Increased Lipid Peroxidation Research Articles

MVP enhances FGF21-induced ferroptosis in hepatocellular carcinoma by increasing lipid peroxidation through regulation of NOX4.

Ferroptosis is a novel, iron-dependent regulatory cell death mainly caused by an imbalance between the production and degradation of intracellular reactive oxygen species (ROS). Recently, ferroptosis induction has been considered a potential therapeutic approach for hepatocellular carcinoma (HCC). Fibroblast growth factor 21 (FGF21) is a new modulator of ferroptosis; however, the regulatory role of FGF21 in HCC ferroptosis has not been investigated. In this study, we explored the role of FGF21 and its underlying molecular mechanism in the ferroptotic death of HCC cells. We identified Major vault protein (MVP) as a target of FGF21 and revealed that knockdown of MVP inhibited the lipid peroxidation levels of HCC cells by decreasing NADPH oxidase 4 (NOX4, a major source of ROS) transcription, thereby attenuating the effect of FGF21-mediated ferroptosis. On the other hand, MVP overexpression showed the opposite results. Mechanistically, MVP binds to IRF1 and thus interferes with the interaction between IRF1 and the YAP1 promoter, leading to an increase in NOX4 transcription. Importantly, forced expression of IRF1 or downregulation of YAP1 partially reversed the effect of MVP overexpression on HCC ferroptosis. Furthermore, the results in xenograft tumor models suggested that overexpression of MVP can efficiently increase the level of lipid peroxidation invivo. Taken together, these results provide new insights into the regulatory mechanism of ferroptosis in HCC.

The ectomycorrhizal fungus Paxillus involutus positively modulates Castanea sativa Miller (var. Marsol) responses to heat and drought co-exposure

Castanea sativa Miller, a high-valuable crop for Mediterranean countries, is facing frequent and prolonged periods of heat and drought, severely affecting chestnut production. Aiming to tackle this problem, this study unraveled the influence of mycorrhizal association with the fungi Paxillus involutus (Batsch) on young chestnut plants' responses to combined heat (42 °C; 4 h/day) and drought (no irrigation until soil moisture reached 25%) over 21 days of stress exposure. Heat stress had no harmful effects on growth, photosynthesis, nor induced oxidative stress in either mycorrhizal (MR) or non-mycorrhizal (NMR) chestnut plants. However, drought (alone or combined) reduced the growth of NMR plants, affecting water content, leaf production, and foliar area, while also hampering net CO2 assimilation and carbon relations. The mycorrhizal association, however, mitigated the detrimental effects of both stresses, resulting in less susceptibility and fewer growth limitations in MR chestnut plants, which were capable of ensuring a proper carbon flow. Evaluation of the oxidative metabolism revealed increased lipid peroxidation and hydrogen peroxide levels in NMR plants under water scarcity, supporting their higher susceptibility to stress. Conversely, MR plants activated defense mechanisms by accumulating antioxidant metabolites (ascorbate, proline and glutathione), preventing oxidative damage, especially under the combined stress. Overall, drought was the most detrimental condition for chestnut growth, with heat exacerbating stress susceptibility. Moreover, mycorrhizal association with P. involutus substantially alleviated these effects by improving growth, water relations, photosynthesis, and activating defense mechanisms. Thus, this research highlights mycorrhization's potential to enhance C. sativa resilience against climate change, especially at early developmental stages.

Bromodomain-containing protein 4 knockdown promotes neuronal ferroptosis in a mouse model of subarachnoid hemorrhage.

Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage. Neuronal ferroptosis in particular plays an important role in early brain injury. Bromodomain-containing protein 4, a member of the bromo and extraterminal domain family of proteins, participated in multiple cell death pathways, but the mechanisms by which it regulates ferroptosis remain unclear. The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro. Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons, and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo. In addition, ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage. Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis. Using cleavage under targets and tagmentation analysis, we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro. Furthermore, treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074, a Raf-1 inhibitor, exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway. Moreover, targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage. Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage, and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.

Hemin-Induced Transient Senescence Via DNA Damage Response: A Neuroprotective Mechanism Against Ferroptosis in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) poses acute fatality and long-term neurological risks due to hemin and iron accumulation from hemoglobin breakdown. Our observation that hemin induces DNA double-strand breaks (DSBs), prompting a senescence-like phenotype in neurons, necessitating deeper exploration of cellular responses. Using experimental ICH models and human ICH patient tissue, we elucidate hemin-mediated DNA damage response (DDR) inducing transient senescence and delayed expression of heme oxygenase (HO-1). HO-1 co-localizes with senescence-associated β-Galactosidase (SA-β-Gal) in ICH patient tissues, emphasizing clinical relevance of inducible HO-1 expression in senescent cells. We reveal a reversible senescence state protective against acute cell death by hemin, while repeat exposure leads to long-lasting senescence. Inhibiting early senescence expression increases cell death, supporting the protective role of senescence against hemin toxicity. Hemin-induced senescence is attenuated by a pleiotropic carbon nanoparticle that is a catalytic mimic of superoxide dismutase, but this treatment increased lipid peroxidation, consistent with ferroptosis from hemin breakdown released iron. When coupled with iron chelator deferoxamine (DEF), the nanoparticle reduces hemin-induced senescence and upregulates factors protecting against ferroptosis. Our study suggests transient senescence induced by DDR as an early potential neuroprotective mechanism in ICH, but the risk or iron-related toxicity supports a multi-pronged therapeutic approach.

Sequential Administration of Febuxostat, Amlodipine and Vitamin E Attenuate Oxidative Stress and Improve Spermatogenesis in Testicular Ischemia Reperfusion Injury in Wistar Rats

This study investigated the effects of sequential administration of febuxostat, amlodipine, and vitamin E on oxidative stress and spermatogenesis following testicular ischemia-reperfusion injury (TIRI) in Wistar rats. Ninety male rats (120-150 g) were divided into 9 groups (n=10 each): sham operation (SO), torsion-detorsion (TD), and seven treatment groups receiving different combinations of the drugs. The treatment groups included torsion + febuxostat + detorsion (TFD), torsion + detorsion + amlodipine (TDA), torsion + detorsion + vitamin E (TDV), and combinations thereof (TFDA, TFDV, TDAV, TFDAV). TIRI was induced by 720° clockwise testicular torsion for 1 hour followed by detorsion. Febuxostat (5 mg/kg) was administered 30 minutes after torsion, amlodipine (2.5 mg/kg) immediately upon detorsion, and vitamin E (10 mg/kg) 30 minutes after detorsion. Rats were sacrificed 56 days post-reperfusion. Testicular tissue was analyzed for antioxidant enzymes (superoxide dismutase, catalase), lipid peroxidation (malondialdehyde), total protein, inflammatory markers (serum nitrite, IL-1β), and spermatogenesis indices (testicular biopsy score, Leydig cell count). Results showed that TIRI significantly decreased antioxidant enzymes, significantly increased lipid peroxidation and inflammatory markers, and impaired spermatogenesis. In the TD group, superoxide dismutase (SOD) and catalase (CAT) activities were significantly decreased, while malondialdehyde (MDA) increased significantly compared to the SO group (p<0.01). Serum nitrite and IL-1β levels in the TD group were also increased (p<0.001). Furthermore, the testicular biopsy score and Leydig cell count in the TD group were significantly decreased in this study (p<0.01). Sequential administration of febuxostat, amlodipine and vitamin E, particularly when all three were used (TFDAV group), significantly attenuated these changes. In the TFDAV group, SOD and CAT activities were improved, while MDA decreased compared to the TD group (p<0.05). Serum nitrite and IL-1β levels in the TFDAV group were also decreased (p<0.001). In addition, the testicular biopsy score and Leydig cell count in the TFDAV group increased in comparison with the TD group (p<0.001). The study concludes that this sequential multi-drug approach shows promise in mitigating the long-term detrimental effects of TIRI on testicular function and fertility. The combination of febuxostat (a xanthine oxidase inhibitor), amlodipine (a calcium channel blocker), and vitamin E (an antioxidant) appears to provide protection against oxidative stress and inflammation induced by TIRI, thereby preserving spermatogenesis.

In-depth transcriptome and physiological function analysis reveals the toxicology of sodium fluoride in the fall webworm Hyphantria cunea

Fluoride is an environmental pollutant that severely injures various organisms in ecosystems. Herein, the non-target organism, fall webworm (Hyphantria cunea), was used to determine the toxicological mechanism of NaF exposure. In this study, H. cunea exposed to NaF showed significant declines in growth and reproduction. The authors conducted RNA sequencing on adipose bodies and midgut tissues from NaF-exposed H. cunea larvae to uncover the toxicological mechanisms. The results showed that extracellular matrix-receptor interaction, pentose and glucuronate interconversions, fatty acid biosynthesis, and ferroptosis might contribute to NaF stress. NaF significantly decreased the antioxidant level, nitrous oxide synthase activity, and NO content, while significantly increasing lipid peroxidation. NaF induced significant changes in the expression of energy metabolism genes. However, the triglyceride content was significantly decreased and the lipase enzyme activity was significantly increased. Moreover, the expression levels of light and heavy chains of ferritin were inhibited in NaF-exposed H. cunea. NaF caused ferritin Fe2+overload in FerHCH1 and FerLCH knockdown H. cunea larvae, activated reactive oxygen species, and reduced the total iron content, eventually increasing the mortality H. cunea larvae. This study identified the toxicological mechanisms of NaF in lipid synthesis and energy metabolism in H. cunea, providing a basis for understanding the molecular mechanisms of NaF toxicity and developing pollution control strategies.

Radiation-Induced Endothelial Ferroptosis Accelerates Atherosclerosis via the DDHD2-Mediated Nrf2/GPX4 Pathway.

This study sought to explore potential roles of endothelial ferroptosis in radiation-associated atherosclerosis (RAA) and molecular mechanisms behind this phenomenon. Here, an in vivo RAA mouse model was used and treated with ferroptosis inhibitors. We found that the RAA group had a higher plaque burden and a reduction in endothelial cells with increased lipid peroxidation compared to the control group, while ameliorated by liproxstatin-1. In vitro experiments further confirmed that radiation induced the occurrence of ferroptosis in human artery endothelial cells (HAECs). Then, proteomics analysis of HAECs identified domain-containing protein 2 (DDHD2) as a co-differentially expressed protein, which was enriched in the lipid metabolism pathway. In addition, the level of lipid peroxidation was elevated in DDHD2-knockdown HAECs. Mechanistically, a significant decrease in the protein and mRNA expression of glutathione peroxidase 4 (GPX4) was observed in HAECs following DDHD2 knockdown. Co-immunoprecipitation assays indicated a potential interaction between DDHD2 and nuclear factor erythroid 2-related factor 2 (Nrf2). The downregulation of Nrf2 protein was also detected in DDHD2-knockdown HAECs. In conclusion, our findings suggest that radiation-induced endothelial ferroptosis accelerates atherosclerosis, and DDHD2 is a potential regulatory protein in radiation-induced endothelial ferroptosis through the Nrf2/GPX4 pathway.

Medicinal evaluation and molecular docking study of osajin as an anti-inflammatory, antioxidant, and antiapoptotic agent against sepsis-associated acute kidney injury in rats

Despite efforts to find effective drugs for sepsis-associated acute kidney injury (SA-AKI), mortality rates in patients with SA-AKI have not decreased. Our study evaluated the protective effects of isoflavone osajin (OSJ) on SA-AKI in rats by targeting inflammation, oxidative stress, and apoptosis, which represent the cornerstones in the pathophysiological mechanism of SA-AKI. Polymicrobial sepsis was induced in rats via the cecal ligation and puncture (CLP) technique. Markers of oxidative stress were evaluated in kidney tissues using biochemical methods. The expression of interleukin-33 (IL-33), 8-hydroxydeoxyguanosine (8-OHdG), caspase-3, and kidney injury molecule-1 (KIM-1) was evaluated as indicators of inflammation, DNA damage, apoptosis, and SA-AKI respectively in the kidney tissues using immunohistochemical and immunofluorescent detection methods. The CLP technique significantly (p < 0.001) increased lipid peroxidation (LPO) levels and significantly (p < 0.001) decreased the activities of superoxide dismutase and catalase in kidney tissues. In the renal tissues, strong expression of IL-33, 8-OHdG, caspase-3, and KIM-1 was observed with severe degeneration and necrosis in the tubular epithelium and intense interstitial nephritis. In contrast, the administration of OSJ significantly (p < 0.001) reduced the level of LPO, markedly improved biomarkers of antioxidant status, decreased the levels of serum creatinine and urea, lowered the expression of IL-33, 8-OHdG, caspase-3, and KIM-1 and alleviated changes in renal histopathology. A promising binding score was found via a molecular docking investigation of the OSJ-binding mode with mouse IL-33 (PDB Code: 5VI4). Therefore, OSJ protects against SA-AKI by suppressing the IL-33/LPO/8-OHdG/caspase-3 pathway and improving the antioxidant system.

Internalization of nano- and micro-plastics in human erythrocytes leads to oxidative stress and estrogen receptor-mediated cellular responses

Plastic material versatility has resulted in a substantial increase in its use in several sectors of our everyday lives. Consequently, concern regarding human exposure to nano-plastics (NPs) and micro-plastics (MPs) has recently increased. It has been shown that plastic particles entering the bloodstream may adhere to the erythrocyte surface and exert adverse effects following erythrocyte aggregation and adhesion to blood vessels. Here, we explored the effects of polystyrene nano-plastics (PS-NPs) and micro-plastics (PS-MPs) on human erythrocytes. Cellular morphology, binding/internalization of PS-NPs and PS-MPs, oxidative stress parameters, as well as the distribution and anion exchange capability of band 3 (anion exchanger 1; SLC4A1) have been analyzed in human erythrocytes exposed to 1 μg/mL PS-NPs or PS-MPs for 3 and 24 h, respectively. The data obtained showed significant modifications of the cellular shape after exposure to PS-NPs or PS-MPs. In particular, a significantly increased number of acanthocytes, echinocytes and leptocytes were detected. However, the percentage of eryptotic cells (<1 %) was comparable to physiological conditions. Analytical cytology and confocal microscopy showed that PS-NPs and PS-MPs bound to the erythrocyte plasma membrane, co-localized with estrogen receptors (Erα/ERβ), and were internalized. An increased trafficking from the cytosol to the erythrocyte plasma membrane and abnormal distribution of ERs were also observed, consistent with ERα-mediated binding and internalization of PS-NPs. An increased phosphorylation of ERK1/2 and AKT kinases indicated that an activation of the ER-modulated non-genomic pathway occurred following exposure to PS-NPs and PS-MPs. Interestingly, PS-NPs or PS-MPs caused a significant production of reactive oxygen species, resulting in an increased lipid peroxidation and protein sulfhydryl group oxidation. Oxidative stress was also associated with an altered band 3 ion transport activity and increased oxidized haemoglobin, which led to abnormal clustering of band 3 on the plasma membrane. Taken together, these findings identify cellular events following the internalization of PS-NPs or PS-MPs in human erythrocytes and contribute to elucidating potential oxidative stress-related harmful effects, which may affect erythrocyte and systemic homeostasis.

The role of lipid peroxidation in epithelial–mesenchymal transition of retinal pigment epithelial cells

Epithelial–Mesenchymal Transition (EMT) of retinal pigment epithelial (RPE) cells is recognized as pivotal in various retinal diseases. Previous studies have suggested a reciprocal regulation between reactive oxygen species (ROS) and EMT, though the involvement of peroxidized lipids or the effects of reducing them has remained unclear. The present study disclosed that EMT of ARPE-19 cells induced by TGF-β2 and TNF-α involves increased lipid peroxidation, and Ferrostatin-1 (Fer-1), a lipophilic antioxidative agent, successfully inhibited the increase in lipid peroxidation. Fer-1 suppressed the formation of EMT-associated fibrotic deposits, while EMT induction or Fer-1 treatment did not influence the cell viability or proliferation. Functionally, Fer-1 impeded EMT-driven cell migration and reduction in transepithelial electrical resistance. It demonstrated regulatory prowess by downregulating the mesenchymal marker fibronectin, upregulating the epithelial marker ZO-1, and inhibiting the EMT-associated transcriptional factor ZEB1. Additionally, VEGF, a major pathogenic cytokine in various retinal diseases, is also upregulated during EMT, and Fer-1 significantly mitigated the effect. The present study disclosed the involvement of lipid peroxidation in EMT of RPE cells, and suggests the suppression of lipid peroxidation may be a potential therapeutic target in retinal diseases in which EMT is implicated.

Ecotoxicological Research on the Toxic Impact of Zinc Oxide and Silver Nanoparticles on Oreochromis mossambicus.

Silver nanoparticles (AgNPs) and Zinc oxide nanoparticles (ZnONPs) have been widely used and are eventually been discharged into the natural aquatic ecosystem. The current study examined and correlated the toxicity of AgNPs and ZnONPs on the Mozambique tilapia, Oreochromis mossambicus. Lethal concentration (LC50) was determined with four different concentrations (0.05, 0.10, 0.15, and 0.20 mg/L) of AgNPs and ZnONPs; subsequently, the fishes were exposed to sublethal concentrations for a period of 21 days, and the oxidative stress and antioxidant and nonantioxidant parameters were studied. Results revealed oxidative stress evinced by increased lipid peroxidation (LPO) protein carbonyl activity (PCA), glutathione-S-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) activity, metallothionein (MT) activity, and reduced glutathione in chronic exposure compared with acute exposure. Nonspecific immunological characteristics such as lysozyme (LYZ), myeloperoxidase (MPO), and respiratory burst activity (RBA) were also noticed in the serum. Furthermore, severe histological damages including damages in telangiectasia and epithelial cell hyperplasia were found in the combined treated group with Ag and ZnONPs than in individual treatments. When Ag and ZnONPs were combined, a reduction in the accumulation of Ag was observed in the liver, which increased drastically in individual exposure. The current findings highlight the importance of taking into account the combined exposure and correlation of NPs, their bioavailability, and toxicity in the aquatic ecosystem.

Ferroptosis: a novel strategy to overcome chemoresistance in gynecological malignancies.

Ferroptosis is an iron-dependent form of cell death, distinct from apoptosis, necrosis, and autophagy, and is characterized by altered iron homeostasis, reduced defense against oxidative stress, and increased lipid peroxidation. Extensive research has demonstrated that ferroptosis plays a crucial role in the treatment of gynecological malignancies, offering new strategies for cancer prevention and therapy. However, chemotherapy resistance poses an urgent challenge, significantly hindering therapeutic efficacy. Increasing evidence suggests that inducing ferroptosis can reverse tumor resistance to chemotherapy. This article reviews the mechanisms of ferroptosis and discusses its potential in reversing chemotherapy resistance in gynecological cancers. We summarized three critical pathways in regulating ferroptosis: the regulation of glutathione peroxidase 4 (GPX4), iron metabolism, and lipid peroxidation pathways, considering their prospects and challenges as strategies to reverse chemotherapy resistance. These studies provide a fresh perspective for future cancer treatment modalities.

GRP75-dependent mitochondria-ER contacts ensure cell survival during early mouse thymocyte development

Mitochondria and endoplasmic reticulum contacts (MERCs) control multiple cellular processes, including cell survival and differentiation. Based on the observations that MERCs were specifically enriched in the CD4-CD8- double-negative (DN) stage, we studied their role in early mouse thymocyte development. We found that Tcell-specific knockout of Hspa9, which encodes GRP75, a protein that mediates MERC formation by assembling the IP3R-GRP75-VDAC complex, impaired DN3 thymocyte viability and resulted in thymocyte developmental arrest at the DN3-DN4 transition. Mechanistically, GRP75 deficiency induced mitochondrial stress, releasing mitochondrial DNA (mtDNA) into the cytosol and triggering the type I interferon (IFN-I) response. The IFN-I pathway contributed to both the impairment of cell survival and DN3-DN4 transition blockage, while increased lipid peroxidation (LPO) played a major role downstream of IFN-I. Thus, our study identifies the essential role of GRP75-dependent MERCs in early thymocyte development and the governing facts of cell survival and differentiation in the DN stage.

Hematological and neurological impact studies on the exposure to naturally occurring radioactive materials

Naturally Occurring Radioactive Materials (NORM) contribute to everyone's natural background radiation dose. The technologically advanced activities of the gas and oil sectors produce considerable amounts of radioactive materials as industrial by-products or waste products. The goal of the current study is to estimate the danger of long-term liability to Technologically Enhanced Naturally Occurring Radioactive Materials (TE-NORM) on blood indices, neurotransmitters, oxidative stress markers, and β-amyloid in the cerebral cortex of rats' brains. Twenty adult male albino rats were divided into two equal groups (n = 10): control and irradiated. Irradiated rats were exposed to a total dose of 0.016 Gy of TE-NORM as a whole-body chronic exposure over a period of two months. It should be ''The results showed no significant changes in RBC count, Hb concentration, hematocrit percentage (HCT%), and Mean Corpuscular Hemoglobin Concentration (MCHC). However, there was a significant increase in the Mean Corpuscular Volume of RBCs (MCV) and a significant decrease in cell distribution width (RDW%) compared to the control. Alteration in neurotransmitters is noticeable by a significant increase in glutamic acid and significant decreases in serotonin and dopamine. Increased lipid peroxidation, decreased glutathione content, superoxide dismutase, catalase, and glutathione peroxidase activities indicating oxidative stress were accompanied by increased β-amyloid in the cerebral cortex of rats' brains. The findings of the present study showed that chronic radiation liability has some harmful effects, that may predict the risks of future health problems in occupational radiation exposure in the oil industries. Therefore, the control of exposure and application of sample dosimetry is recommended for health and safety.

Loss of β-catenin reveals a role for glutathione in regulating oxidative stress during cholestatic liver disease.

Cholestasis is an intractable liver disorder that results from impaired bile flow. We have previously shown that the Wnt/β-catenin signaling pathway regulates the progression of cholestatic liver disease through multiple mechanisms, including bile acid metabolism and hepatocyte proliferation. To further explore the impact of these functions during intrahepatic cholestasis, we exposed mice to a xenobiotic that causes selective biliary injury. α-naphthylisothiocyanate (ANIT) was administered to liver-specific knockout (KO) of β-catenin and wild-type mice in the diet. Mice were killed at 6 or 14 days to assess the severity of cholestatic liver disease, measure the expression of target genes, and perform biochemical analyses. We found that the presence of β-catenin was protective against ANIT, as KO mice had a significantly lower survival rate than wild-type mice. Although serum markers of liver damage and total bile acid levels were similar between KO and wild-type mice, the KO had minor histological abnormalities, such as sinusoidal dilatation, concentric fibrosis around ducts, and decreased inflammation. Notably, both total glutathione levels and expression of glutathione-S-transferases, which catalyze the conjugation of ANIT to glutathione, were significantly decreased in KO after ANIT. Nuclear factor erythroid-derived 2-like 2, a master regulator of the antioxidant response, was activated in KO after ANIT as well as in a subset of patients with primary sclerosing cholangitis lacking activated β-catenin. Despite the activation of nuclear factor erythroid-derived 2-like 2, KO livers had increased lipid peroxidation and cell death, which likely contributed to mortality. Loss of β-catenin leads to increased cellular injury and cell death during cholestasis through failure to neutralize oxidative stress, which may contribute to the pathology of this disease.

Flaxseed Oil, Casitose, and Its Combination Diets Increase Antioxidant Activity and Upregulates Aging-related Genes in Drosophila melanogaster

Abstract Background: Nutrigenomics refers to the study of how diet influences the genomic expression and function of an organism. Diet is a significant factor that impacts metabolism, aging, and lifespan. Long-term dietary patterns can influence the risk of age-related diseases, including diabetes, cardiovascular diseases, hypertension, and cancer. While research in Drosophila melanogaster has focused on areas such as calorie restriction, high-sugar and high-fat diets, micronutrients, and disease-specific nutritional interventions, the effects of different combinations of macronutrients have not been adequately studied. This study aimed to analyze the impact of individual macronutrients, specifically flaxseed oil (a source of fat) and casitose (hydrolyzed milk protein), as well as their combinations, on longevity, antioxidant activity, and the expression of aging-related genes in D. melanogaster. Methods: The study examined the in vivo effects of different concentrations of flaxseed oil (120 μl, 240 μl, 480 μl, and 960 μl), casitose (125 mg, 250 mg, 500 mg, and 1000 mg), and their combinations with a base diet on longevity, antioxidant activity, and the expression of aging-related genes, namely manganese superoxide dismutase (Mn-SOD or SOD1) and copper–zinc SOD (Cu-Zn SOD or SOD2) in D. melanogaster. Results: The study found that flaxseed oil, casitose, and their combinations increased lipid peroxidation (LPO) activity, leading to the production of reactive oxygen species. However, these substances also enhanced the activity of the antioxidant enzymes SOD and catalase, which help combat-free radicals. Furthermore, the gene expression of SOD1 and SOD2 was upregulated, suggesting a potential mechanism for the observed improvements in lifespan. Interestingly, high doses of flaxseed oil (960 μl) were associated with decreased lifespan in the flies. Conclusion: The findings indicate that the optimal levels of flaxseed oil, casitose, or their combination can increase lifespan in Drosophila by upregulating the expression of the antioxidant enzymes SOD1 and SOD2. This provides insights into the potential of targeted nutrient combinations as a dietary approach to combat aging-related diseases.

Embryonic ethanol exposure induces oxidative stress and inflammation in zebrafish model: A dose-dependent study

Alcohol, or ethanol, is a major contributor to detrimental diseases and comorbidities worldwide. Alcohol use during pregnancy intervenes the developing embryos leading to morphological changes, neurocognitive defects, and behavioral changes known as fetal alcohol spectrum disorder (FASD). Zebrafish have been used as a model to study FASD; however, the mechanism and the impact of ethanol on oxidative stress and inflammation in the zebrafish FASD model remain unexplored. Hence, we exposed zebrafish embryos to different concentrations of ethanol (0 %, 0.5 %, 1.0 %, 1.25 %, and 1.5 % ethanol (v/v)) at 4–96 hours post-fertilization (hpf) to study and characterize the ethanol concentration for the FASD model to induce oxidative stress and inflammation. Here, we studied the survival rate and developmental toxicity parameters at different time points and measured oxidative stress, reactive oxygen species (ROS) generation, apoptosis, and pro-inflammatory gene expression in zebrafish larvae. Our findings indicate that ethanol causes various developmental abnormalities, including decreased survival rate, spontaneous tail coiling, hatching rate, heart rate, and body length, associated with increased malformation. Further, ethanol exposure induced oxidative stress by increasing lipid peroxidation and nitric oxide production and decreasing glutathione levels. Subsequently, ethanol increased ROS generation, apoptosis, and pro-inflammatory gene (TNF-α and IL-1β) expression in ethanol exposed larvae. 1.25 % and 1.5 % ethanol had significant impacts on zebrafish larvae in all studied parameters. However, 1.5 % ethanol showed decreased survival rate and increased malformations. Overall, 1.25 % ethanol is the ideal concentration to study the oxidative stress and inflammation in the zebrafish FASD model.

Comparative study on biochemical responses to imidacloprid and clothianidin in cockroaches (Blattella germanica)

AbstractCockroaches, ubiquitous pests known for significant reproduction and as potential vectors of diseases, are notorious for their adoptability to a variety of insecticides that cause substantial challenges in pest control. The present research evaluated the LC50 concentrations of imidacloprid (0.65 mg/L) and clothianidin (2.5 μg/L) for Blattella germanica using topical and bait methods. The cockroaches were exposed to one‐third concentration of LC50 at a regular interval of 1, 2, 4, 8, 12, 16 and 20 days. During exposure, the activity of P450 monooxygenase increased, whereas the activity of brain acetylcholinesterase decreased. Lactate dehydrogenase, alkaline and acid phosphatase activity were highest on day 4, with a slight recovery on day 20. The elevated activities for superoxide dismutase and catalase, as well as increased lipid peroxidation levels on day 4, followed by a significant recovery in activity on day 20. The glutathione‐S‐transferase activity was elevated while the glutathione content was reduced, and a significant restoration was observed at the end of the experiment. The biochemical mechanisms of the organisms such as P450, esterase enzymes and oxidative systems, are actively involved in the detoxification mechanism. The study elucidated that the insecticide defence mechanism triggers detoxification pathways that encompass the metabolism of endogenous insecticidal compounds, with clothianidin showing greater efficacy and lower detoxification compared with imidacloprid.

C-Phycocyanin Prevents Oxidative Stress, Inflammation, and Lung Remodeling in an Ovalbumin-Induced Rat Asthma Model.

Asthma is a chronic immunological disease related to oxidative stress and chronic inflammation; both processes promote airway remodeling with collagen deposition and matrix thickening, causing pulmonary damage and lost function. This study investigates the immunomodulation of C-phycocyanin (CPC), a natural blue pigment purified from cyanobacteria, as a potential alternative treatment to prevent the remodeling process against asthma. We conducted experiments using ovalbumin (OVA) to induce asthma in Sprague Dawley rats. Animals were divided into five groups: (1) sham + vehicle, (2) sham + CPC, (3) asthma + vehicle, (4) asthma + CPC, and (5) asthma + methylprednisolone (MP). Our findings reveal that asthma promotes hypoxemia, leukocytosis, and pulmonary myeloperoxidase (MPO) activity by increasing lipid peroxidation, reactive oxygen and nitrogen species, inflammation associated with Th2 response, and airway remodeling in the lungs. CPC and MP treatment partially prevented these physiological processes with similar action on the biomarkers evaluated. In conclusion, CPC treatment enhanced the antioxidant defense system, thereby preventing oxidative stress and reducing airway inflammation by regulating pro-inflammatory and anti-inflammatory cytokines, consequently avoiding asthma-induced airway remodeling.

A comparative study between curcumin and curcumin nanoparticles on reproductive performance and antioxidant system of aged roosters

Increased lipid peroxidation and decreased antioxidant status can result in reduced reproductive activity and fertility in aged male broiler breeders. This study was conducted to evaluate the effects of curcumin supplements (natural or nanoparticles) on the sperm characteristics, antioxidant system, fertility, and hatchability of aged roosters (54-64 wk), and to estimate the relative bioavailability value (RBV) of nano-curcumin on the measured parameters including the hypo-osmotic swelling test (HOST), motility, viability, sperm count, volume, the concentration of testosterone, glutathione peroxidase (GPx), and superoxide dismutase (SOD), diameter of the spermatogenic tube (DST), epithelium thickness (EpiTh), spermatogonia count (SPcount), fertility, hatchability, and relative weight of testis (RW-testis). A total of 30 roosters were individually caged and randomly assigned to 5 treatments comprising control (without curcumin as the basal diet), basal diet + 15 mg/kg curcumin (CUR15), basal diet + 30 mg/kg curcumin (CUR30), basal diet + 15 mg/kg nano-curcumin (Nano15), and basal diet + 30 mg/kg nano-curcumin (Nano30) for 10 wk. The slope ratio method was used to estimate the bioavailability of nano-curcumin by regressing each response on supplemental curcumin intake. Increasing dietary curcumin (P < 0.001) elicited a linear response to all studied traits. The RBV for volume, viability, motility, HOST, RW-testis, and GPx were estimated as 135 (CI: 115-156%), 143 (CI: 114-173%), 159 (CI: 122-196%), 132 (CI: 107-157%), 195 (CI: 126-264%), 176 (CI: 103-249%), and 178% (28-328%), respectively. Our findings revealed that curcumin nanoparticles enhance the reproductive efficiency of aged breeder roosters. In addition, the curcumin nanoparticles RBV exceeded that of natural curcumin, suggesting that lower concentrations of curcumin nanoparticles could have a significant effect on reproductive characteristics.