Antioxidant Defense Research Articles

Unconjugated bilirubin promotes uric acid restoration by activating hepatic AMPK pathway

Hyperuricemia and its development to gout have reached epidemic proportions. Systemic hyperuricemia is facilitated by elevated activity of xanthine oxidase (XO), the sole source of uric acid in mammals. Here, we aim to investigate the role of bilirubin in maintaining circulating uric acid homeostasis. We observed serum bilirubin concentrations were inversely correlated with uric acid levels in humans with new-onset hyperuricemia and advanced gout in a clinical cohort consisting of 891 participants. We confirmed that bilirubin biosynthesis impairment recapitulated traits of hyperuricemia symptoms, exemplified by raised circulating uric acid levels and accumulated hepatic XO, and exacerbated mouse hyperuricemia development. Bilirubin administration significantly decreased circulating uric acid levels in hyperuricemia-inducing (HUA) mice receiving potassium oxonate (a uricase inhibitor) or fed with a high fructose diet. Finally, we proved that bilirubin ameliorated mouse hyperuricemia by increasing hepatic autophagy, restoring antioxidant defense and normalizing mitochondrial function in a manner dependent on AMPK pathway. Hepatocyte-specific AMPKα knockdown via adeno-associated virus (AAV) 8-TBG-mediated gene delivery compromised the efficacy of bilirubin in HUA mice. Our study demonstrates the deficiency of bilirubin in hyperuricemia progression, and the protective effects exerted by bilirubin against mouse hyperuricemia development, which may potentiate clinical management of hyperuricemia.

Role of Glutathione in Parkinson's Disease Pathophysiology and Therapeutic Potential of Polyphenols.

Oxidative stress is recognized to have a central role in the initiation and progression of Parkinson's disease (PD). Within the brain, neurons are particularly sensitive to oxidation due in part to their weak intrinsic antioxidant defense. Theoretically, neurons mostly depend on neighboring astrocytes to provide antioxidant protection by supplying cysteine-containing products for glutathione (GSH) synthesis. Astrocytes and neurons possess several amino acid transport systems for GSH and its precursors. Indeed, GSH is the most abundant intrinsic antioxidant in the central nervous system. The GSH depletion and/or alterations in its metabolism in the brain contribute to the pathogenesis of PD. Noteworthy, polyphenols possess potent antioxidant activity and can augment the GSH redox system. Numerous in vitro and in vivo studies have indicated that polyphenols exhibit potent neuroprotective effects in PD. Epidemiological studies have found an association between the consumption of dietary polyphenols and a lower PD risk. In this review, we summarize current knowledge on the biosynthesis and metabolism of GSH in the brain, with an emphasis on their contribution and therapeutic potential in PD. In particular, we focus on polyphenols that can increase brain GSH levels against PD. Furthermore, some current challenges and future perspectives for polyphenol-based therapies are also discussed.

Metallic and metallic oxide nanoparticles toxicity primarily targets the mitochondria of hepatocytes and renal cells.

Nanoparticles (NPs) are utilized in various applications, posing potential risks to human health, tissues, cells, and macromolecules. This study aimed to investigate the ultrastructural alterations in hepatocytes and renal tubular cells induced by metallic and metal oxide NPs. Adult healthy male Wistar albino rats (Rattus norvegicus) were divided into 6 (n = 7) control and 6 treated groups (n = 7). The rats in the treated groups exposed daily to silver NPs, gold NPs, zinc oxide NPs, silicon dioxide NPs, copper oxide NPs, and ferric oxide NPs for 35 days. The members of the control group for each corresponding NPs received the respective vehicle. Liver and kidney tissue blocks from all rats were processed for Transmission Electron Microscopy (TEM) examinations. The hepatocytes and renal tubular cells of all NPs-treated rats demonstrated mitochondrial ultrastructural alterations mainly cristolysis, swelling, membrane disruption, lucent matrices, matrices lysis, and electron-dense deposits. However, other organelles demonstrated injury but to a lesser extent in the form of shrunken nuclei, nuclear membrane indentation, endoplasmic reticulum fragmentation, cellular membranes enfolding, brush border microvilli disruption, lysosomal hyperplasia, ribosomes dropping, and peroxisome formation. One may conclude from the findings that the hepatocytes and the renal tubular cells mitochondria are the main targets for nanoparticles toxicity ending in mitochondrial disruption and cell injury. Further studies taking into account the relation of mitochondrial ultrastructural damage with a weakened antioxidant defense system induced by chronic exposure to nanomaterials are needed.

Coupling of biochar and silicon for Phyto-management of Cd contaminated soil using Brachiariamutica

Contamination of soil with heavy metals is a threatening global environmental problem. With increasing urbanization, it is very important to design economical and environment-friendly mitigation measures to have pollutant free soil. Phytoremediation is an advancing technique to extract pollutants from soil to achieve eco-sustainability. This study aimed to investigate the combined impact of biochar and silicon on growth attributes of Brachiaria mutica grown in cadmium (Cd) contaminated soil. The biochar was prepared by co-pyrolysis of agricultural left-over biomass (rice husk, bamboo leaves and corn cob in a 1:1:1 ratio) and physio-chemical characters were studied by FTIR, SEM-EDX and proximate analysis. A pot study was conducted to evaluate the potency of biochar and silicon in lowering the Cd uptake by para grass grown under Cd spiked soil. Total 8 treatments were planned by taking 1 % and 2 % biochar with 0.01 % and 0.02 % silicon. The results have shown that treatment 8 (2 % biochar and 0.02 % silicon) exhibited maximum improvement in growth parameters such as shoot length by 2.64-fold and root length by 44.9 %, along with improving the antioxidant defense system of Para grass (CAT by 2-fold and POD by 56.4 %). Application of treatment 8 also decreased Cd concentration in the shoot and root by 48.8 % and 47.4 %, respectively. Treatment 8 was most effective in reducing CaCl2 extractable Cd in soil up to 56.1 %. Based on this data, treatment 8 was most effectual in suppressing Cd stress. Biochar produced from other agricultural waste material along with Si as inorganic amendment can be used to immobilize other toxic heavy metals at field level. Heavy metals immobilization potential of Si and biochar can be tested by harvesting other grasses and oil seed crop species.

Understanding the Significance of Raffinose Family Oligosaccharides in Seed Physiology

Seed vigour and longevity are pivotal agronomic traits with profound implications for crop yield, food security, and the global economy. Seed longevity, often defined by the duration of seed viability, is crucial for effective gene bank management, influencing seed regeneration cycles and ensuring the long-term conservation of plant genetic resources. The inevitable process of seed deterioration, driven by a complex network of biochemical reactions, leads to altered metabolism and damage to critical cellular components such as membranes, DNA, mitochondria, proteins, and the antioxidative defence system. In recent research, Raffinose family oligosaccharides (RFOs) have emerged as key contributors to enhancing seed vigour and longevity. These sugars perform multiple functions in plants, including tolerance to abiotic and biotic stresses, regulation of seed germination, and maintenance of desiccation tolerance, all of which are essential for overall seed health. Studies suggest that RFOs significantly bolster seed vigour and longevity through mechanisms such as cytoplasmic vitrification, water replacement, and osmoprotection in dried seeds. These oligosaccharides are particularly abundant in the seeds of leguminous crops and are also found in roots and specialized storage organs. The glassy state formed by RFOs is vital for protecting cells from oxidative damage caused by reactive oxygen species (ROS), enhancing the stability of enzymes, and preventing deleterious conformational changes in proteins. Furthermore, delaying the degradation of RFOs has been shown to inhibit premature germination, underscoring their critical role in early seedling development and successful crop establishment.

Antioxidant defence mechanism in hen egg: An immunity Booster

Dietary antioxidants are considered to be a vital agent that has the potential to reduce the risk of dangerous diseases by stabilizing redox homeostasis. Hen eggs are the most intrinsic part of our breakfast and a bang-up source of high-quality proteins, lipids, minerals and vitamins. Eggs show an antioxidant property due to the presence of proteins in both the yolk and white i.e. ovalbumin, Ovotransferrin and phosvitin. It’s also a fact that antioxidants in the eggs can be enhanced artificially by manipulating the poultry feed given to the hens. Lack of antioxidants and nutrients leads to a number of diseases including cancer, cardiovascular diseases and age-related macular degeneration.

Biomarkers of Oxidative Stress in Diabetic Microvascular Complications Review Article

Reactive oxygen species (ROS) are produced as a result of biochemical processes that are not in balance with the body's antioxidant defense mechanism. This metabolic dysfunction is referred to the oxidative stress (OS). Metabolic dysfunction-associated diseases are affected by changes in the redox balance. It is now widely recognized that oxidative stress significantly affects diabetes mellitus (DM), particularly type 2 diabetes. The biochemical changes associated with DM could disturb the oxidative milieu, leading to several microvascular complications in diabetic patients. Thus, DM is a perfect disease to explore the harmful consequences of oxidative stress and how to treat it. Oxidative stress triggered by hyperglycemia is an important contributor to the effects of diabetic microvascular diseases. Uncontrolled hyperglycemia carried by deficiencies in insulin secretion or action produces a number of problems, such as peripheral vascular disorders, nephropathy, neuropathy, retinopathy, increased morbidity and/or mortality, as well as the incidence of diabetes mellitus (DM) are rising globally. The development and progression of diabetic problems are strongly correlated with reactive oxygen species and oxidative stress, according to a wide body of research. This review aims to explore various markers of oxidative stress and the role of ROS in the pathogenesis and progression of late diabetic microvascular complications.

Assessing the response lettuce and arugula to MC-LR-contaminated water irrigation: photosynthetic changes and antioxidant defense.

Irrigation of crops with cyanotoxin-contaminated water poses a significant risk to human health. The direct phytotoxic effects of microcystin-LR (MC-LR), one of the most toxic and prevalent microcystin variants in water bodies, can induce physiological stress and hinder crop development and production. This study investigated the impact of environmentally relevant concentrations of MC-LR (1 to 10µg L-1) on photosynthetic parameters and antioxidant response of lettuce (Lactuca sativa L.) and arugula (Eruca sativa L.) following irrigation with contaminated water. During the 15-day experiment, lettuce and arugula were exposed to various concentrations of MC-LR, and their photosynthetic rates, stomatal conductance, leaf tissue transpiration, and intercellular CO2 concentrations were measured using an infrared gas analyzer. These results suggest that the influence of MC-LR on gas exchange in crops is concentration-dependent, with notable disruptions during exposure and recovery tendency during detoxification. Antioxidant response analysis revealed that glutathione S-transferase (GST) and superoxide dismutase (SOD) activities were upregulated during the exposure phase in the presence of MC-LR. However, GST activity decreased during the detoxification phase in both crops, although the effects of the toxin at 10µg L-1 were still evident in arugula. The internal H2O2 concentration in the crops increased after exposure to MC-LR, showing a time- and concentration-dependent pattern, with an increase during the exposure phase (days 1-7) and a decrease during the detoxification phase (days 8-15). Irrigation of lettuce and arugula with MC-LR-contaminated water affected various aspects of the photosynthetic apparatus and antioxidant responses, which could influence the general health and productivity of exposed crops at environmentally relevant microcystin concentrations. Furthermore, investigation of additional vegetable species and long-term MC-LR exposure can be crucial for understanding the extent of contamination risk, detoxification mechanisms, and other parameters affecting these crops.

Abstract B004: Targeting Metabolic Vulnerabilities in Pancreatic Cancer: The Synergistic Anti- Tumor Effects of a Ketogenic Diet and IDH1 Inhibition

Abstract Background: A ketogenic diet, characterized by high fat (90% kCal) and low carbohydrates (5% kCal), induces ketosis. Previous research suggests that a ketogenic diet shifts cancer cell metabolism from glycolysis to the tricarboxylic acid (TCA) cycle in the mitochondria. While the overall impact on cancer growth remains uncertain, most studies suggest an anti-cancer effect. We hypothesize that understanding the molecular and biochemical adaptations of pancreatic cancer cells to a ketogenic diet will reveal metabolic vulnerabilities and lead to rational therapeutic strategies that complement the diet. Methods: Mice were fed a ketogenic diet, with control mice on a normal diet. Pancreatic cancer xenografts were monitored for growth and subjected to biochemical analyses. Tumor metabolites were measured using LC/GC-MS, and oxidative stress was assessed by NADP+/NADPH, NAD+/NADH levels, and lipid peroxidation assays. Enzyme expression was determined by Western blot. In vitro, mitochondrial function was analyzed using the Seahorse FX Analyzer, and cell growth was measured by PicoGreen DNA quantitation. Results: A ketogenic diet slowed pancreatic cancer growth in multiple in vivo models, including MIA-PaCa2, KPC, and patient-derived xenografts. TCA metabolites increased in xenografts exposed to the ketogenic diet, with a significant upregulation of TCA cycle-associated enzymes. Specifically, the expression of BDH1 (a ketolytic enzyme), IDH1 (supports antioxidant defense and mitochondrial function), and IDH2 (mitochondrial homolog of IDH1) were elevated. Conversely, the glycolytic enzyme G3P was reduced. Additionally, a ketogenic diet induced oxidative stress in pancreatic cancer in vivo. Combining a ketogenic diet with an IDH1 inhibitor impaired antioxidant defense and mitochondrial function, resulting in significantly reduced tumor proliferation compared to either treatment alone. In vitro studies indicated that low glucose and fatty acids primarily drive the reduced proliferation of pancreatic cancer cells on a ketogenic diet, while exogenous ketone bodies are utilized for energy under glucose deprivation, generally promoting tumor growth. Conclusion: A ketogenic diet exerts a strong anti-tumor effect in multiple pancreatic cancer mouse models, likely due to low glucose and increased fatty acid load. The metabolic shift towards an oxidative phosphorylation (OXPHOS) phenotype makes pancreatic cancer cells particularly vulnerable to antioxidant and mitochondrial inhibitors. Citation Format: Omid Hajihassani, Mehrdad Zarei, Soubhi Tahan, Peter Gallagher, William Beegan, John Speers, James Choi, Aya Murray, Alexander Loftus, Helen Cheng, Anusha Mudigonda, Karen Ji, Jonathan Hue, Hallie Graor, Jordan Winter. Targeting Metabolic Vulnerabilities in Pancreatic Cancer: The Synergistic Anti- Tumor Effects of a Ketogenic Diet and IDH1 Inhibition [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B004.

The Effect of Glutathione on Development and Prognosis in Non-Muscle-Invasive Bladder Cancer.

Background: Glutathione, along with its related enzymes, constitutes a key antioxidant defense mechanism against oxidative stress and cancer formation in the body. Among urological malignancies, bladder cancer ranks second following prostate cancer. Oxidative stress has significant involvement in the development and prognosis of bladder cancer. This investigation aimed to examine the impact of glutathione on prognosis in patients with non-muscle-invasive bladder cancer. Methods: This study included 98 patients with high grade non-muscle-invasive bladder cancer who had undergone intravesical Bacillus Calmette-Guérin therapy and 30 healthy controls with no history of uroepithelial carcinoma of the bladder. The patients with bladder cancer were evaluated in three subgroups. Group 1 consisted of 41 patients who did not experience recurrence during follow-up, Group 2 included 28 patients who had recurrent tumors, and Group 3 consisted of 29 patients who progressed to muscle-invasive stages. Blood samples were collected from all participants. Blood levels of reduced, oxidized, and total glutathione were measured spectrophotometrically. Results: Reduced glutathione levels significantly differed among the groups (p < 0.001), attributed to the control group exhibiting higher reduced glutathione levels compared with Groups 1, 2, and 3 (p < 0.001). There were no significant differences in reduced glutathione levels between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 (p > 0.05). Total glutathione levels varied significantly among the groups (p < 0.001), with the control group having higher levels than Groups 1, 2, and 3 (p < 0.001). No significant differences were detected between any of the paired patient groups in terms of total glutathione levels (p > 0.05). Regarding oxidized glutathione levels, the difference was statistically significant (p < 0.001), with the control group showing lower levels than the remaining three groups (p < 0.001). Paired comparisons revealed no significant differences in oxidized glutathione levels (p > 0.05). Conclusions: This study revealed that glutathione had an effect on the emergence of bladder cancer but did not affect its prognosis. Nevertheless, we recommend that future studies with larger bladder cancer patient cohorts should be conducted to comprehensively determine the impact of glutathione on the prognosis of this cancer.

Mitigating chromium stress in tomato plants using green-silicone nanoparticles: Enhancing cellular oxidative stress management and chromium reduction

Nano-enabled approach has become the promising option for resolving heavy metal (HMs) contamination and improving the crop production. Here, current study explored mechanism involved in how green silicon nanoparticles (SiNPs) alleviating the chromium (Cr) induced toxicity in tomato. Green SiNPs in spherical shape with size 8–40 nm were synthesized with artemisia annua leaves extract and characterization performed by modern characterization method. The results of the green house experiment demonstrated that SiNPs at dose of 150 mg kg−1 surprisingly improved the biomass and root architecture of tomato plants. SiNPs supplementation also positively enhanced the photosynthesis pigments and leaf gas exchange attributes of Cr-stressed plants. Besides this, SiNPs150 mg kg−1 elevated antioxidant enzymes activities which scavenging ROS and reduced Cr-caused oxidative destruction. Furthermore, qPCR assay showed upregulation of the antioxidant defense related genes with the application of SiNPs under Cr stress. Transmission Electron Microscopy analysis showed that SiNPs application effectively alleviated Cr-induced damage to leaf ultrastructure and had a substantial impact on Cr and Si accumulation in plants. In conclusion, the utilization of green SiNPs as nano-fertilizers exhibits great potential as a strategy for agriculture to alleviate the adverse effects of HMs stress, safeguard food safety, and sustainable agriculture in the future.

Effects of diphenhydramine on crayfish cytochrome P450 activity and antioxidant defence mechanisms: First evidence of CYP2C- and CYP3A-like activity in marbled crayfish

Growing evidence has reported that diphenhydramine (DPH), an ionisable antihistamine, is widely present in surface waters across the world. Relative to vertebrates studied, its impact on invertebrates, particularly concerning cytochrome P450 (CYP) metabolism and oxidative stress, remains poorly understood. In this study, we aimed to investigate the effects of 2, 20, and 200 µg/L DPH on marbled crayfish (Procambarus virginalis) after 96-h exposure. Specifically, we assessed CYP activity, antioxidant enzyme responses, and acetylcholinesterase (AChE) activity in gills, muscle, and hepatopancreas. The crayfish CYP metabolised fluorogenic CYP-metabolic substrates of 7-benzyloxy-4-trifluoromethylcoumarin (BFC) and dibenzylfluorescein (DBF), which evidenced the activity of CYP2C and CYP3A isoforms, well known in mammalian detoxification metabolism. Both BFC and DBF dealkylations showed a positive correlation with each other but were negatively correlated to water and haemolymph DPH concentrations. Exposure to 200 µg/L DPH elicited an apparent inhibition trend, albeit not significant, in BFC- and DBF-transformation activities in crayfish. Other tested 7-benzyloxyresorufin and 7-pentoxyresorufin substrates were poorly metabolised, suggesting their relatively low activity or the lack of mammalian-like CYP1A and CYP2B isoforms in marbled crayfish. The significant modulation of antioxidant enzymes was demonstrated in gills and hepatopancreas. The exposure to DPH did not alter the activity of AChE. Integrated biomarker response version 2 showed the highest cumulative effect of DPH exposure on gills, implying that gill tissue is the most reliable matrix for evaluating DPH toxicity. Activities of glutathione peroxidase and glutathione-S-transferase were the most deviated determinants among the investigated biomarkers, providing insights into the DPH toxicity in crayfish. This study brought the first insight into utilising the fluorogenically active substrates BFC and DBF to demonstrate the CYP involvement in the detoxification metabolism in marbled crayfish. Further, our results provided information on valuable antioxidant defence mechanisms and biomarker responses for a future DPH toxicity assessment in aquatic organisms.

Dose rate dependent genotoxic and metabolic effects predict onset of impaired development and mortality in Atlantic salmon (S. salar) embryos exposed to chronic gamma radiation

Release of radionuclides to the environment from either nuclear weapon and fuel cycles or from naturally occurring radionuclides (NORM) may cause long term contamination of aquatic ecosystems and chronic exposure of living organisms to ionizing radiation, which in turn could lead to adverse effects compromising the sustainability of populations. To address the effects of chronic ionizing radiation on the development of fish, Atlantic salmon embryos were exposed from fertilization until hatching (88 days, 550 day-degree) to dose rates from 1 to 30 mGy·h−1 gamma radiation (60Co). The lowest adopted dose rate was similar to the highest doses measured in some water bodies right after the Chernobyl accident (1 mGy·h−1), however, well above current environmentally realistic scenarios (20 μGy·h−1), or the threshold assumed for significant effects on fish population (40 μGy·h−1). Dose dependent effects were observed on survival, hatching, morbidity, DNA damage, antioxidant defenses, and metabolic status. Histopathological analysis showed dose rate dependent impairment of eye and brain tissues development and establishment of epidermal mucus cell layers accompanied by increased DNA damage at doses ≥1.3 Gy (dose rates ≥1 mGy·h−1).At ≥32.8 Gy (dose rates ≥20 mGy·h−1) deformities and developmental growth defects resulted in respective 46 and 95 % pre-hatch mortality. The 10 mGy·h−1 exposure (≥ 12 Gy total dose) caused significantly increased DNA damage, impaired eye development, and both premature and delayed hatching, while no deformities or effect on survival were observed. We observed a dose rate dependent reduction from dose rate ≥ 20 mGy·h−1 (≥ 27 Gy total dose) on antioxidant SOD, catalase and glutathione reductase enzyme activities. The reduction of antioxidant enzyme activities was in line with observed developmental delay and disturbance to time of hatching. Metabolomic profiles showed a clear shift at dose rates ≥10 mGy·h−1 (≥ 12 Gy total dose) in pathways related to oxidative stress, detoxification, DNA damage and repair. Due to gamma radiation exposure, a switch of central metabolism from glycolysis, citric acid cycle and lactate production towards pentose phosphate pathway indicated a rewiring mechanism for increased production of reductive equivalents to maintain redox homeostasis at the expense of energy output and thus embryonic development.

Oxygen, the Paradox of Life and the Eye

Oxidative stress, caused by the formation of free radicals, such as reactive oxygen species (ROS), leads to cell and tissue degradation, contributing to various diseases and aging. While oxygen is essential for aerobic organisms, it inevitably causes oxidative stress. Antioxidants protect against damage from free radicals, and oxidative stress arises when an imbalance occurs between free radical production and antioxidant defenses. However, when investigating whether an excess of antioxidants, almost eliminating oxidative stress, could benefit aging and disease susceptibility, it was observed that a basic level of oxidative stress appears necessary to maintain the correct homeostasis of tissues and organs and life in general. Therefore, this review aimed to compile the most significant and recent papers characterizing and describing the dual role of oxygen as a molecule essential for life and as a precursor of oxidative stress, which can be detrimental to life. We conducted targeted searches in PubMed and Google browsers to gather all relevant papers. We then focused on the eye, an organ particularly vulnerable due to its high metabolic activity combined with direct exposure to light and environmental pollutants, which produces a substantial number of free radicals (mainly ROS). We present a curated selection of relevant literature describing the main ocular pathologies of the posterior and anterior segments of the eye, highlighting oxidative stress as a significant contributing factor. Additionally, we report how endogenous and exogenous antioxidants can mitigate the development and progression of these diseases. Finally, we consider a frequently overlooked aspect: the balance between oxidants and antioxidants in maintaining the homeostatic equilibrium of tissues and organs. It is widely recognized that when oxidants overwhelm antioxidants, oxidative stress occurs, leading to negative consequences for the organism's homeostasis. However, we emphasize that a similarly dangerous situation can arise when the presence of antioxidants overwhelms the production of free radicals, drastically reducing their amount and adversely affecting aging and longevity. Unfortunately, no specific studies have addressed this particular situation in the eye.

Interface potential-induced natural antioxidant mimic system for the treatment of Alzheimer’s disease

Although the pathogenesis of Alzheimer’s disease (AD) is still unknown, the molecular pathological phenomena is clear, mainly due to mitochondrial dysfunction and central nervous system inflammation caused by imbalanced antioxidant capacity and synaptic dysfunction, so antioxidant therapy is still the preferred treatment for AD. However, although antioxidant enzymes have high catalytic efficiency, the substrate spectrum is narrow; Antioxidants have wider range of effects, but their efficiency is low. Since the antioxidant defense system in high-grade organisms is composed of both enzymatic and non-enzymatic systems, therefore we synthesized a metal-organic framework (MOF) with superoxide dismutase activity, and depending on the interface potential effect, curcumin was loaded to construct a synergistic antioxidant treatment system. More importantly, due to the complementary surface electrostatic potential between MOF and curcumin, the system exhibited both good antioxidant activity and efficient β-amyloid plaque scavenging ability, which slowed down the cognitive dysfunction in the brain of AD mice.

Bixin Combined with Metformin Ameliorates Insulin Resistance and Antioxidant Defenses in Obese Mice.

Bixin (C25H30O4; 394.51 g/mol) is the main apocarotenoid found in annatto seeds. It has a 25-carbon open chain structure with a methyl ester group and carboxylic acid. Bixin increases the expression of antioxidant enzymes, which may be interesting for counteracting oxidative stress. This study investigated whether bixin-rich annatto extract combined with metformin was able to improve the disturbances observed in high-fat diet (HFD)-induced obesity in mice, with an emphasis on markers of oxidative damage and antioxidant defenses. HFD-fed mice were treated for 8 weeks with metformin (50 mg/kg) plus bixin-rich annatto extract (5.5 and 11 mg/kg). This study assessed glucose tolerance, insulin sensitivity, lipid profile and paraoxonase 1 (PON-1) activity in plasma, fluorescent AGEs (advanced glycation end products), TBARSs (thiobarbituric acid-reactive substances), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the liver and kidneys. Treatment with bixin plus metformin decreased body weight gain, improved insulin sensitivity, and decreased AGEs and TBARSs in the plasma, liver, and kidneys. Bixin plus metformin increased the activities of PON-1, SOD, CAT, and GSH-Px. Bixin combined with metformin improved the endogenous antioxidant defenses in the obese mice, showing that this combined therapy may have the potential to contrast the metabolic complications resulting from oxidative stress.

Acute and prolonged effects of Bacillus amyloliquefaciens GF424-derived SOD on antioxidant defense in healthy individuals challenged with intense aerobic exercise

Reactive oxygen species (ROS) play a vital role in cellular functions but can lead to oxidative stress and contribute to degenerative diseases when produced in excess. Maintaining redox balance is essential and can be achieved through innate defense mechanisms or external antioxidants. Superoxide dismutase (SOD) is a key enzyme that mitigates intracellular oxidative stress by converting harmful free radicals into hydrogen peroxide, which is subsequently neutralized by catalase and glutathione peroxidase. Previous studies have demonstrated the antioxidant capabilities of SOD derived from Bacillus amyloquefaciens GF424 (BA-SOD) in murine models exposed to either irradiation or SOD1 gene deletion. In this study, a randomized clinical trial was conducted to evaluate the antioxidative benefits of BA-SOD in healthy individuals undergoing acute aerobic exercise (AAE). Eighty participants were randomly assigned to receive either BA-SOD or a placebo for 8 weeks. Antioxidant enzyme activities and glutathione levels were measured before, immediately after, and 30 min post-exercise. A single dose of BA-SOD significantly reduced ROS levels induced by AAE, primarily by enhancing SOD activity in erythrocytes and activating glutathione peroxidase. Continuous BA-SOD administration was associated with a sustained increase in catalase activity and elevated levels of reduced glutathione (GSH). Transcriptomic and metabolomic analyses revealed that a single BA-SOD dose facilitated GSH oxidation, as evidenced by decreased levels of serine, glutamine, and glycine, and increased pyroglutamate levels. Additionally, repeated dosing led to increased expression of genes encoding isocitrate dehydrogenase and malic enzyme, which are involved in NADPH synthesis, as well as nicotinamide phosphoribosyl transferase and NAD kinase, which are essential for NADP availability–critical for converting oxidized glutathione (GSSG) back to GSH. These molecular insights align with clinical observations, suggesting that both acute and long-term BA-SOD supplementation may effectively enhance antioxidant defenses and maintain redox balance under oxidative stress conditions.

Interplay of UV-filter pollution and temperature rise scenarios on Mytilus galloprovincialis health: Unveiling sperm quality and adult physiology, biochemistry, and histology insights

Addressing the impacts of emerging contaminants within the context of climate change is crucial for understanding ecosystem health decline. Among these, the organic UV-filters 4-methylbenzylidenecamphor (4-MBC) and benzophenone-3 (BP-3) are widely used in cosmetics and personal care products. Their unique physico-chemical properties, along with their growing commercialization and consumption, have made them ubiquitous in aquatic environments through both direct and indirect releases, raising significant concerns about their potential threats to inhabiting biota. Additionally, increasing surface water temperatures exacerbate ecological risks, making it imperative to understand the implications for non-target species at different biological levels. This study investigated the short- and long-term effects of UV-filters 4-MBC or BP-3, at ecologically relevant concentrations, combined with current and predicted warming scenarios, on the performance and male reproductive health of Mytilus galloprovincialis mussel populations. Using biomarkers across sub-cellular, cellular, tissue, and individual levels, the study revealed significant physiological and biochemical impairments in both sperm cells and adults exposed to UV-filters. Temperature emerged as the primary driver influencing mussel responses and modulating the impacts of 4-MBC/BP-3, emphasizing their sensitivity to temperatures outside the optimal range and interactive effects between stressors. Specifically, sperm motility declined with increasing UV-filter concentrations, while temperature alone influenced ROS production, leading to compromised mitochondrial activity and DNA damage in the presence of combined stressors, indicative of potential reproductive impairments. Adults exhibited high UV-filter bioconcentration potential in whole tissues, compromised physiological status, morphophysiological changes in digestive glands, oxidative stress, and alterations in metabolic capacity, antioxidant defences, and biotransformation mechanisms, correlating with UV-filter exposure and temperature increase. Among the UV-filters tested, 4-MBC was the most detrimental, especially when combined with warming. Overall, this study underscores the vulnerability of M. galloprovincialis to cumulative stressors and highlights the importance of employing a multi-biomarker approach to assess and mitigate the impacts of stressors on coastal ecosystems.

Biochar improves morpho-physiological growth, osmolyte accumulation, nutrients balance, anti-oxidative defense and oil productivity of Brassica under flooding stress

Soil flooding is a serious abiotic stress that can repress plant growth and yield. The intensity of flooding stress is continuously increasing owing to rapid climate change and changes in rain intensity and frequency. Biochar (BC) emerges as an important soil amendment to mitigate adverse impacts of abiotic stress. The role of BC against different stresses is well reported, however, its role under flooding stress is not determined yet. Thus, this experiment was conducted to determine the role of BC on the performance of brassica crops under flooding stress. The experiment was comprised of well-watered (WW) and flooding stress (FS) conditions and biochar application: control, 1% biochar, and 2.5% biochar. The results indicated that flooding stress stunted the plant growth and impaired the photosynthetic pigments, leaf water status, osmolytes yield and yield traits, and oil concentration and increased the electrolyte leakage (EL), hydrogen peroxide (H2O2) and malondialdehyde (MDA) concentration. The application of BC at the rate of 2.5% mitigated the adverse impacts of salinity and upgraded the antioxidant activities (~50-120%), reduced the oxidative stress markets (~70-300%), and increased the leaf water status, photosynthetic pigments, osmolyte accumulation, nutrient uptake, yield traits, and oil contents. In conclusion, BC application can improve the productivity and oil yield of brassica under drought stress by improving plant physiological and biochemical functioning. However, more in depth studies are direly needed to explore the mechanism of BC to induce flood tolerance.

Gamma-aminobutyric acid as a regulator of astaxanthin production in Haematococcus lacustris under salinity: Exploring physiology, signaling, autophagy, and multi-omics landscape

Haematococcus lacustris-derived natural astaxanthin has significant commercial value, but stressful conditions alone impair cell growth and reduce the total productivity of astaxanthin in industrial settings. This study used gamma-aminobutyric acid (GABA) to increase biomass, astaxanthin productivity, and tolerance to salinity. GABA under NaCl stress enhanced the biomass to 1.76 g/L, astaxanthin content to 30.37 mg g−1, and productivity to 4.10 mg/L d−1, outperforming the control. Further analysis showed GABA enhanced nitrogen assimilation, Ca2+ level, and cellular GABA content, boosting substrate synthesis, energy metabolism, osmoregulation, autophagy, and antioxidant defenses. GABA also activated signaling pathways involving phytohormones, cAMP, cGMP, and MAPK, aiding astaxanthin synthesis. The application of biomarkers (ethylene, salicylic acid, trans-zeatin) and an autophagy inhibitor cooperated with GABA to further enhance the total astaxanthin productivity under NaCl stress. Combining GABA with 25 μM salicylic acid maximized astaxanthin yield at 4.79 mg/L d−1, offering new strategies for industrial astaxanthin production.