Antioxidants最新文献

Aging is associated with detrimental bone loss, often leading to fragility fractures, which may be driven by oxidative stress. In this study, the outcomes of comparing the differences among young, adult and aged C57BL/6J mice found that the trabecular bone volume was significantly lower in the aged mice compared to young mice, and the bone characteristics were significantly correlated with the oxidative status. To counteract the adverse effects of aging, methyl sulfonyl methane (MSM), a stable metabolite of dimethyl sulfoxide, was used to supplement the drinking water (400 mg/kg/day) of the aged mice (73 weeks old) for 8 weeks. The MSM supplementation improved the maximum load, bone microarchitecture, and mRNA levels of osteocyte-specific genes in the tibia. Furthermore, MSM reduced the serum level of the C-terminal telopeptide of type I collagen, a marker of bone resorption, and downregulated the mRNA levels of genes related to osteoclast proliferation and activity. MSM also decreased the levels of pro-inflammatory cytokines in both the serum and bone marrow. Importantly, the MSM-treated mice exhibited an enhanced antioxidant status, characterized by increased glutathione peroxidase (GPx) activity and glutathione concentration in plasma, erythrocytes and bone marrow. These improvements were linked to the activation of the nuclear factor E2 related factor 2 (Nrf2) pathway and its downstream antioxidant gene expression, including that of superoxide dismutase and GPx. These findings suggested that age-related bone loss is closely tied to oxidative stress, and MSM supplementation effectively reverses bone loss by mitigating oxidative stress-mediated bone resorption.

Ferroptosis, an iron-dependent form of non-apoptotic cell death, is regulated by a complex network involving lipid metabolism, iron homeostasis, and the oxidative-reductive system, with iron accumulation and lipid peroxidation as key drivers. Mitochondrial dysfunction and ROS overproduction often underlie the pathogenesis of mitochondrial diseases, for which treatment options are limited, emphasizing the need for novel therapies. In this study, we investigated whether polydatin and nicotinamide could reverse ferroptosis-related pathological features in cellular models derived from patients with pathogenic GFM1 variants. Mutant fibroblasts showed increased iron and lipofuscin accumulation, altered expression of iron metabolism-related proteins, elevated lipid peroxidation, and heightened susceptibility to erastin-induced ferroptosis. Treatment with polydatin and nicotinamide effectively corrected these alterations and reduced iron accumulation and lipid peroxidation in induced neurons. Furthermore, chloramphenicol treatment in control cells mimicked the mutant phenotype, suggesting that these pathological changes are linked to the mitochondrial protein synthesis defect characteristic of pathogenic GFM1 variants. Notably, adding vitamin E to the polydatin and nicotinamide co-treatment resulted in a reduction in the minimum effective concentration, suggesting potential benefits of its inclusion. In conclusion, the combination of polydatin, nicotinamide, and vitamin E could represent a promising therapeutic option for patients with mitochondrial disorders caused by pathogenic GFM1 variants.

Skeletal muscle is primarily involved in exercise performance and health promotion. Sulforaphane (SFN) is a naturally occurring isothiocyanate that indirectly activates the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), thus inducing the expression of Nrf2 target genes, including antioxidant enzymes. This study aimed to identify the effects of a single dose of SFN administration on exhaustive exercise-induced inflammation and oxidative stress in skeletal muscle tissue and elucidate the underlying mechanisms. Thirty-six mice were divided into four groups: control, SFN, exercise (Ex), and SFN + Ex. The SFN group and SFN + Ex group received SFN orally (50 mg/kg body weight) 2 h before the running test. Exercise significantly reduced plasma glucose levels, while the SFN-treated group exhibited a smaller reduction. Acute exhaustive exercise increased the expression of pro-inflammatory cytokines in muscle tissue, while the SFN + Ex group exhibited significantly reduced expression of pro-inflammatory cytokines. The gene expression of Nrf2 and its target enzymes, including heme oxygenase (HO)-1, superoxide dismutase (SOD)-1, catalase (CAT), and glutathione peroxidase (GPx)-1, was measured in the gastrocnemius and soleus muscle tissue. Compared with the Ex group, the SFN + Ex group showed upregulated expression of all these parameters, including Nrf2. SFN treatment reduced acute exhaustive exercise-induced oxidative stress and inflammation via activation of the Nrf2/HO-1 signaling pathway.

The term "oxidative stress" refers to an imbalance between reactive oxygen species (ROS) generation and the antioxidant system, resulting in the increased formation of ROS and the reduced and/or inadequate efficiency of the physiological processes responsible for their elimination and homeostasis maintenance [...].

Peyronie's disease (PD) is a chronic disease characterized by the development of fibrous tissue in the tunica albuginea of the penile corpora cavernosa that causes penile deformity. The precise cause of PD is not completely understood, but it is generally believed to be initiated by a specific injury in the affected area. Research has consistently shown that oxidative stress (OS) is a key player in PD. Pentoxifylline (PTX) is a synthetic derivative of methylxanthine that was initially used for the management of peripheral vascular disease. PTX has also been used in humans for several inflammatory and fibrotic conditions, including PD. PTX has several mechanisms of action, including antioxidant, antifibrotic, anti-inflammatory, and vasorelaxant. This article aims to verify, after a review of the literature regarding the use of PTX in PD, whether this substance is really able to cure PD. We conducted research by consulting the scientific literature on the topic. Results: After examining 39 articles, we considered 20 articles eligible for our narrative review, including a single randomized controlled clinical study, six clinical studies with a control group, a single uncontrolled clinical study, eight case report studies, and four systematic review articles. Conclusions: Although the systematic review articles selected in this paper showed no consistent evidence regarding the efficacy of PTX, in our opinion, the clinical studies we have analyzed undoubtedly demonstrate that PTX is able to combat PD, thanks to its ability to interfere with the pathogenic mechanisms of the disease. However, we believe that further new randomized controlled trials are necessary to more clearly demonstrate the effectiveness of PTX in the treatment of PD.

Antiretroviral therapy (ART) has significantly improved the life expectancy of people living with HIV-1 (PLWH). However, prolonged ART use is linked to metabolic alterations and oxidative stress. The paraoxonase (PON) enzymes, especially PON-1 and PON-2, are critical in maintaining antioxidant balance. Their activity can be influenced by polymorphisms such as Q192R and L55M in PON-1 and A148G and S311C in PON-2. This study examines the impact of these polymorphisms on paraoxonase activity, lipid metabolism, and infection markers in PLWH under various ART regimens. This is a case-control study with 525 participants, 175 healthy controls (HC) and 350 PLWH divided into subgroups: T0 (ART-naïve, n = 48), T1 (ART with reverse transcriptase inhibitors, n = 159), and T2 (ART with protease inhibitors, n = 143). Paraoxonase activity was higher in PLWH (123.0; IQR: 62.0-168.0) compared to HC (91.0; IQR: 48.0-136.0, p < 0.001) but similar between HC and T0 (p = 0.594). T1 (125.0; IQR: 65.5-166.0) and T2 (123.0; IQR: 61.0-182.0) showed higher activity than HC (p = 0.002 and 0.003). Among 61 complete genotypes, 13 were unique to PLWH and 6 to HC (p < 0.001). L55L was more frequent in HC (49.7% vs. 36.9% in PLWH), while M55M was higher in PLWH (p = 0.004). The S311C genotype was more frequent in HC (39.2%) than PLWH (24.9%) (p = 0.003). The L55L genotype conferred 59.9% protection against HIV-1 (OR: 0.401; 95% CI: 0.228-0.704), while the M allele increased susceptibility by ~69% (OR: 1.694; 95% CI: 1.173-2.446). The M55M genotype and/or M allele may be linked to HIV-1 susceptibility. Prolonged ART use elevates PON-1 activity in PLWH.

Mitochondrial diseases are complex disorders caused by nuclear or mitochondrial DNA mutations, leading to oxidative phosphorylation deficiency and excessive production of reactive oxygen species (ROS). While ROS have been well established in the pathogenesis of these diseases, the role of reactive nitrogen species (RNS) remains unclear. In this study, we performed a quantitative analysis of muscle fibers to investigate the relationship between protein nitration and mitochondrial abnormalities (mitochondrial proliferation and cytochrome-c oxidase (COX) deficiency) and factors like genotype, muscle damage, and age. A total of 1961 muscle fibers (303 from 4 controls and 1658 from 29 patients with mitochondrial diseases) were analyzed by immunostaining for nitro-tyrosine. Contrary to previous findings, which identified nitro-tyrosine only in small muscle vessels, we observed a broader distribution affecting the sarcolemma and sarcoplasm. Using multivariate techniques, we identified a significant correlation between protein nitration and mitochondrial proliferation but found no associations with COX deficiency, age, muscle damage, or genotype. These findings suggest that nitrative stress may contribute to mitochondrial dysfunction or play a role in signaling processes that induce mitochondrial biogenesis. Our results provide new insights into the molecular mechanisms of mitochondrial diseases and highlight the potential relevance of protein nitration.

Oxidative stress and inflammation are considered important risk contributors for various diseases. Over the last few decades, increasing attention has been focused on the role of n-3 polyunsaturated fatty acids (n-3 PUFAs) in human health and disease. We aimed to evaluate the effect of n-3 PUFA-enriched chicken meat consumption (~1500 mg of n-3 PUFAs intake per day) for three weeks on oxidative status and antioxidative capacity in young healthy individuals. This was a randomized, double-blinded, controlled trial, in which thirty-nine young healthy people were randomly allocated to eating 500 g/day of regular chicken meat (Control group) or n-3 PUFA-enriched chicken meat (n-3 PUFAs group) over 3 weeks. Subjects' biochemical parameters, including serum lipids level, liver enzymes, serum activities of antioxidant enzymes (glutathione peroxidase (GPx), superoxide dismutase (SOD)), serum oxidative stress markers (thiobarbituric acid reactive substances (TBARS) and ferric-reducing ability (FRAP)), as well as intracellular production of reactive oxygen species (ROS) in peripheral blood mononuclear cells, were assessed before and after completing the three-week dietary protocol. N-3-enriched chicken meat consumption significantly reduced high-sensitivity C reactive protein (hsCRP) serum level and increased the level of the antioxidant defense marker, FRAP. Furthermore, GPx and SOD enzyme activities significantly increased in the n-3 PUFAs group compared to baseline, which was accompanied by significantly decreased ROS production. In healthy young individuals, the 3-week dietary intake of n-3 PUFA-enriched chicken meat significantly increased the serum total antioxidant and anti-inflammatory potential, indicating that n-3 PUFAs may be protective in resting health condition without inflammatory processes.

Rice bran (RB) is a rice processing by-product recognized to be a source of bioactive compounds, including γ-oryzanol and fatty acids, which have interesting bioactivities such as antioxidant and anti-inflammatory effects. This study aims to optimize the supercritical fluid extraction process for recovering these high-value compounds from rice bran with improved bioactivity. A Central Composite Face-Centered Design was employed to optimize the extraction process by varying the temperature (40-80 °C) and pressure (200-500 bar). The optimal extraction conditions were identified at 500 bar and 62 °C that led to the extraction of 17.3% mass yield with 784.5 mg of fatty acids and 36.6 mg of γ-oryzanol per gram of extract, striking a balance between extraction yield and bioactive concentrations. When compared with conventional extractions with n-hexane, supercritical fluid extraction showed similar global yield (18.0 vs. 17.3%) and FA concentration (130.14 vs. 135.70 mg/g of RB) but higher selectivity and extraction yield for γ-oryzanol (18.0 vs. 36.4 mg/g extract; 3.3 vs. 6.3 mg/g of RB). Cellular antioxidant activity assays showed that both extracts reduced the quantity of reactive oxygen species (ROS) up to 50% in Caco-2 cells submitted to oxidative stress. Importantly, supercritical fluid extract was more effective in inhibiting colorectal cancer cell growth (EC50 = 0.9 mg/mL vs. 1.15 mg/mL) than the hexane extract, and this effect was more pronounced than that obtained for pure γ-oryzanol in the same concentration range. These findings highlight the potential of supercritical fluid technology to develop rice bran extracts with antioxidant and antiproliferative properties, underlining the promising applications of this technology in the field of natural product extraction.

Diabetic retinopathy is the most common diabetic complication of the microvasculature and one of the leading causes of acquired vision loss worldwide. Yet, the current treatments for this blinding disease are futile to many diabetics. Accordingly, new biomarkers and therapeutics for diabetic retinopathy are needed. We discovered that STEAP4 (Six-Transmembrane Epithelial Antigen of the Prostate 4) is significantly increased in peripheral blood mononuclear cells of diabetics. STEAP4 expression was gradiently increased from low levels in diabetics without retinopathy to successively higher levels in diabetics with more severe disease. Although the role of STEAP4 in the diabetic retina is unclear, these results provide strong evidence that this metabolic enzyme could be a potential biomarker for diabetic retinopathy progression. Thus, the central goal of this study was to evaluate if this potential biomarker impacts the intrinsic pathologies that lead to the development of diabetic retinopathy. In diabetic mice, STEAP4 was significantly increased and co-localized with 4-Hydroxy-2-nonenal in the Müller glia and photoreceptor layers of the retina. STEAP4 inhibition significantly decreased reactive oxygen species in murine photoreceptor cells, human Müller glia, and retinas of diabetic mice. Administering an intravitreal injection of anti-STEAP4 to diabetic mice halted Occludin degradation in the retinal vasculature. Similarly, anti-STEAP4 treatment of human retina endothelial cells halted cell death mediated by diabetic donor sera. Collectively, our findings provide strong evidence that STEAP4 impacts the intrinsic pathologies that initiate the development of diabetic retinopathy. Suggesting that STEAP4 could be a novel biomarker and clinically relevant therapeutic target for this diabetic complication and blinding disease.