Generation Of Oxidative Stress Research Articles

Visible-Light-Responsive Novel Ru(II)-Metallo-Antibiotics with Potential Antibiofilm and Antibacterial Activity.

Growing challenges with antibiotic resistance pose immense challenges in combating microbial infections and biofilm prevention on medical devices. Lately, antibacterial photodynamic therapy (aPDT) is now emerging as an alternative therapy to overcome this problem. Herein, we synthesized and characterized four Ru(II)-complexes, viz., [Ru(ph-tpy)(bpy)Cl]PF6 (Ru1), [Ru(ph-tpy)(dpq)Cl]PF6 (Ru2), [Ru(ph-tpy)(dppz)Cl]PF6 (Ru3), and [Ru(ph-tpy)(dppn)Cl]PF6 (Ru4) (where 4'-phenyl-2,2':6',2″-terpyridine = ph-tpy; 2,2'-bipyridine = bpy; dipyrido[3,2-f:2',3'-h]quinoxaline = dpq; dipyrido[3,2-a:2',3'-c]phenazine = dppz; and Benzo[I]dipyrido[3,2-a:2',3'-c]phenazine = dppn), among which Ru2-Ru4 are novel. Octahedral geometry of the complexes with a RuN5Cl core was evident from the crystal structure of Ru2. Ru1-Ru4 showed an MLCT absorption band in the 450-600 nm region, useful for aPDT performances. Further, optimum triplet excited state energy and excellent photostability of Ru1-Ru4 made them good photosensitizers for aPDT. Ru1-Ru4 demonstrated enhanced antimicrobial activity on visible-light exposure (400-700 nm, 10 J cm-2), confirmed using different antibacterial assays. Mechanistic studies revealed that inhibition of bacterial growth was due to the generation of oxidative stress (via NADH oxidation and ROS generation) upon treatment with Ru2-Ru4, resulting in destruction of the bacterial wall. Ru2 performed best killing performance against both Gram-negative (Escherichia coli) and Gram-positive (Bacillus subtilis) bacteria when exposed to light. Ru2-Ru4, when coated on a polydimethylsiloxane (PDMS) disk, showed long-term reusability and durable antibiofilm properties. Molecular docking confirmed the efficient interaction of Ru2-Ru4 with FabH (regulates fatty acid biosynthesis of E. coli) and PgaB (gives structural stability and helps biofilm formation of E. coli), resulting in probable downregulation. In vivo studies with healthy Wistar rats confirmed the biocompatibility of Ru2. This study shows that these lead complexes (Ru2-Ru4) can be used as potent alternative antimicrobial agents in low concentrations toward bacterial eradication with photodynamic therapy (PDT).

Buparvaquone Induces Ultrastructural and Physiological Alterations Leading to Mitochondrial Dysfunction and Caspase-Independent Apoptotic Cell Death in Leishmania donovani.

Leishmaniasis is a neglected tropical disease (endemic in 99 countries) caused by parasitic protozoa of the genus Leishmania. As treatment options are limited, there is an unmet need for new drugs. The hydroxynaphthoquinone class of compounds demonstrates broad-spectrum activity against protozoan parasites. Buparvaquone (BPQ), a member of this class, is the only drug licensed for the treatment of theileriosis. BPQ has shown promising antileishmanial activity but its mode of action is largely unknown. The aim of this study was to evaluate the ultrastructural and physiological effects of BPQ for elucidating the mechanisms underlying the in vitro antiproliferative activity in Leishmania donovani. Transmission and scanning electron microscopy analyses of BPQ-treated parasites revealed ultrastructural effects characteristic of apoptosis-like cell death, which include alterations in the nucleus, mitochondrion, kinetoplast, flagella, and the flagellar pocket. Using flow cytometry, laser scanning confocal microscopy, and fluorometry, we found that BPQ induced caspase-independent apoptosis-like cell death by losing plasma membrane phospholipid asymmetry and cell cycle arrest at sub-G0/G1 phase. Depolarization of the mitochondrial membrane leads to the generation of oxidative stress and impaired ATP synthesis followed by disruption of intracellular calcium homeostasis. Collectively, these findings provide valuable mechanistic insights and demonstrate BPQ's potential for development as an antileishmanial agent.

Protective Effects of Pear Extract on Skin from In Vitro and In Vivo UVA-Induced Damage.

The ancient Chinese medical book "Compendium of Materia Medica" records that pears can relieve symptoms of respiratory-related diseases. Previous research has shown that pear Pyrus Pyrifolia (Burm.f.) Nakai has antioxidant and anti-inflammatory properties. However, the anti-inflammatory, antioxidant, and anti-photoaging protective effects of Pyrus pyrifolia (Burm.f.) Nakai seed components have not been studied. Ultraviolet light (UV) causes skin inflammation, damages the skin barrier, and is an important cause of skin photoaging. Therefore, UV light with a wavelength of 365 nm was used to irradiate HaCaT and mice. Western blot, real-time quantitative polymerase chain reaction, and fluorescence imaging system were used to explore its anti-UVA mechanism. Dialysis membrane and nuclear magnetic resonance were used for the chemical constituent analysis of pear seed water extract (PSWE). We found that PSWE can significantly reduce UVA-induced skin cell death and mitogen-activated protein kinase phosphorylation and can inhibit the mRNA expression of UVA-induced cytokines (including IL-1β, IL-6, and TNF-α). In addition, PSWE can also reduce the generation of oxidative stress within skin cells. In vivo experimental studies found that PSWE pretreatment effectively reduced transepidermal water loss, inflammation, redness, and dryness in hairless mice. The molecular weight of the active part of pear water extract is approximately 384. Based on the above results, we first found that pear seeds can effectively inhibit oxidative stress and damage caused by UVA. It is a natural extract with antioxidant properties and anti-aging activity that protects skin cells and strengthens the skin barrier.

Toxicity and speciation of inorganic arsenics and their adverse effects on in vivo endpoints and oxidative stress in the marine medaka Oryzias melastigma

Here, we investigate the effects of acute and chronic exposure to arsenate (AsV) and arsenite (AsIII) in the marine medaka Oryzias melastigma. In vivo effects, biotransformation, and oxidative stress were studied in marine medaka exposed to the two inorganic arsenics for 4 or 28 days. An investigation of embryonic development revealed no effect on in vivo parameters, but the hatching rate increased in the group exposed to AsIII. Exposure to AsIII also caused the greatest accumulation of arsenic in medaka. For acute exposure, the ratio of AsV to AsIII was higher than that of chronic exposure, indicating that bioaccumulation of inorganic arsenic can induce oxidative stress. The largest increase in oxidative stress was observed following acute exposure to AsIII, but no significant degree of oxidative stress was induced by chronic exposure. During acute exposure to AsV, the increase in the enzymatic activity of glutathione-S-transferase (GST) was twice as high compared with exposure to AsIII, suggesting that GST plays an important role in the initial detoxification process. In addition, an RNA-seq–based ingenuity pathway analysis revealed that acute exposure to AsIII may be related to cell-cycle progression. A network analysis using differentially expressed genes also revealed a potential link between the generation of inflammatory cytokines and oxidative stress due to arsenic exposure. Environmental implicationArsenic exists in various chemical forms in the environment, and understanding its speciation is crucial for assessing its toxicity. The acute toxicity studies provide insights into the immediate adverse effects, while the chronic toxicity studies shed light on the cumulative and prolonged impacts on fish populations. Recognizing these relationships aids in formulating effective environmental management strategies to mitigate the detrimental effects of arsenic contamination. Therefore, we highlight the broad importance of understanding the interactions between arsenic speciation and toxicity that depend on the duration of exposure in the aquatic environment. Moreover, these findings are important in developing regulatory measures to protect aquatic ecosystems and human health.

Anhydroparthenin as a dual-target inhibitor against Sterol C-24 methyltransferase and Sterol 14-α demethylase of Leishmania donovani: A comprehensive in vitro and in silico study

Parthenium hysterophorus plant has a diverse chemical profile and immense bioactive potential. It exhibits excellent pharmacological properties such as anti-cancer, anti-inflammatory, anti-malarial, microbicidal, and anti-trypanosomal. The present study aims to evaluate the anti-leishmanial potential and toxicological safety of anhydroparthenin isolated from P. hysterophorus. Anydroparthenin was extracted from the leaves of P. hysterophorus and characterized through detailed analysis of 1H, 13C NMR, and HRMS. Dye-based in vitro and ex vivo assays confirmed that anhydroparthenin significantly inhibited both promastigote and amastigote forms of the Leishmania donovani parasites. Both the cytotoxicity experiment and hemolytic assay revealed its non-toxic nature and safety index in the range of 10 to 15. Further, various mechanistic assays suggested that anhydroparthenin led to the generation of oxidative stress, intracellular ATP depletion, alterations in morphology and mitochondrial membrane potential, formation of intracellular lipid bodies, and acidic vesicles, ultimately leading to parasite death. As a dual targeting approach, computational studies and sterol quantification assays confirmed that anhydroparthenin inhibits the Sterol C-24 methyl transferase and Sterol 14-α demethylase proteins involved in the ergosterol biosynthesis in Leishmania parasites. These results suggest that anhydroparthenin could be a promising anti-leishmanial molecule and can be developed as a novel therapeutic stratagem against leishmaniasis.

Redox Pathogenesis in Rheumatic Diseases.

Despite being some of the most anecdotally well-known roads to pathogenesis, the mechanisms governing autoimmune rheumatic diseases are not yet fully understood. The overactivation of the cellular immune system and the characteristic development of autoantibodies have been linked to oxidative stress. Typical clinical manifestations, such as joint swelling and deformities and inflammation of the skin and internal organs, have also been connected directly or indirectly to redox mechanisms. The differences in generation and restraint of oxidative stress provide compelling evidence for the broad variety in pathology among rheumatic diseases and explain some of the common triggers and discordant manifestations in these diseases. Growing evidence of redox mechanisms in pathogenesis has provided a broad array of new potential therapeutic targets. Here, we explore the mechanisms by which oxidative stress is generated, explore its roles in autoimmunity and end-organ damage, and discuss how individual rheumatic diseases exhibit unique features that offer targets for therapeutic interventions.

Biological effects of vanillic acid, iso-vanillic acid, and orto-vanillic acid as environmental pollutants

Vanillic acid (4-hydroxy-3-methoxybenzoic acid) (VA) is a natural benzoic acid derivative commonly found in herbs, rice, maize, and some fruits and vegetables. However, due to the wide use of VA in various industrial sectors, its presence in the environment might harm living organisms. This study evaluated the toxicity of VA and its isomers, iso-VA and orto-VA. Firstly, the antimicrobial effect of VA and its isomers iso-VA and orto-VA (in doses of 1000; 100, 10, 1; 0.1; 0.01 mg/L) against Escherichia coli, Sarcina spp., Enterobacter homaechei, Staphylococcus aureus and Candida albicans were identified. The toxic effect and protein degradation potential of VA and its isomers were determined using E. coli grpE:luxCDABE and lac:luxCDABE biosensor strains. However, the genotoxicity and oxidative stress generation were assessed with the E. coli recA:luxCDABE biosensor and E. coli strain. The results showed that VA, iso-VA, and orto-VA exhibited antimicrobial activity against all tested bacterial strains. However, VA's antimicrobial effect differed from iso-VA and orto-VA. Similar toxic, genotoxic, and oxidative stress-inducing effects were observed for VA and its isomers. Each compound exhibited toxicity, cellular protein degradation, and genotoxic activity against E. coli grpE:luxCDABE, E. coli lac:luxCDABE, and E. coli recA:luxCDABE strains. Analysis of reactive oxygen species (ROS) generation within E. coli cells highlighted oxidative stress as a contributing factor to the toxicity and genotoxicity of VA and its isomers. While the findings suggest potential applications of VA compounds as food preservatives, their presence in the environment raises concerns regarding the risks posed to living organisms due to their toxic and genotoxic characteristics.

Improving Clinical Trials of Antioxidants in Alzheimer's Disease.

Maintaining diversity in drug development in research into Alzheimer's disease (AD) is necessary to avoid over-reliance on targeting AD neuropathology. Treatments that reduce or prevent the generation of oxidative stress, frequently cited for its causal role in the aging process and AD, could be useful in at-risk populations or diagnosed AD patients. However, in this review, it is argued that clinical research into antioxidants in AD could provide more useful feedback as to the therapeutic value of the oxidative stress theory of AD. Improving comparability between randomized controlled trials (RCTs) is vital from a waste-reduction and priority-setting point of view for AD clinical research. For as well as attempting to improve meaningful outcomes for patients, RCTs of antioxidants in AD should strive to maximize the extraction of clinically useful information and actionable feedback from trial outcomes. Solutions to maximize information flow from RCTs of antioxidants in AD are offered here in the form of checklist questions to improve ongoing and future trials centered around the following dimensions: adhesion to reporting guidelines like CONSORT, biomarker enrichment, simple tests of treatment, and innovative trial design.

Intra-uterus phthalate exposure, ROS formation and altered mitochondrial D-loop methylation pattern at birth as potential triggers and markers of Alzheimer’s disease

Alzheimer's Disease is one of the fastest growing causes of dementia, and the factors that trigger its pathology have not yet been completely unraveled. In addition, Alzheimer's disease (AD) impacts not only the individual affected, but also the familial and socio-economic spheres. On the other hand, phthalates are plasticizers capable of interfering with the endocrine system and which, due to the nature of the most varied objects, utensils and tools used by society, as well as the propensity of these chemicals to dissociate from their matrices and accumulate in the environment and living organisms, are frequently and in large quantities exposed to humans. This study explores a possible relationship between exposure to phthalates and the development of Alzheimer's pathophysiology, with emphasis on prenatal exposure and its influence on the risk of dementia in adulthood. Based on the literature consulted, mechanisms for the generation of oxidative stress in the nervous system by phthalates were described and it was proposed how this could be related to the triggering of Alzheimer's pathophysiology, primarily in view of the modification of the methylation pattern of mitochondrial DNA. In addition, it was observed that exposure to phthalates during intrauterine life is capable of generating changes in the epigenetic pattern at birth. An alternative for the early detection of mitochondrial metabolic dysfunctions, which could potentially evolve into dementia, could involve monitoring D-loop methylation levels. Therefore, we hypothesized that intrauterine exposure to phthalates may generate oxidative stress in the brain and alter the mtDNA methylation pattern, which can perturb mitochondrial function and increase risk of development of AD at adulthood. We suggest that these phthalate-induced metabolic changes may be detected by the D-loop methylation pattern at birth. We highlight the need for more research integrating the emerging fields of mitoepigenetics and bioenergetic medicine with neurodegenerative diseases, and an experimental design employing zebrafish as a model is suggested to test the hypotheses raised.

Protective effect of Ganoderma lucidum-fermented crop extracts against hydrogen peroxide- or β-amyloid-induced damage in human neuronal SH-SY5Y cells

BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of stacked β-amyloid peptides in the brain and associated with the generation of oxidative stress. So far, there is no cure for AD or a way to stop its progression. Although the neuroprotective effects of Ganoderma lucidum aqueous extract and G. lucidum-derived triterpenoids and polysaccharides have been reported, the influence of G. lucidum-fermented crops on AD still lacks clarity.MethodsThis study aimed to investigate the protective effect of G. lucidum-fermented crop extracts against hydrogen peroxide- or β-amyloid peptide (Aβ25-35)-induced damage in human neuroblastoma SH-SY5Y cells.ResultsVarious extracts of G. lucidum-fermented crops, including extract A: 10% ethanol extraction using microwave, extract B: 70˚C water extraction, and extract C: 100˚C water extraction followed by ethanol precipitation, were prepared and analyzed. Extract B had the highest triterpenoid content. Extract C had the highest total glucan content, while extract A had the highest gamma-aminobutyric acid (GABA) content. The median inhibitory concentration (IC50, mg/g) for DPPH and ABTS scavenging activity of the fermented crop extracts was significantly lower than that of the unfermented extract. Pretreatment with these extracts significantly increased the cell viability of SH-SY5Y cells damaged by H2O2 or Aβ25-35, possibly by reducing cellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Moreover, extract B markedly alleviated the activity of acetylcholinesterase (AChE), which is crucial in the pathogenesis of AD.ConclusionThese results clearly confirmed the effects of G. lucidum-fermented crop extracts on preventing against H2O2- or Aβ25-35-induced neuronal cell death and inhibiting AChE activity, revealing their potential in management of AD.

Curcumin coating: a novel solution to mitigate inherent carbon nanotube toxicity

Multi-walled Carbon Nanotubes (MWCNTs) are inert structures with high aspect ratios that are widely used as vehicles for targeted drug delivery in cancer and many other diseases. They are largely non-toxic in nature however, when cells are exposed to these nanotubes for prolonged durations or at high concentrations, they show certain adverse effects. These include cytotoxicity, inflammation, generation of oxidative stress, and genotoxicity among others. To combat such adverse effects, various moieties can be attached to the surface of these nanotubes. Curcumin is a known anti-inflammatory, antioxidant and cytoprotective compound derived from a medicinal plant called Curcuma longa. In this study, we have synthesized and characterized Curcumin coated-lysine functionalized MWCNTs and further evaluated the cytoprotective, anti-inflammatory, antioxidant and antiapoptotic effect of Curcumin coating on the surface of MWCNTs. The results show a significant decrease in the level of inflammatory molecules like IL-6, IL-8, IL-1β, TNFα and NFκB in cells exposed to Curcumin-coated MWCNTs as compared to the uncoated ones at both transcript and protein levels. Further, compared to the uncoated samples, there is a reduction in ROS production and upregulation of antioxidant enzyme-Catalase in the cells treated with Curcumin-coated MWCNTs. Curcumin coating also helped in recovery of mitochondrial membrane potential in the cells exposed to MWCNTs. Lastly, cells exposed to Curcumin-coated MWCNTs showed reduced cell death as compared to the ones exposed to uncoated MWCNTs. Our findings suggest that coating of Curcumin on the surface of MWCNTs reduces its ability to cause inflammation, oxidative stress, and cell death.Graphical (a) Synthesis of Curcumin-coated-Lysine-functionalized MWCNTs. (b) Flow of research depicting experimental groups and studies performed along with the underlying techniques used.

Study of Oxidative Stress and Inflammatory Status in Thyroid Dysfunction: A Systematic Review

Background: The frequency of thyroid disorders is rising quickly, making them a major socioeconomic issue. Oxidative stress is also connected to thyroid disorders with increasing frequency. Moreover, an association between underlying inflammatory processes and oxidative damage must be considered because most thyroid ailments are seen to have an underlying inflammatory basis. Aim & objectives: This systematic review assesses the oxidative stress in thyroid dysfunctions and their association with inflammatory processes. Methodology: A systematic review of the literature was done using databases that included- PubMed, Scopus, Science Direct, Research Gate and Google Scholar using the keywords “oxidative stress”, “inflammatory markers,” and “thyroid disorders” from 2000-2022. After separately evaluating citations and abstracts, two reviewers examined full-text publications and came to an agreement on the research that should be included. We conducted this research using the preferred reporting items for systematic research and meta-analysis (PRISMA). Results: A total of 531 articles were found, out of which only 51 met the criteria of inclusion. A significant heterogeneity across the studies was found. In these studies, various oxidant/antioxidant and inflammatory markers were used to determine oxidative stress and its association with inflammatory processes. Most studies found a high level of reactive oxygen species (ROS) induced by an imbalance of thyroid hormones that can cause oxidative stress with a consequent lipid peroxidation response and accelerated inflammatory response. Conclusion: Data from the literature demonstrated a significant correlation between oxidative damage results and elevated ROS production. Thyroid issues can potentially trigger or exacerbate oxidative stress and ROS generation, which can worsen oxidative damage. Additionally, recent research indicates that OS and inflammation may be related in some way since mitochondrial reactive species are signalling molecules that cause the release of proinflammatory cytokines

Abstract 1477: Acrylamide exposure in obesity enhances mammary epithelial DNA damage via the activity of its metabolite, glycidamide, and increased oxidative stress

Abstract Obesity is a world-wide epidemic, with 39% of adults considered overweight and 13% obese, and rates are rising. Obese women are at greater risk for developing breast cancer than lean women, however the mechanisms of how obesity increases breast cancer risk are not well understood. There is also limited knowledge on how environmental toxins may interact with obesity to promote breast cancer. Acrylamide, a probable carcinogen, is a biproduct in starchy foods cooked at high temperatures, which are prevalent in the obesity-inducing Western diet. Acrylamide is metabolized by the CYP2E1 enzyme into the epoxide, glycidamide, which is known to induce DNA damage. CYP2E1 activity is elevated in obesity, which could enhance DNA damage in obese individuals. Acrylamide exposure is associated with an increased risk of breast cancer in epidemiologic studies, but the evidence has been contradictory. To investigate how acrylamide impacts DNA damage in the obese mammary gland, three-week-old FVB female mice were randomized to receive a low-fat (LFD; 16% kcal from fat) or high-fat diet (HFD; 60% kcal from fat) and either 0.7 mM acrylamide water or control water. HFD-fed mice gained significantly more weight than LFD-fed mice, and exposure to acrylamide did not impact weight gain compared to respective controls. Mammary epithelial cells from acrylamide-treated mice had increased DNA damage compared to controls measured by COMET assays, with the highest DNA damage present in epithelial cells from obese acrylamide-treated mice. Mammary epithelial cells from acrylamide-treated mice also had enhanced oxidative DNA damage, measured by 8-OHdG adducts, and an additive effect was observed between acrylamide exposure and obesity. To investigate the impact of acrylamide in vitro, COMMA-D mammary epithelial cells were treated with vehicle, 9.8 µM acrylamide, or 0.5 mM glycidamide for 24 hours, then COMET assays and immunohistochemistry for markers of DNA damage were performed. COMMA-D cells treated with acrylamide-metabolite glycidamide showed significantly increased double strand DNA breaks compared to vehicle-treated cells, however acrylamide-treated cells did not. Interestingly, acrylamide-treated cells demonstrated significantly higher levels of intracellular reactive oxygen species compared to both glycidamide and vehicle-treated cells. These studies suggest acrylamide exposure enhances DNA damage in mammary epithelial cells via conversion to the genotoxic metabolite glycidamide and through generation of oxidative stress, which is exacerbated by obese conditions. These studies suggest that long-term acrylamide exposure through foods common in the Western diet may enhance DNA damage in mammary epithelial cells, potentially enhancing obesity-induced breast cancer risk. Citation Format: Brenna Walton, Lisa Arendt. Acrylamide exposure in obesity enhances mammary epithelial DNA damage via the activity of its metabolite, glycidamide, and increased oxidative stress [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1477.

Orientin Promotes Antioxidant Capacity, Mitochondrial Biogenesis, and Fiber Transformation in Skeletal Muscles through the AMPK Pathway.

The sleep-breathing condition obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse, which can exacerbate oxidative stress and free radical generation, thereby detrimentally impacting both motor and sensory nerve function and inducing muscular damage. OSA development is promoted by increasing proportions of fast-twitch muscle fibers in the genioglossus. Orientin, a water-soluble dietary C-glycosyl flavonoid with antioxidant properties, increased the expression of slow myosin heavy chain (MyHC) and signaling factors associated with AMP-activated protein kinase (AMPK) activation both in vivo and in vitro. Inhibiting AMPK signaling diminished the effects of orientin on slow MyHC, fast MyHC, and Sirt1 expression. Overall, orientin enhanced type I muscle fibers in the genioglossus, enhanced antioxidant capacity, increased mitochondrial biogenesis through AMPK signaling, and ultimately improved fatigue resistance in C2C12 myotubes and mouse genioglossus. These findings suggest that orientin may contribute to upper airway stability in patients with OSA, potentially preventing airway collapse.

Berberine modulates cardiovascular diseases as a multitarget-mediated alkaloid with insights into its downstream signals using in silico prospective screening approaches

Atherosclerosis is potentially correlated with several cardiac disorders that are greatly associated with cellular oxidative stress generation, inflammation, endothelial cells dysfunction, and many cardiovascular complications. Berberine is a natural isoquinoline alkaloid compound that widely modulates pathogenesis of atherosclerosis through its different curative potentials. This in silico screening study was designed to confirm the potent restorative properties of berberine chloride as a multitarget-mediated alkaloid against the CVDs and their complications through screening, identifying, visualizing, and evaluating its binding models, affinities, and interactions toward several CVDs-related targets as direct and/or indirect-mediated signals via inhibiting cellular ER stress and apoptotic signals and activating autophagy pathway. The drug-likeness properties of berberine were predicted using the computational QSAR/ADMET and Lipinski’s RO5 analyses as well as in silico molecular docking simulations. The potent berberine-binding modes, residues-interaction patterns, and free energies of binding scores towards several CVDs-related targets were estimated using molecular docking tools. Furthermore, the pharmacokinetic properties and toxicological features of berberine were clearly determined. According to this in silico virtual screening study, berberine chloride could restore cardiac function and improve pathogenic features of atherosclerotic CVDs through alleviating ER stress and apoptotic signals, activating autophagy, improving insulin sensitivity, decreasing hyperglycemia and dyslipidemia, increasing intracellular RCT signaling, attenuating oxidative stress and vascular inflammation, and upregulating cellular antioxidant defenses in many cardiovascular tissues. In this in silico study, berberine chloride greatly modulated several potent CVDs-related targets, including SIGMAR1, GRP78, CASP3, BECN1, PIK3C3, SQSTM1/p62, LC3B, GLUT3, INSR, LDLR, LXRα, PPARγ, IL1β, IFNγ, iNOS, COX-2, MCP-1, IL10, GPx1, and SOD3.

Effects of Different Capsulotomy and Fragmentation Energy Levels on the Generation of Oxidative Stress Following Femtosecond Laser-Assisted Cataract Surgery.

This study was conducted to evaluate the effects of different capsulotomy and fragmentation energy levels on the production of oxidative free radicals following femtosecond laser-assisted cataract surgery (FLACS) with a low-energy platform. The experimental study included 60 porcine eyes (12 groups). In each group, capsulotomies with 90% or 150% energy, and fragmentations with 90%, 100%, or 150% energy or 150% with high spot density, respectively, were performed. Control samples were obtained from non-lasered eyes at the beginning (five eyes) and end (five eyes) of the experiment. In the clinical study, 104 eyes were divided into 5 groups, and they received conventional phacoemulsification (20 eyes), FLACS with 90% capsulotomy and 100% fragmentation energy levels without NSAIDs (16 eyes), FLACS with 90% (26 eyes) or 150% (22 eyes) capsulotomy energy levels, respectively, with a 100% fragmentation energy level and NSAIDs, and FLACS with 90% capsulotomy and 150% fragmentation energy levels and NSAIDs (20 eyes). Aqueous samples were analyzed for their malondialdehyde (MDA) and superoxide dismutase (SOD) levels. In the experimental study, there were no significant differences in the MDA and SOD levels between the groups with different capsulotomy energy levels. An increase in the fragmentation energy from 100% to 150% led to significantly higher MDA levels in the groups with both 90% (p = 0.04) and 150% capsulotomy energy levels (p = 0.03), respectively. However, increased laser spot densities did not result in significant changes in MDA or SOD levels. In the clinical study, all four of the FLACS groups showed higher MDA levels than the conventional group. Similarly, the increase in the fragmentation energy from 100% to 150% resulted in significantly elevated levels of MDA and SOD, respectively. Although increasing the FSL capsulotomy energy level may not have increased free radicals, higher fragmentation energy levels increased the generation of aqueous free radicals. However, fragmentation with high spot density did not generate additional oxidative stress. Increased spot density did not generate additional oxidative stress, and this can be helpful for dense cataracts.

Effect of Arthrospira (Spirulina) maxima on Cadmium-Chloride-Induced Alterations in Sexual Behavior and Fertility in Male Wistar Rats.

Chronic exposure to potentially toxic elements (PTEs) such as cadmium (Cd) leads to male reproductive toxicity through the generation of oxidative stress. Spirulina Arthrospira maxima (AM) is a cyanobacterium that has been consumed since ancient times for its high nutritional value, and in recent years for its antiviral, hepatoprotective, hypoglycemic, anticancer, and antioxidant effects, among others. This study aimed to evaluate the effects of AM against the damage to reproductive health induced by Cd. A total of 48 10-week-old sexually experienced male Wistar rats were distributed in five groups (n = 8): control; vehicle (tween-water); cadmium chloride (CdCl2) 5 mg/kg; and three doses of AM (100, 200 and 400 mg/kg) + CdCl2 5 mg/kg. All treatments were orally administered once a day for 36 consecutive days. At the end, sexual behavior was evaluated, and semen, testicle, and blood samples were obtained to analyze sperm quality, enzymatic activity, and testosterone levels, respectively. Rats exposed to Cd showed a decrease in sexual behavior, as well as in the quality of reproductive health, and an increase in oxidative stress; while rats exposed simultaneously to AM + Cd showed an improvement in all this parameters. Based on our results, we believe that the mechanism by which AM exerts its effect could be attributed to the presence of phycobiliproteins. These compounds are responsible for exerting an antioxidant effect and chelating effect on elements such as Cd.

Lead induced genotoxicity and hepatotoxicity in zebrafish (Danio rerio) at environmentally relevant concentration: Nrf2-Keap1 regulated stress response and expression of biomarker genes

Genotoxic and hepatotoxic potentials of Pb at an environmentally relevant concentration (5 ppm) in zebrafish were investigated in the present study. Erythrocytic nuclear abnormality tests revealed the increased frequencies of abnormal erythrocytes after Pb exposure, indicating a strong genotoxic potential of Pb. Multiple stress-related parameters were further evaluated in liver, the major detoxifying organ. Pb caused increased production of ROS, which in turn caused severe oxidative stress. As a result, lipid peroxidation was increased, whereas reduced glutathione level and catalase activity was decreased. Alterations in liver histoarchitecture also served as evidence of Pb-induced hepatotoxicity. Pb-induced ROS stress triggered upregulation of Nrf2, Nqo1, Ho1; downregulation of Keap1, and altered mRNA expressions of Mn-sod, Cu/Zn-sod, gpx1, cyp1a, ucp2 suggesting involvement of Nrf2-Keap1-ARE signaling in cellular defence. Nrf2-keap1 is a sensitive biomarker of Pb-induced ROS stress. Overexpression of Hsp70 and other genes in hepatocytes might help cell survival under oxidative stress generation.

Michelia compressa-Derived Santamarine Inhibits Oral Cancer Cell Proliferation via Oxidative Stress-Mediated Apoptosis and DNA Damage.

The anti-oral cancer effects of santamarine (SAMA), a Michelia compressa var. compressa-derived natural product, remain unclear. This study investigates the anticancer effects and acting mechanism of SAMA against oral cancer (OC-2 and HSC-3) in parallel with normal (Smulow-Glickman; S-G) cells. SAMA selectively inhibits oral cancer cell viability more than normal cells, reverted by the oxidative stress remover N-acetylcysteine (NAC). The evidence of oxidative stress generation, such as the induction of reactive oxygen species (ROS) and mitochondrial superoxide and the depletion of mitochondrial membrane potential and glutathione, further supports this ROS-dependent selective antiproliferation. SAMA arrests oral cancer cells at the G2/M phase. SAMA triggers apoptosis (annexin V) in oral cancer cells and activates caspases 3, 8, and 9. SAMA enhances two types of DNA damage in oral cancer cells, such as γH2AX and 8-hydroxy-2-deoxyguanosine. Moreover, all of these anticancer mechanisms of SAMA are more highly expressed in oral cancer cells than in normal cells in concentration and time course experiments. These above changes are attenuated by NAC, suggesting that SAMA exerts mechanisms of selective antiproliferation that depend on oxidative stress while maintaining minimal cytotoxicity to normal cells.

Generation of oxidative stress in freshwater oligochaete Tubifex tubifex due to exposure to aniline: time and concentration dependent toxicity assessment

ABSTRACT Our current study examines the significant impact of aniline on the fish feed freshwater benthic annelid, Tubifex tubifex, including mortality, changes in total protein concentration and antioxidant enzyme activity (catalase, superoxide dismutase, glutathione-s transferase and glutathione peroxidase), as well as the generation of oxidative stress (by assessing malondialdehyde concentration). The 96-hour LC50 value of aniline is 276.940 mg/L. The General Unified Threshold Model of Survival (GUTS) was used to validate the survival rate pattern of the test organism in response to aniline at the acute level, with the GUTS-SD model better correctly predicting the expected course of population death. During long-term bioassay antioxidant enzymes activities (superoxide dismutase, glutathione-s transferase and glutathione peroxidase) and oxidative stress biomarkers concentration (malondialdehyde concentration) is substantially enhanced while protein concentration and Catalase activity are markedly reduced during the bioassay. The stress and detrimental effects of aniline on Tubifex tubifex were examined in the current study, taking into account all biomarkers, by utilising the Integrated Biomarker Response index. The results show that exposure to toxicants like aniline has a detrimental effect on Tubifex tubifex's survival rate and general health.