative therapeutic strategies in the management of breast cancer.

Liver cancer is one of the most prevalent cancers worldwide. The first-line therapeutic drug sorafenib offers only a moderate improvement in patients' conditions. Therefore, an approach to enhancing its therapeutic efficacy is urgently needed. It has been revealed that hepatocellular carcinoma (HCC) cells with heightened intracellular quiescin sulfhydryl oxidase 1 (QSOX1) exhibit increased sensitivity to sorafenib. QSOX1 is a secreted disulfide catalyst, and it is widely recognized that extracellular QSOX1 promotes the growth, invasion, and metastasis of cancer cells through its participation in the establishment of extracellular matrix. Inhibiting QSOX1 secretion can increase intracellular QSOX1 and decrease extracellular QSOX1. Such an approach would sensitize HCC cells to sorafenib but remains to be established. Since (-)-epigallocatechin-3-gallate (EGCG) has been demonstrated to be an effective inhibitor of α-fetal protein secretion from HCC cells, we screened QSOX1 secretion inhibition using polyphenolic compounds. We examined eight dietary polyphenols (EGCG, quercetin, fisetin, myricetin, caffeic acid, chlorogenic acid, resveratrol, and theaflavin) and found that EGCG and quercetin effectively inhibited QSOX1 secretion from human HCC cells (HepG2 or Huh7), resulting in high intracellular QSOX1 and low extracellular QSOX1. The combination of EGCG or quercetin, both of which change the cellular distribution of QSOX1, with sorafenib, which has no influence on the cellular distribution of QSOX1, exhibited multiple synergistic effects against the HCC cells, including the induction of apoptosis and inhibition of invasion and metastasis. In conclusion, our current results suggest that dietary EGCG and quercetin have the potential to be developed as adjuvants to sorafenib in the treatment of HCC by modulating the cellular distribution of QSOX1.

Reduced glutathione (GSH) is a main nonenzymatic antioxidant, but its effects and underlying mechanisms on growth and intestinal health in weaned piglets still require further assessment. A total of 180 weaned piglets were randomly allotted to 5 groups: a basal diet (CON), and a basal diet supplemented with antibiotic chlortetracycline (ABX), 50 (GSH1), 65 (GSH2), or 100 mg/kg GSH (GSH3). Results revealed that dietary GSH1, GSH2, and ABX improved body weight and the average daily gain of weaned piglets, and ABX decreased albumin content but increased aspartate aminotransferase (AST) activity and the ratio of AST to alanine transaminase levels in plasma. GSH2 significantly decreased glucose content but increased the content of triglyceride and cholesterol in the plasma. Both GSH1 and GSH2 improved the jejunal mucosa architecture (villus height, crypt depth, and the ratio of villus height to crypt depth), tight junction protein (ZO-1 and Occludin), and antioxidant capacity (CAT and MDA), and the effects were superior to ABX. Dietary GSH improved the jejunal barrier by probably inhibiting the myosin light chain kinas pathway to up-regulate the transcript expression of tight junction protein (ZO-1 and Occludin) and Mucins. Through the proteomics analysis of the jejunal mucosa using 4D-DIA, the KEGG pathway enrichment analysis showed that differentiated proteins were significantly enriched in redox homeostasis-related pathways such as glutathione metabolism, cytochrome P450, the reactive oxygen species metabolic pathway, the oxidative phosphorylation pathway, and the phosphatidylinositol 3-kinase-serine/threonine kinase pathway in GSH2 vs. CON and in GSH2 vs. ABX. The results of proteomics and qRT-PCR showed that GSH supplementation might dose-dependently promote growth performance and that it alleviated the weaning stress-induced oxidative injury of the jejunal mucosa in piglets by activating SIRTI and Akt pathways to regulate GPX4, HSP70, FoxO1. Therefore, diets supplemented with 50-65 mg/kg GSH can promote the growth of and relieve intestinal oxidative injury in weaned piglets.

Cellular senescence is a state of permanent cell cycle arrest accompanied by metabolic activity and characteristic phenotypic changes. This process is crucial for developing age-related diseases, where excessive calorie intake accelerates metabolic dysfunction and aging. Overnutrition disturbs key metabolic pathways, including insulin/insulin-like growth factor signaling (IIS), the mammalian target of rapamycin (mTOR), and AMP-activated protein kinase. The dysregulation of these pathways contributes to insulin resistance, impaired autophagy, exacerbated oxidative stress, and mitochondrial dysfunction, further enhancing cellular senescence and systemic metabolic derangements. On the other hand, dysfunctional endothelial cells and adipocytes contribute to systemic inflammation, reduced nitric oxide production, and altered lipid metabolism. Numerous factors, including extracellular vesicles, mediate pathological communication between the vascular system and adipose tissue, amplifying metabolic imbalances. Meanwhile, caloric restriction (CR) emerges as a potent intervention to counteract overnutrition effects, improve mitochondrial function, reduce oxidative stress, and restore metabolic balance. CR modulates pathways such as IIS, mTOR, and sirtuins, enhancing glucose and lipid metabolism, reducing inflammation, and promoting autophagy. CR can extend the health span and mitigate age-related diseases by delaying cellular senescence and improving healthy endothelial-adipocyte interactions. This review highlights the crosstalk between endothelial cells and adipocytes, emphasizing CR potential in counteracting overnutrition-induced senescence and restoring vascular homeostasis.

Dry eye syndrome (DES) is a prevalent ocular condition characterized by tear film instability, inflammation, and discomfort, affecting millions worldwide. DES is related to oxidative stress imbalance and ocular surface inflammation, which are important factors in the development of the condition. Recent studies have demonstrated that fish oil, lutein, and zeaxanthin possess anti-inflammatory and antioxidant properties. This study investigated the efficacy of a multicomponent dietary supplement in improving tear secretion and mitigating ocular surface inflammation in patients with DES. It was an open-label intervention trial. In total, 52 participants were randomly assigned to control (n = 23) and supplement (45 mg/day eicosapentaenoic acid, 30 mg/day docosahexaenoic acid, 30 mg/day lutein, and 1.8 mg/day zeaxanthin; n = 29) groups for 12 weeks. The participants were evaluated using Schirmer's test and the ocular surface disease index (OSDI) as ocular surface parameters. Moreover, blood or tear oxidative stress, antioxidant capacities, and tear inflammatory indicators were measured at weeks 0 and 12. The results indicated a significant increase in tear secretion and a significant reduction in OSDI scores in the supplement group. Additionally, inflammatory markers, such as interleukin (IL)-6 and IL-8, significantly decreased after the intervention. However, the OSDI of the supplement group significantly improved by 6.60 points (β = -6.60, p = 0.01). These findings support the potential of targeted nutritional supplementation as a safe and effective strategy for alleviating DES symptoms, offering an alternative to conventional treatments that exclusively focus on symptom management. This study highlights the role of specific nutrients in modulating tear production and inflammation, thereby providing a foundation for dietary approaches to DES treatment. Future research should explore the long-term benefits of such interventions and their impact on overall ocular health.

Due to oxidative damage and mitochondrial dysfunction, boar semen cryopreservation remains a significant challenge. This study investigates the effects of pyrroloquinoline quinone (PQQ), a mitochondrial-targeted antioxidant, on the post-thaw boar sperm quality during cryopreservation. Boar semen was diluted in a freezing extender containing different concentrations of PQQ (0, 10, 100, 1000, 10,000 nM). After freezing-thawing, the sperm motility, viability, acrosome integrity, mitochondrial activity, adenosine triphosphate (ATP) levels, DNA integrity, malondialdehyde (MDA) levels, reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, mitochondrial transcription proteins levels, and fertilization capacity were assessed. The results show that 1000 nM PQQ supplementation to the freezing extender significantly enhanced post-thaw sperm motility, viability, and acrosome integrity compared to the control (p < 0.05). Additionally, 1000 nM PQQ increased mitochondrial membrane potential (MMP) and ATP levels, while decreasing MDA and mitochondrial ROS levels, and reducing DNA damage (p < 0.05). Furthermore, the levels of mitochondrial-encoded proteins were significantly elevated in the 1000 nM PQQ group compared to the control (p < 0.05). Interestingly, sperm in the 1000 nM PQQ group showed a higher binding rate to oviductal epithelial cells and the zona pellucida (ZP), indicating higher fertilization potential. These findings suggest that the use of mitochondria-target antioxidant, PQQ, can improve post-thaw boar sperm quality and fertilization via its capacity to reduce oxidative stress and protect mitochondrial function.

Chronic kidney disease (CKD) and hypertension are interconnected, worsening each other. Recent studies have shown that the reduction of peroxiredoxin 5 (Prdx5) accelerates kidney fibrosis, a hallmark of CKD. This study aims to observe whether the deficiency of Prdx5 also contributes to the worsening of CKD-related hypertension. Angiotensin II (Ang II, 1000 ng/kg/day) was infused into Prdx5 wild-type (WT) and Prdx5 knock out (KO) mice (each group; n = 6). The blood pressure was higher in the Ang-II-infused Prdx5 KO mice than in the WT mice. Ang-II-induced ROS/RNS generation and fibrotic marker expressions were also higher in the Prdx5 KO mice. In particular, the expression of the sodium-chloride cotransporter (NCC), an ion transport protein important for sodium retention in the distal convoluted tubule, and the NCC's phosphorylation at Thr53 were increased in the kidney of Ang-II-infused Prdx5 KO. The activity of an WNK4-SPAK/OSR1, upstream activator of the NCC, was also increased. In 209/mDCT cells, the knockdown of Prdx5 (siPrdx5) increased the activity of Ang-II-mediated WNK4-SPAK/OSR1-NCC signaling and Ang-II-mediated ROS generation, whereas Prdx5 overexpression showed opposite results. In conclusion, Prdx5 negatively regulates the WNK4-SPAK/OSR1-NCC signaling axis, indicating its potential as a candidate for antihypertensive drug development through NCC regulation.