Prevent Lipid Peroxidation Research Articles

Abstract IA10: Immune side effects in ferroptosis-targeted therapy

Abstract Ferroptosis, a regulated form of cell death driven by lipid peroxidation, has emerged as a promising strategy in cancer therapy, complementing established modalities such as chemotherapy, immunotherapy, and radiotherapy. While the mechanisms of ferroptosis are highly context-dependent, the classical approach to inducing ferroptosis involves targeting the GPX4 (glutathione peroxidase 4) pathway. GPX4 is a critical enzyme that detoxifies lipid hydroperoxides (L-OOH) by reducing them to non-toxic lipid alcohols (L-OH) using glutathione (GSH) as a cofactor, thereby preventing lipid peroxidation and ferroptotic cell death. Although targeting GPX4 effectively induces ferroptosis in cancer cells, its widespread expression in both tumor and normal cells presents challenges. Direct inhibition of GPX4 can lead to unintended immune cell death, potentially impairing antitumor immunity by reducing the activity of cytotoxic T cells and other immune effectors essential for robust immune responses. This immunosuppressive effect could undermine the therapeutic benefits of ferroptosis-targeted therapies. To overcome this limitation, alternative strategies have been explored. For instance, non-direct targeting of GPX4, such as inducing TRIM25-mediated degradation of GPX4, has shown promise in selectively killing cancer cells while sparing normal tissues and preserving immune function. This approach minimizes toxicity and maintains the activity of key immune cells, including cytotoxic T cells, enhancing the overall efficacy of ferroptosis-based treatments. Understanding the potential risks and immune-related side effects of ferroptosis-targeted therapies is critical for their successful clinical translation. Citation Format: Daolin Tang. Immune side effects in ferroptosis-targeted therapy. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA10

Metallofullerenol Gd@C82(OH)22 preserves human erythrocyte plasma membrane integrity from AAPH-induced oxidative stress: molecular mechanisms and antioxidant activity.

Metallofullerenols and fullerenols have attracted attention due to their remarkable ability to interact with various biologically relevant molecules, paving the way for biomedical applications, ranging from medical imaging techniques to drug carriers, acting with increased efficiency and reduced side effects. In this work, we investigated the effects of two fullerene derivatives, Gd@C82(OH)22 and C70(OH)12, on erythrocyte membrane components under oxidative stress conditions induced by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) as a source of peroxyl radicals. The results demonstrated that gadolinium encapsulation within the fullerene cage enhanced the electron affinity of Gd@C82(OH)22, resulting in stronger antioxidant activity. Gd@C82(OH)22 formed a protective hydrophilic layer at the lipid-water interface, effectively preventing lipid peroxidation, oxidative protein damage, and potassium leakage, outperforming C70(OH)12. Both compounds improved membrane fluidity, but Gd@C82(OH)22 exhibited superior preservation of the erythrocyte lipid bilayer and protein function. Additionally, Gd@C82(OH)22 maintained the anion exchange function of Band 3 protein, which is critical for ionic homeostasis, by preventing oxidation-induced aggregation and preserving thiol groups. Despite its limited membrane penetration, Gd@C82(OH)22 stabilized membrane components through hydrogen bonding, which indirectly enhanced membrane stiffness and fluidity under oxidative stress. This external protection of membrane integrity reduced the risk of lipid peroxidation and oxidative damage to erythrocyte proteins. In contrast, C70(OH)12, while effective in protecting membrane lipids, was less effective in preserving protein structure. These findings highlight the unique protective properties of Gd@C82(OH)22, attributed to polarization effects induced by the encapsulated Gd atom. This study indicates that metallofullerenols, such as Gd@C82(OH)22, may have therapeutic potential in mitigating oxidative damage.

In Vitro and In Ovo Evaluation of Oenothera biennis L. Oil as an Alternative Preservative for Oil-Based Products.

There is a growing need for safer alternatives to synthetic additives commonly used in lipophilic carriers for products such as foods, pharmaceuticals, personal care items, and cosmetics. Natural antioxidants, which prevent lipid peroxidation while providing additional health benefits, offer a promising solution. Evening primrose oil, a rich source of antioxidant compounds with numerous biological benefits, emerges as a potential natural preservative for oil-based products. Our study evaluates a combination of sunflower oil, a widely used cold-pressed oil, with evening primrose oil for potential applications in various fields such as cosmetic, pharmaceutical, or food manufacturing. Various methods were applied to assess oxidative stability by calculating the peroxide value, the p-anisidine value, and the total oxidation value, while biological safety was evaluated using the chick embryo's chorioallantoic membrane and histological analysis. The findings highlight that evening primrose oil, with its balanced effects on epithelial tissues and vascularization, as well as its strong anti-lipid peroxidation properties, is a suitable alternative to synthetic preservatives when used in combination with cold-pressed oils. This proposed oil combination, emphasizing the safety and beneficial properties of evening primrose oil, shows significant potential for applications in the pharmaceutical industry, dermatology, cosmetology, and food manufacturing.

Fruit Extracts Incorporated into Meat Products as Natural Antioxidants, Preservatives, and Colorants

Nowadays, natural antioxidants, especially those found in fruits, are preferred over synthetic ones when used in a variety of meat products. Natural alternatives are preferred by consumers because synthetic additives in meat products have been connected to allergic reactions and other health-related problems. Fruits are abundant in phenolic compounds, providing them with particularly powerful antioxidants. Lipid oxidation is inhibited, allowing meat products to have an extended shelf life when enriched with fruit-derived components. The present study explores the potential of bioactive compounds derived from fruits, specifically phenolics, to improve the quality of meat products by virtue of their antimicrobial, antioxidant, and color-stabilizing qualities. In this review, the effects of 18 fruits on oxidative stability, antimicrobial activity, and color enhancement in meat products were investigated. The first section of this paper focuses on a presentation of the phytochemical composition and overall biological characteristics of the fruits. The thiobarbituric acid test, the peroxide value, and oxidative protein changes were used to assess oxidative stability. By scavenging free radicals or chelating metals, the phenolic compounds not only prevent lipid peroxidation but also protect myoglobin from oxidation, thereby improving the color of meat substitutes. Phenolic compounds provide antimicrobial actions by compromising bacterial cell walls, disrupting membrane integrity, or inhibiting essential enzymes necessary for microbial growth. Fruit extracts have shown effectiveness against foodborne pathogens and spoiling bacteria. Adding fruits to meat products is a promising way to improve their nutritional profile, sustainability, and quality. In order to guarantee consumer safety, future studies must concentrate on thorough toxicological analyses of fruit extracts meant to be used in food.

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

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

Ayahuasca Pretreatment Prevents Sepsis-Induced Anxiety-Like Behavior, Neuroinflammation, and Oxidative Stress, and Increases Brain-Derived Neurotrophic Factor.

The psychoactive decoction Ayahuasca (AYA) used for therapeutic and religious purposes by indigenous groups and peoples from Amazonian regions produces anti-inflammatory and neuroprotective effects. Thus, it may be useful to attenuate the neuroinflammation and related anxiety- and depressive-like symptoms elicited by inflammatory insults such as sepsis. Rats were pretreated for 3days with different doses of AYA. Twenty-four hours after, cecal ligation and puncture (CLP) was performed. On days 1-4, post-CLP behavioral tests to assess anxiety-like behavior were performed. After 24-h, neuroinflammation, oxidative stress, myeloperoxidase activity, and mitochondrial metabolism were assessed in the prefrontal cortex (PFC), hippocampus (HP), and cortex. AYA pretreatment increased the time spent in the open arms of the elevated plus maze and prevented the sepsis-induced hyper-grooming and -rearing behavior, suggesting an anxiolytic effect. AYA pretreatment increased the levels of the anti-inflammatory interleukin 4, in the PFC and the cortex, and brain-derived neurotrophic factor in the cortex. Moreover, AYA pretreatment increased myeloperoxidase activity in the PFC and the HP and decreased nitrite/nitrate concentration in the PFC, HP, and cortex of septic rats, suggesting enhanced neutrophil activation and decreased nitric oxide signaling. Furthermore, AYA pretreatment prevented lipid peroxidation in the PFC, HP, and cortex of septic rats as measured by decreased levels of thiobarbituric acid reactive substances. Levels of protein carbonyls and activity of superoxide dismutase, citrate synthase, succinate dehydrogenase, and mitochondrial respiratory chain were not affected. Together,AYA represents a promising approach to prevent sepsis-induced neuroinflammatory and oxidative stress and associated anxiety-like symptoms.

Deficiency in glutathione peroxidase 4 (GPX4) results in abnormal lens development and newborn cataract

The human lens is composed of a monolayer of lens epithelial cells (LECs) and elongated fibers that align tightly but are separated by the plasma membrane. The integrity of the lens plasma membrane is crucial for maintaining lens cellular structure, homeostasis, and transparency. Glutathione peroxidase 4 (GPX4), a selenoenzyme, plays a critical role in protecting against lipid peroxidation. This study aims to elucidate the role of GPX4 in lens plasma membrane stability during lens development using in vitro, ex vivo, and in vivo systems. Our findings reveal that GPX4 deficiency triggers lens epithelial apoptosis-independent but ferroptosis-mediated cell death. Blocking lens GPX4 activity during ex vivo culture induces lens opacification, LEC death, and disruption of lens fiber cell arrangement. Deletion of lens-specific Gpx4 results in significant unsaturated phospholipid loss and an increase in oxidized phospholipids. Consequently, lenses with Gpx4 deficiency exhibit massive disruption of lens fiber cell structure, significant loss of LECs via ferroptosis, and formation of newborn cataracts. Remarkably, administering the lipid peroxidation inhibitor, liproxstatin-1, to pregnant mothers at embryonic days 9.5 significantly prevents lipid peroxidation, LEC death, and lens developmental defects. Our study unveils the crucial role of GPX4 in lens development and transparency, and also provides a successful intervention approach to prevent lens developmental defects through lipid peroxidation inhibition.

Iota-Carrageenan from Marine Alga Solieria filiformis Prevents Naproxen-Induced Gastrointestinal Injury via Its Antioxidant and Anti-Inflammatory Activities.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in therapy due to their anti-inflammatory and analgesic properties. However, their clinical use is often associated with gastrointestinal complications. Thus, this study aimed to investigate the protective effect of a sulfated iota-carrageenan isolated from the marine alga Solieria filiformis (IC-Sf) against naproxen-induced gastrointestinal injury. Methods: Parameters of gastrointestinal injury, secretory and motor functions, and toxicity were evaluated. Results: The results demonstrated that IC-Sf significantly reduced naproxen-induced gastrointestinal macroscopic injury, with a maximum effect observed at 30 mg/kg. IC-Sf also preserved gastrointestinal antioxidant defense and prevented lipid peroxidation, with a reduction in the non-protein sulfhydryl group (NP-SH) and malondialdehyde (MDA) concentrations induced by naproxen. Additionally, IC-Sf mitigated naproxen-induced gastrointestinal inflammation, as evidenced by reduced myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). IC-Sf did not alter gastric secretion or gastrointestinal motility. In addition, the animals treated with IC-Sf did not present toxic effects. Conclusions: In conclusion, IC-Sf protected the gastrointestinal tract against the harmful effects of naproxen by inhibiting the inflammatory response and lipid peroxidation, suggesting its potential as a new therapeutic agent or food additive.

Tetranychus ludeni (Acari: Tetranychidae) infestation triggers a spatiotemporal redox response dependent on soybean genotypes.

The redox homeostasis and photosynthetic pigments changes vary with Tetranychus ludeni infestation, with longer-cycle genotypes showing greater tolerance and efficiency in antioxidant defense. Infestations of Tetranychus ludeni Zacher (Tetranychidae) have been frequently observed in soybean plants. In this context, understanding the oscillation of redox homeostasis is crucial for detecting and assessing the stress levels caused in the plants by these organisms. The impacts of these infestations on redox metabolism and photosynthetic pigments are currently unknown. Therefore, we examined the hypothesis that T. ludeni infestations in soybean plants can influence redox homeostasis and photosynthetic pigments in a spatiotemporal manner, varying between different infestation times, modules and genotypes. For this purpose, soybean plants of the genotypes Monsoy, maturity group 5.7, and Brasmax, maturity group 6.3, grown in a controlled environment, were exposed to infestation and evaluated at two periods: 14 and 24days. A variation in the distribution of T. ludeni within the infested plants over time increased the activity of ascorbate peroxidase and catalase, especially in Monsoy, reducing the content of hydrogen peroxide and superoxide, which prevented lipid peroxidation in the apical region in both genotypes. In the basal region, low chlorophyll indices corroborated by the yellow coloration of trifoliate leaves, high levels of membrane stability loss, and accumulation of hydrogen peroxide and superoxide characterized senescent trifoliate leaves in Brasmax, 24days post infestation. Thus, the infestation of T. ludeni has a complex and significant impact on the redox metabolism of soybean plants, especially in shorter-cycle genotypes such as Brasmax. Furthermore, the oscillation of homeostasis can be considered as a good biochemical marker for selecting more suitable genotypes that are less sensitive and prone to infestations.

Antioxidant effects of 2-ethylthiobenzimidazole and a complex of succinic acid salts in rats pre-trained to hypoxia with acute oxygen starvation

BACKGROUND: The body’s response to hypoxia is largely determined by individual sensitivity to it. It has been shown that subjects with high resistance to hypoxia (humans and animals) are less susceptible to the damaging effects of hypoxia on the brain, myocardium, liver, and kidneys. AIM: The experimental study of the antioxidant effects (indicators of lipid peroxidation and the activity of antioxidant systems in the brain) of 2-ethylthiobenzimidazole and a complex of succinic acid salts (amosuccinate) and their combination to increase individual brain resistance to hypoxia during interval hypoxic hypobaric training in rats. MATERIALS AND METHODS: Acute hypoxic hypobaric hypoxia was induced in a flow pressure chamber. Rats were divided according to their resistance to acute hypoxia, raising them in a pressure chamber to a height of 11,000 m at a speed of 50 m/s and exposing them at altitude until agonal breathing occurred. Rats that were exposed to hypoxia for 5–10 minutes were considered low-resistant, and those exposed to hypoxia for more than 10 minutes were considered highly resistant. The interval hypoxic training regimen was 3 days. A one-day training cycle consisted of raising rats 6 times at a speed of 15 m/s to an altitude of 5000 m and exposing them to the height for 30 min. The interval between lifts is 20 minutes. The work used the synthetic adaptogen 2-ethylthiobenzimidazole hydrobromide (metaprot) 25 mg/kg and a complex of succinic acid salts (amosuccinate) 50 mg/kg, which were administered intraperitoneally for 3 days immediately after the end of a one-day training cycle. The control group consisted of trained and untrained rats that received saline. In the brain, the content of lipid peroxidation products (diene conjugates, malonic dialdehyde) was determined and the state of antioxidant systems was assessed (the content of reduced glutathione, the activity of catalase and superoxide dismutase). RESULTS: Acute hypoxia caused excessive lipid peroxidation and decreased activity of antioxidant systems. Metaprot and amosuccinate in combination with hypoxic training prevented lipid peroxidation in the brain of rats. The content of diene conjugates in the brain of rats decreased by 12–26%, malonic dialdehyde by 13–58%. The drugs increased the content of reduced glutathione by 42–76%, catalase by 1.5 times, and superoxide dismutase by 1.5–2.2 times. The effect of the combined use of metaprot with amosuccinate was greater than that of the drugs alone. CONCLUSIONS: The combination of high-altitude training with the use of synthetic alaptogens (metaprote and amosuccinate) increases the adaptive capabilities of the brain, which is confirmed by both an increase in survival time at altitude and a decrease in excessive lipid peroxidation and restoration of antioxidant systems.

The Effects of Dietary Orange Peel Fragments Enriched with Zinc and Vitamins C and E on the Antioxidant and Immune Responses of Nile Tilapia under Stress Conditions.

This study aimed to evaluate the effect of dietary orange peel fragments (OPFs) enriched with vitamins C (C) and E (E), as well as zinc (Zn) on the growth performance, hematological profile, immunological parameters, antioxidant capacity, and fillet lipid peroxidation of Nile tilapia subjected to heat/dissolved oxygen-induced stress (HDOIS), transport-induced stress (TIS), and Aeromonas hydrophila infection (BC). A group of 500 male Nile tilapia (2.7 ± 0.03 g) was randomly distributed in twenty-five 250 L aquaria (20 fish/aquarium) and fed diets containing OPFs (6 g kg-1), OPFs/C (6 g kg-1/1.8 g kg-1), OPFs/E (6 g kg-1/0.4 g kg-1), OPFs/Zn (6 g kg-1/0.21 g kg-1), or OPFs/C/E/Zn (6 g kg-1/1.8 g kg-1/0.4 g kg-1/0.21 g kg-1) for 100 days. The diets were formulated to contain 30% crude protein and 17 MJ kg-1 gross energy. After the feeding period, three groups of fish were independently subjected to a different type of stress: HDOIS (34 °C) for two days; TIS for four hours, or BC for 15 days. The hematological profile, antioxidant capacity, and fillet lipid peroxidation were determined before and after all the stress treatments, along with immunological parameters, which were investigated only for the fish subjected to bacterial infection. In summary, the results showed that growth was not affected by the OPFs, nor by the OPFs enriched with C, E, and Zn; bacterial infection determined anemia for the fish fed any of the experimental diets; the OPFs did not prevent lipid peroxidation under TIS and BC; on the other hand, when enriched with C/E/Zn, lipid peroxidation decreased under HDOIS and TIS. In conclusion, the OPFs enriched with C/E/Zn showed a synergistic effect that promoted an increase in antioxidant enzyme activity, a decrease in lipid peroxidation, and the maintenance of the hematological profile under HDOIS and TIS, but they were not able to maintain the health status under BC.

IL15RA-STAT3-GPX4/ACSL3 signaling leads to ferroptosis resistance in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a poor prognosis, and the lack of effective treatment methods accounts for its high mortality. Pancreatic stellate cells (PSCs) in the tumor microenvironment play an important role in the development of PDAC. Previous studies have reported that patients with PDAC are more vulnerable to ferroptosis inducers. To investigate the relationship between PSCs and pancreatic cancer cells, a coculture system is used to further reveal the influence of PSCs on ferroptosis resistance in PDAC using many in vitro and in vivo experiments. Our results show that PSCs promote ferroptosis resistance in pancreatic cancer cells. We further demonstrate that IL15 secretion by PSCs activates the IL15RA-STAT3-GPX4/ACSL3 axis. The simultaneous upregulation of GPX4 and ACSL3 prevents lipid peroxidation and ultimately protects pancreatic cancer cells from ferroptosis both in vitro and in vivo. This study demonstrates that PSCs protect pancreatic cancer cells in a paracrine manner and may indicate a novel strategy for the treatment of PDAC.

The Biological Effects and Mechanisms of Fisetin on Hepatotoxicity, Liver Injury, and Liver Fibrosis: A Systematic Review

Background: Liver disease is a common cause of death worldwide. Objectives: This study aims to investigate the effects and mechanisms of Fisetin on hepatotoxicity, liver injury, and liver fibrosis. Methods: We adhered to the PRISMA 2020 guidelines in this systematic review. Our search used MeSH keywords encompassed Embase, PubMed, Web of Science, Scopus, and Cochrane Library for articles published before March 2, 2024. Relevant data was extracted from the publications, meticulously recorded in a standard form, and subsequently reviewed for outcomes and mechanisms. Results: Fisetin protects hepatocytes from oxidative stress by neutralizing free radicals (O2 −and H2O2), reduces oxidative stress, prevents lipid peroxidation, and increases endogenous antioxidants. It also reduces inflammation via lowering the production of tumor necrosis factor α (TNF-α), interleukins (IL)1α, IL-6, IL-18, IL-1β suppressing nuclear factor kappa B (NF-κB) activation, and cyclooxygenase- 2 (COX-2), inducible nitric oxide synthase (iNOS) inhibition, reducing monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor 1 (PAI-1), NLR family pyrin domain-containing 3 (NLRP3) inflammasome and interferon-gamma (IFN‐γ). Moreover, it inhibited apoptosis-modulated enzyme activity and detoxification enzymes via modulating the activity of cytochrome P450 and Phase II detoxification enzymes. Fisetin prevented fibrosis by inhibiting the activation of hepatic stellate cells (HSCs), attenuating extracellular matrix (ECM) remodeling-associated genes, and suppressing transforming growth factor-β (TGF-β) signaling pathway and attenuating collagen production. It decreased lipid accumulation and liver function tests. Conclusion: In vivo and in vitro studies indicated that Fisetin can enhance detoxification, attenuate liver injury, and reduce fibrosis, which helps maintain liver health.

Multi-targeted action of rooibos may protect against ischaemic stroke-induced neurological deficit and endothelial dysfunction

Ethnopharmacological relevanceIndigenous use communities in the Western Cape (South Africa) where Aspalathus linearis (Brum.f) R.Dahlgren - or rooibos - grows naturally, has a long history of using rooibos for medicinal purposes. Apart from its well-known antioxidant effect, the Cederberg community in particular has been using rooibos as a treatment for high blood pressure. Given the detrimental effects of high blood pressure on endothelial cells, rooibos may either directly or indirectly affect vascular health. This, together with more recent reports of neuroprotective effects, may position rooibos as complementary medicine in related vascular conditions such as ischaemic stroke. Aims of the studyThe study aimed to evaluate the potential benefit of acute administration of unfermented rooibos, on vascular health in a larval zebrafish model of stroke. Materials and methodsStroke was induced via 24-h ponatinib exposure, in the presence or absence of an aqueous solution of an ethanolic extract of unfermented Rooibos (GreenOxithin™). The magnitude of stroke was assessed by monitoring larval locomotion and thrombus formation. In terms of specific mechanisms probed, changes in redox status (MDA and TEAC), neurological markers (TH and NeuroD1) and endothelial health (tight/adhesion junction protein expression) were assessed. ResultsRooibos treatment limited thrombus formation and prevented stroke-induced deficits on larval motility. In terms of redox status, rooibos treatment prevented lipid peroxidation 3 days after initial stroke induction, reducing the need for significant upregulation of endogenous antioxidant mechanisms. Stroke-induced changes in neuronal (NeuroD1 and TH) protein expression were normalized in the presence of rooibos, suggesting a neuroprotective role. In terms of tight junction proteins, stroke-related decreases in ZO-1 expression were again prevented by rooibos treatment. In addition, rooibos treatment may beneficially modulate levels of claudin-5 and VE-cadherin, to indirectly limit stroke-associated vascular dysfunction. ConclusionsTaken together, activity data and physiological assessments suggest that unfermented rooibos may indeed have benefit in the context of stroke, via action at multiple targets. Thus, current data further our understanding of the mechanisms of actions of rooibos and warrant future research to confirm sufficient bioavailability of rooibos in target tissues, in mammalian systems.

Variation among Blackgram (Vigna mungo L.) Genotypes for Antioxidant Defence System and Yield under High Temperature Stress

Background: Blackgram is a short duration pulse crop which is sensitive to high temperatures. Raising global temperatures are becoming a serious threat to the production of blackgram by altering biochemical processes at cellular level. Hence, the present investigation was carried out for better understanding of genotypic variability and the biochemical mechanisms governing heat stress tolerance which can help in identifying heat tolerant blackgram genotypes that can yield better under climate change scenarios. Methods: Thirty blackgram genotypes selected from temperature induction response technique were evaluated for biochemical efficiency under natural high temperature conditions during summer, 2022 and 23. Field experiment was conducted at Agricultural College Farm, Acharya N.G Ranga Agricultural University, Agricultural College, Bapatla. Biochemical and yield parameters were recorded at flowering and the data were analyzed statistically and pooled. Result: The results of the study revealed that the genotypes TBG-129, LBG-1015, PU-1804 and PU-31 recorded higher seed yield indicating their ability to withstand high temperatures by up-regulating various biochemical pathways involved in increased production of proline, carotenoids and antioxidant defense enzymes that might have scavenged the free radicals that were produced due to high temperature stress, thereby preventing lipid peroxidation. Lower seed yield was recorded in TBG-125 and LBG-1023 which might be due to oxidative damage caused by higher accumulation of free radicals and poor scavenging activity of antioxidant enzymes. Moreover, the results of correlation analysis revealed that all the biochemical traits such as proline, carotenoids and antioxidant defense enzymes showed positive association with seed yield except free radicals and malondialdehyde. The principal component analysis results revealed considerable variability among the traits accounting for 80.0%. The genotypes TBG-129, LBG-1015, PU-1804 and PU-31 can be used in breeding programmes for development of heat tolerant genotypes.

Gpx4 Regulates Invariant NKT Cell Homeostasis and Function by Preventing Lipid Peroxidation and Ferroptosis.

Invariant NKT (iNKT) cells are a group of innate-like T cells that plays important roles in immune homeostasis and activation. We found that iNKT cells, compared with CD4+ T cells, have significantly higher levels of lipid peroxidation in both mice and humans. Proteomic analysis also demonstrated that iNKT cells express higher levels of phospholipid hydroperoxidase glutathione peroxidase 4 (Gpx4), a major antioxidant enzyme that reduces lipid peroxidation and prevents ferroptosis. T cell-specific deletion of Gpx4 reduces iNKT cell population, most prominently the IFN-γ-producing NKT1 subset. RNA-sequencing analysis revealed that IFN-γ signaling, cell cycle regulation, and mitochondrial function are perturbed by Gpx4 deletion in iNKT cells. Consistently, we detected impaired cytokine production, elevated cell proliferation and cell death, and accumulation of lipid peroxides and mitochondrial reactive oxygen species in Gpx4 knockout iNKT cells. Ferroptosis inhibitors, iron chelators, vitamin E, and vitamin K2 can prevent ferroptosis induced by Gpx4 deficiency in iNKT cells and ameliorate the impaired function of iNKT cells due to Gpx4 inhibition. Last, vitamin E rescues iNKT cell population in Gpx4 knockout mice. Altogether, our findings reveal the critical role of Gpx4 in regulating iNKT cell homeostasis and function, through controlling lipid peroxidation and ferroptosis.

Ortho-Vanillin Ameliorates Spinetoram-Induced Oxidative Stress in the Silkworm Bombyx mori: Biochemical and In Silico Insights.

This study investigates the toxic effects of the insecticide spinetoram on the model organism Bombyx mori (Linnaeus) and explores the potential ameliorative properties of O-Vanillin. Sub-lethal concentrations of spinetoram were given to silkworm larvae via oral feed, resulting in reduced body weight, larval length, and impaired cocoon characteristics. A study of the enzymatic and non-enzymatic antioxidants revealed oxidative stress in the gut, fat body, and silk gland tissues, characterized by decreased antioxidants and increased lipid peroxidation. However, post-treatment with O-Vanillin effectively mitigated these toxic effects, preserving antioxidant capacities and preventing lipid peroxidation. Additionally, O-Vanillin prevented the loss of body weight and improved cocoon characteristics. At the histological level, spinetoram exposure caused mild histological damage in the gut, fat body, and silk gland. However, O-Vanillin post-treatment had ameliorative effects and mitigated the histological damages. To delve deeper into the mechanism of amelioration of O-Vanillin, in silico studies were used to study the interaction between an important xenobiotic metabolism protein of theBombyxmori, i.e., Cytochrome p450, specifically CYP9A19, and O-Vanillin. We performed blind molecular docking followed by molecular dynamic simulation, and the results demonstrated stable binding interactions between O-Vanillin and CYP9A19, a cytochrome P450 protein in silkworm, belonging to the subfamily CYP9A, suggesting a potential role for O-vanillin in modulating xenobiotic metabolism.

Metabolomic and biochemical disorders reveal the toxicity of environmental microplastics and benzo[a]pyrene in the marine polychaete Hediste diversicolor

Recently, the abundance of environmental microplastics (MPs) has become a global paramount concern. Besides the danger of MPs for biota due to their tiny size, these minute particles may act as vectors of other pollutants. This study focused on evaluating the toxicity of environmentally relevant concentrations of MPs (10 and 50 mg/kg sediment) and benzo[a]pyrene (B[a]P, 1 µg/kg sediment), alone and in mixture, for 3 and 7 days in marine polychaete Hediste diversicolor, selected as a benthic bioindicator model. The exposure period was sufficient to confirm the bioaccumulation of both contaminants in seaworms, as well as the potential capacity of plastic particles to adsorb and vehiculate the B[a]P. Interestingly, increase of acidic mucus production was observed in seaworm tissues, indicative of a defense response. The activation of oxidative system pathways was demonstrated as a strategy to prevent lipid peroxidation. Furthermore, the comprehensive Nuclear Magnetic Resonance (NMR)-based metabolomics revealed significant disorders in amino acids metabolism, osmoregulatory process, energetic components, and oxidative stress related elements. Overall, these findings proved the possible synergic harmful effect of MPs and B[a]P even in small concentrations, which increases the concern about their long-term presence in marine ecosystems, and consequently their transfer and repercussions on marine fauna.

MLPH is a novel adipogenic factor controlling redox homeostasis to inhibit lipid peroxidation in adipocytes

Abnormal adipose tissue formation is associated with metabolic disorders such as obesity, diabetes, and liver and cardiovascular diseases. Thus, identifying the novel factors that control adipogenesis is crucial for understanding these conditions and developing targeted treatments. In this study, we identified the melanosome-related factor MLPH as a novel adipogenic factor. MLPH was induced during the adipogenesis of 3T3-L1 cells and human mesenchymal stem cells. Although MLPH did not affect lipid metabolism, such as lipogenesis or lipolysis, adipogenesis was severely impaired by MLPH depletion. We observed that MLPH prevented excess reactive oxygen species (ROS) accumulation and lipid peroxidation during adipogenesis and in mature adipocytes. In addition, increased MLPH expression was observed under cirrhotic conditions in liver cancer cells and its overexpression also reduced ROS and lipid peroxidation. Our findings demonstrate that MLPH is a novel adipogenic factor that maintains redox homeostasis by preventing lipid peroxidation and ROS accumulation, which could lead to metabolic diseases.

The Interactive Effects of The Aerobic Exercise and Vitamin E Supplementation on Parkinson's Rat Model.

In Parkinson's disease (PD), mitochondrial defects and oxidative stress cause an increase in free radicals and the death of dopaminergic neurons in the substantia nigra. By preventing lipid peroxidation and protecting against peroxide radicals, vitamin E is the most important antioxidant of biological membranes that can neutralize free radicals. Also, the improvement of the functional status of mitochondria can be influenced by exercise, which can be partially the result of changes in the mitochondrial mitophagy and dynamics system. This study aimed to investigate the interactive effects of six weeks of vitamin E (VE) consumption and training on the mitochondrial function [Cytochrome C (Cyt-C), Adenosine triphosphate (Atp) synthase, optical atrophy1 mitochondrial dynamics like guanosine triphosphatase (GTPase), 8-Oxodequanosin and Pten induced kinase 1 (Pink1) is a protein coding gene] in the hippocampus tissue of PD rats. In this experimental study, 4-6-month-old Sprague-Dawley rats (mean weight 250 ± 30 g) were given parkinsonism with reserpine (2 mg/kg) and were categorized into different groups, including healthy (H), PD, VE solvent+PD (Sham), aerobic exercise+PD (AE+PD), VE+PD, AE+VE+PD. The aerobic training program was carried out for six weeks and 5 sessions per week and each session lasted 15-22 minutes. VE was also taken orally at 30 mg/kg daily. A six-week regimen of VE supplement along with the AE significantly reduced the Cyt-C gene expression level, also we observed a significant increase in gene expression level of the Pink1, Atp synthase and Opa1 (P<0.05). There is no significant difference was found in the level of 8-Oxog detected in hippocampal tissue samples (P>0.05). The consumption of VE along with AE may provide therapeutic effects on mitochondrial damage in PD rats.