Lipid Peroxidation Alterations Research Articles

Mutagenicity of the agriculture pesticide chlorothalonil assessed by somatic mutation and recombination test in Drosophila melanogaster.

Chlorothalonil (CTL) is a pesticide widely used in Brazil, yet its mutagenic potential is not fully determined. Thus, we assessed the mutagenicity of CTL and its bioactivation metabolites using the somatic mutation and recombination test (SMART) in Drosophila melanogaster, by exposing individuals, with basal and high bioactivation capacities (standard and high bioactivation cross offspring, respectively), from third instar larval to early adult fly stages, to CTL-contaminated substrate (0.25, 1, 10 or 20 μM). This substrate served as food and as physical medium. Increased frequency of large single spots in standard cross flies' wings exposed to 0.25 μM indicates that, if CTL is genotoxic, it may affect Drosophila at early life stages. Since the total spot frequency did not change, CTL cannot be considered mutagenic in SMART. The same long-term exposure design was performed to test whether CTL induces oxidative imbalance in flies with basal (wild-type, WT) or high bioactivation (ORR strain) levels. CTL did not alter reactive oxygen species and antioxidant capacity against peroxyl radicals levels in adult flies. However, lipid peroxidation (LPO) levels were increased in WT male flies exposed to 1 μM CTL. SMART and LPO alterations were observed only in flies with basal bioactivation levels, pointing to direct CTL toxicity to DNA and lipids. Survival, emergence and locomotor behavior were not affected, indicating no bias due to lethality, developmental and behavioral impairment. We suggest that, if related to CTL exposure, DNA and lipid damages may be residual damage of earlier life stages of D. melanogaster.

Unravelling bisphenol A-induced hepatotoxicity: Insights into oxidative stress, inflammation, and energy dysregulation

Bisphenol A (BPA), a prevalent plastic monomer and endocrine disruptor, negatively impacts metabolic functions. This study examines the chronic effects of eco-relevant BPA concentrations on hepatotoxicity, focusing on redox balance, inflammatory response, cellular energy sensors, and metabolic homeostasis in male Swiss albino mice. Chronic BPA exposure resulted in reactive oxygen species (ROS) accumulation, altered hepatic antioxidant defense, lipid peroxidation, and NOX4 expression, leading to reduced cell viability. Additionally, BPA exposure significantly upregulated hepatic pro-inflammatory cytokine genes (Tnf-α, Il-1β, Il-6), NOS2, and arginase II, correlating with increased TLR4 expression, NF-κB phosphorylation, and a dose-dependent decrease in IκBα levels. BPA-induced NF-κB nuclear localization and inflammasome activation (NLRP3, cleaved caspase-1, IL-1β) established an inflammatory milieu. Perturbations in hepatic AMPKα phosphorylation, SIRT1, and PGC-1α, along with elevated p38 MAPK phosphorylation and ERα expression, indicated BPA-induced energy dysregulation. Furthermore, increased PLA2G4A, COX1, COX2, and PTGES2 expression in BPA-treated liver correlated with hyperlipidemia, hepatic FASN expression, steatosis, and visceral adiposity, likely due to disrupted energy sensors, oxidative stress, and inflammasome activation. Elevated liver enzymes (ALP, AST, ALT) and apoptotic markers indicated liver damage. Notably, N-acetylcysteine (NAC) priming reversed BPA-induced hepatocellular ROS accumulation, NF-κB-inflammasome activation, and intracellular lipid accumulation, while upregulating cellular energy sensors and attenuating ERα expression, suggesting NAC's protective effects against BPA-induced hepatotoxicity. Pharmacological inhibition of the NF-κB/NLRP3 cascade in BAY11-7082 pretreated, or NLRP3 immunodepleted hepatocytes reversed BPA's negative impact on SIRT1/p-AMPKα/PGC-1α and intracellular lipid accumulation, providing mechanistic insights into BPA-induced metabolic disruption.

Biochemical and Histoarchitectural evaluation of 4-Vinylcyclohexane induced ovarian cancer against Alpinia purpurata (Vieill). K. Schum

ObjectiveAlpinia purpurata is being studied for its potential to treat various conditions, including diabetes, arthritis, and tuberculosis. This research explores the impact of Alpinia purpurata (Vieill). K. Schum on ovarian cancer induced by 4-vinyl cyclohexane in Wistar albino rats. Materials and methodsFive sets of 100–120 g Wistar albino rats were assembled. Group 1 was the control group. Group 2 received intraperitoneal injection of 4-vinyl cyclohexane (80 mg/kg) for one month. Group 3 Treated similarly to Group 2 subsequently for the next two months treated with oral administration of A. purpurata ethyl acetate leaf extract (200 mg/kg body weight) Group 4 Treated similarly to Group subsequently for the next two months treated with Standard Drug Cisplatin (5 mg/kg body weight) weekly twice intraperitoneally. Group 5 acquired daily oral A. purpurata leaf extract (200 mg/kg) for two months. The rats were euthanized after the experiment under light chloroform anesthesia. Ovary and liver samples were obtained for lipid peroxidation, anti-oxidants, membrane-bound enzymes, tumor indicators, and histological investigation. ResultsOver a 60-day period, rats were given an ethyl acetate extract of A. purpurata at a dose of 200 mg/kg, which lead to in a substantial (p < 0.05) increase in body protein content, as well as enzyme levels. Furthermore, the use of the ethyl acetate extract significantly (p < 0.05) recovered the altered lipid peroxidation activities in the ovarian tissues of both control and experimental rats to near-normal levels. These data imply that the extract has the capacity to quench free radicals, indicating possible anticancer effects. ConclusionThe results suggested that, the ethyl acetate extract of A. purpurata exhibited significant antitumor activity against 4-vinyl cyclohexane induced ovarian cancer bearing rats.

Cucurbitacin B and erastin co-treatment synergistically induced ferroptosis in breast cancer cells via altered iron-regulating proteins and lipid peroxidation

Ferroptosis is a unique type of cell death which co-exists with elevated iron, suppressed antioxidative function and increased lipid peroxidation. Recent studies have shown that cancer cells are particularly susceptible to the compounds with ferroptotic activities. Cucurbitacin B (CuB) is a triterpenoid with potent biological properties. It has been demonstrated to induce apoptosis and inhibit metastasis in cancer cells. However, the underlying mechanism of the compound is still not fully understood. In the present study, we investigated the ferroptotic effect of CuB in breast cancer cells and evaluated the impact of its combination with erastin, a ferroptosis inducer. In this regard, MTT assay was performed to analyze cell viability. Lipid peroxidation, oxidative stress and the cellular antioxidant capacity were determined with relevant kits. The expression of ferroptotic proteins were analyzed by western blotting. The results indicated that the combined treatment of CuB and erastin activated the ferroptotic pathways significantly in MCF-7 and MDA-MB-231 breast cancer cells. More importantly, the combination treatment altered the expression of iron-related proteins IREB2 and FPN1. In conclusion, this study demonstrated the ferroptotic potential of CuB in breast cancer cells for the first time, and revealed its impact on the expression of iron-regulating proteins.

Sodium Selenate, Potassium Hydroxy-Selenide, Acetylselenide and Their Effect on Antioxidant Metabolism and Plant Nutrition and Yield in Sorghum Genotypes.

Agronomic biofortification with selenium (Se) effectively reduces hidden hunger and increases the nutritional intake of Se in people and animals. Because sorghum is a staple diet for millions of people and is used in animal feed, it becomes a crop with biofortification potential. Consequently, this study aimed to compare organoselenium compounds with selenate, which is effective in numerous crops, and to assess grain yield, the effect in the antioxidant system, and macronutrient/micronutrient contents of different sorghum genotypes treated with Se, via foliar spray. The trials used a 4 × 8 factorial design, with four Se sources (control-without Se supply, sodium selenate, potassium hydroxy-selenide, acetylselenide) and eight genotypes (BM737, BRS310, Enforcer, K200, Nugrain320, Nugrain420, Nugrain430, and SHS410). The Se rate used was 0.125 mg plant-1. All genotypes reacted effectively to foliar fertilization with Se through sodium selenate. In this experiment, potassium hydroxy-selenide and acetylselenide showed low Se levels and lower Se uptake and absorption efficiency than selenate. Selenium fertilization increased grain yield and altered lipid peroxidation by malondialdehyde content, hydrogen peroxide content, catalase activity, ascorbate peroxidase, superoxide dismutase, and macronutrients and micronutrients content of the studied genotypes. In sum, biofortification with selenium led to an overall yield increase of sorghum plants and supplementation with selenium through sodium selenate was more efficient than organoselenium compounds, yet acetylselenide had a positive effect on the antioxidant system. Sorghum can be effectively biofortified through the foliar application of sodium selenate; however, studying the interaction between organic and inorganic Se compounds in plants is necessary.

PERIODONTAL DISEASE AND SALIVARY OXIDATION STRESS IN CHILDREN WITH LYMPHOGRANULOMATOSIS.

The aim: To investigate the impact of lymphogranulomatosis (LGM) and periodontal disease on salivary lipid peroxidation and enzymatic antioxidants` levels in children. Materials and methods: 45 children aged 6-16 years with LGM were examined before hematologic therapy (group LGM 1), after therapy (group LGM 2), and at the remission (group LGM 3). The control group included 70 healthy children. Periodontal state of children, saliva thiobarbituric acid reacting substances (TBARS), superoxide dismutase (SOD) and catalase were examined. Results: 6-11 years old children from LGM 1 group showed a higher frequency of periodontal disease (50,0%), as well as 12-15 year olds (80,8%) compared to healthy children (17,4% and 42,8% accordingly, p<0,05). TBARS levels were higher in LGM 1-3 groups of children with periodontal disease (9,79, 12,3 and 12,6 umol/l, р<0,01) compared to counterparts without it (8,01, 10,1 and 11,6 umol/l, р<0,01) and healthy children with periodontal disease (7,9 umol/l, р<0,01). SOD activity was higher in LGM 1-3 groups of children with periodontal disease (-0,075, -0,086, -0,074 units) compared to children without it (-0,048, -0,059, -0,04 units, р<0,01) and healthy children with periodontal disease (-0,04 units, р<0,01). Catalase activity was lower in LGM 1-3 groups of children with periodontal disease (6,72, 5,2 and 6,7 units) compared to counterparts without it (7,3, 3,7 and 4,7 units, р<0,01) and healthy children with periodontal disease (7,1 units, р<0,01). Conclusions: Children with periodontal disease related to LGM had higher TBARS levels, SOD activity and lower catalase activity in saliva. Both LGM and periodontal disease altered lipid peroxidation and antioxidant protection in saliva of children.

Mitochondria as multifaceted regulators of ferroptosis

AbstractMitochondria are well known to be “energy factories” of the cell as they provide intracellular ATP via oxidative phosphorylation. Interestingly, they also function as a “cellular suicidal weapon store” by acting as a key mediator of various forms of regulated cell death, including apoptosis, pyroptosis, necroptosis, and ferroptosis. Ferroptosis, distinct from the other types of regulated cell death, is characterized by iron-dependent lipid peroxidation and subsequent plasma membrane rupture. Growing evidence suggests that an impaired ferroptotic response is implicated in various diseases and pathological conditions, and this impaired response is associated with dramatic changes in mitochondrial morphology and function. Mitochondria are the center of iron metabolism and energy production, leading to altered lipid peroxidation sensitivity. Although a growing number of studies have explored the inextricable link between mitochondria and ferroptosis, the role of this organelle in regulating ferroptosis remains unclear. Here, we review recent advances in our understanding of the role of mitochondria in ferroptosis and summarize the characteristics of this novel iron-based cellular suicide weapon and its arsenal. We also discuss the importance of ferroptosis in pathophysiology, including the need for further understanding of the relationship between mitochondria and ferroptosis to identify combinatorial targets that are essential for the development of successful drug discovery.

Role of Oxidative Stress in the Disruption of the Endothelial Apical Junctional Complex During Corneal Cold Storage.

Purpose: To characterize the impact of corneal cold storage (CS) on the endothelial apical junctional complex (AJC). Methods: Porcine corneas were held in CS (4°C; 1-7 days) with Cornisol™ preservation medium supplemented with epothilone B (EpoB; microtubule stabilizer; 100 nM), SB-203580 (p38 mitogen-activated protein [MAP] kinase inhibitor; 20 μM), or antioxidants (quercetin, 100 μM; vitamin E, 1 mM; deferoxamine, an iron chelator, 10 mM). After CS termination, the damage to endothelial AJC was characterized by imaging perijunctional actomyosin ring (PAMR) and zonula occludens (ZO-1). The effects of EpoB and SB-203580 were characterized by imaging microtubules. The loss in the barrier function was assessed in cultured cells grown on biotin-coated gelatin by permeability to fluorescein isothiocyanate (FITC)-avidin. The accumulation of reactive oxygen species (ROS), altered mitochondrial membrane potential (MMP), lipid peroxidation, and lactate dehydrogenase (LDH) release were also determined in response to CS. Results: CS led to the loss of microtubules, destruction of PAMR, and breakdown of ZO-1 in the endothelium. The severity of damage increased when CS was prolonged. Although rewarming of the tissue increased the damage, the effect was marginal. CS also induced accumulation of ROS, alteration in MMP, lipid peroxidation, enhanced LDH release, and increased permeability to FITC-avidin. These changes were opposed by EpoB, SB-203580, and antioxidants. Conclusion: Corneal CS destroys AJC of the endothelium, leading to loss of its barrier function. The effects were surmounted by microtubule stabilization, p38 MAP kinase inhibition, and antioxidants. Thus, there is potential for reformulation of the preservation medium to maintain the health of the donor corneal endothelium before transplantation.

Diet and Obesity-Induced Methylglyoxal Production and Links to Metabolic Disease.

The obesity rate in the United States is 42.4% and has become a national epidemic. Obesity is a complex condition that is influenced by socioeconomic status, ethnicity, genetics, age, and diet. Increased consumption of a Western diet, one that is high in processed foods, red meat, and sugar content, is associated with elevated obesity rates. Factors that increase obesity risk, such as socioeconomic status, also increase consumption of a Western diet because of a limited access to healthier options and greater affordability of processed foods. Obesity is a public health threat because it increases the risk of several pathologies, including atherosclerosis, diabetes, and cancer. The molecular mechanisms linking obesity to disease onset and progression are not well understood, but a proposed mechanism is physiological changes caused by altered lipid peroxidation, glycolysis, and protein metabolism. These metabolic pathways give rise to reactive molecules such as the abundant electrophile methylglyoxal (MG), which covalently modifies nucleic acids and proteins. MG-adducts are associated with obesity-linked pathologies and may have potential for biomonitoring to determine the risk of disease onset and progression. MG-adducts may also play a role in disease progression because they are mutagenic and directly impact protein stability and function. In this review, we discuss how obesity drives metabolic alterations, how these alterations lead to MG production, the association of MG-adducts with disease, and the potential impact of MG-adducts on cellular function.

Enzyme activity and expression of catalases in response to oxidative stress in Sporothrix schenckii

Sporothrix schenckii is a dimorphic fungus, pathogenic to humans and animals, which is usually infective in the yeast form. Reactive oxygen species (ROS) play an important role in the host's defense, damaging the pathogen's DNA, proteins, and lipids. To prevent oxidative damage, the ROS are detoxified by pathogen-derived antioxidant enzymes such as catalases (CATs). In this work, we analyzed the activity and expression level of three S. schenckii genes, designated as CAT1, CAT2, and CAT3, that putatively encoded for three isoforms of monofunctional CAT with a predicted molecular weight of 57.6, 56.2, and 81.4 kDa, respectively. Our results demonstrate that oxidative stress induced by exogenous H2O2 leads to an altered lipid peroxidation, modifying CAT activity and the expression levels of the CAT genes, being CAT1 and CAT3 the genes with the highest expression in response to the oxidizing agent. These results show that CAT isoforms in S. schenckii can be regulated in response to oxidative stress and might help to control ROS homeostasis in the fungus-host interaction.

The pro-apoptotic and cytotoxic efficacy of polydatin encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles

Polydatin (POL) is an ingredient of many herbal medications and has pharmacological properties. The present study aimed to determine the antitumor potential of Polydatin loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (POL-PLGA-NPs) against the cancerous KB cell line. We evaluated the efficiency of synthesized nanoparticles on cell proliferation and apoptosis markers, in addition to the generation of reactive oxygen species (ROS) and its potential to induce damages on the mitochondrial membrane. Morphological changes in the cells (damage to DNA incurred due to cell lysis) were observed under Ethidium Bromide and Acridine orange staining techniques. The results evidenced the loss of cell viability, increased ROS, altered lipid peroxidation levels, increased DNA damage and loss of mitochondrial membrane potential in target cancerous KB cells. Further, immunoblot analysis quantified the expression of caspases-3, -9 and poly(ADP-ribose) polymerase (PARP) also supports the cell damage. Thus, the findings of the study suggested that POL-PLGA-NPs effectively induced oxidative stress by initiating cellular damage leading to apoptosis in KB cells.

Liver histopathological alteration and dysfunction after bisphenol A administration in male rats and protective effects of naringin.

Objective:Bisphenol A (BPA) is an organic synthetic compound, often used in manufacturing polycarbonate plastics. Researches have shown the role of BPA as an endocrine disruptor. The present study intended to evaluate the hepatoprotective properties of naringin, an active flavanone glycoside present in many citrus fruit, against hepatotoxicity induced by BPA. Materials and Methods:Male Wistar rats were orally treated with 50 mg/kg BPA for 30 consecutive days for induction of toxicity and 40, 80 and 160 mg/kg naringin for the same period along with BPA or alone. Results:This study demonstrated that BPA significantly increased serum levels of triglyceride, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), lipid peroxidation, and aspartate aminotransferase (AST) and significantly reduced catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity, glutathione (GSH) and caused periportal inflammation and microvesicular steatosis in rat tissue. However, BPA did not change serum levels of high-density lipoprotein-cholesterol (HDL-C), total cholesterol, alanine aminotransferase (ALT), or low-density lipoprotein-cholesterol (LDL-C). Furthermore, the results displayed that administration of 80 and 160 mg/kg naringin improved hepatotoxicity and altered lipid peroxidation level, serum values of triglyceride and liver enzymes, and oxidative stress factors that were induced by BPA. The effect of two doses of 80 and 160 mg/kg naringin was more noticeable than that of dose 40 mg/kg. Conclusion:The findings suggested the protective effects of naringin against BPA-induced hepatotoxicity via ameliorating liver histopathological alteration, suppressing oxidative stress and lipid-lowering properties.

How the Pacific Oyster Responds to Ocean Acidification: Development and Application of a Meta-Analysis Based Adverse Outcome Pathway

Biological fitness relies on processes acting at various levels of organization, all of which can be modified by environmental change. Application of synthesis frameworks, such as the Adverse Outcome Pathway (AOP), can enhance our understanding of the responses to stressors identified in studies at each level, as well as the links among them. However, the use of such frameworks is often limited by a lack of data. In order to identify contexts with sufficient understanding to apply the AOP framework, we conducted a meta-analysis of studies considering ocean acidification effects on calcifying mollusks. Our meta-analysis identified that most studies considered the adult life history stage, bivalve taxonomic group, individual-level changes, as well as growth and metabolism related responses. Given the characteristics of published literature, we constructed an AOP for the effects of ocean acidification on calcification in an adult bivalve, specifically the Pacific oyster (Magallana gigas). By structuring results within the AOP framework we identify that, at present, the supported pathways by which ocean acidification affects oyster calcification are via the downregulation of cavortin and arginine kinase transcription. Such changes at the molecular level can prompt changes in cellular and organ responses, including altered enzyme activities, lipid peroxidation, and regulation of acid-base status, which have impacts on organism level metabolic rate and, therefore, calcification. Altered calcification may then impact organism mortality and population sizes. We propose that where developed and incorporated in future studies, the AOP framework could be used to investigate sources of complexity including varying susceptibility within and among species, feedback mechanisms, exposure duration and magnitude, and species interactions. Such applications of the AOP framework will allow more effective reflections of the consequences of environmental change, such as ocean acidification, on all levels of biological organization.

Protective effects of apigenin on altered lipid peroxidation, inflammation, and antioxidant factors in methotrexate-induced hepatotoxicity.

Methotrexate (MTX) is used as an effective chemotherapeutic agent against autoimmune diseases and tumors. Oxidative stress and inflammation are involved in the pathogenesis of MTX-induced damage. This study aimed at examining the ameliorating effects of apigenin (API) as a natural antioxidant on MTX-induced hepatotoxicity. The rats were classified into four groups: group I: normal saline-treated, group II: MTX-treated (20 mg/kg, ip, single dose at day 7), group III: MTX + API-treated (20 mg/kg, po), and group IV: API-treated. API was administrated for 9 days. Alanine aminotransferase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) were used as biochemical factors of MTX-induced hepatic injury. In hepatic tissues, the levels of malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), and activities of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) as oxidative stress markers along with inflammatory factors such as tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1β) were assessed. Our results showed that MTX administration significantly increased ALP, ASP, ALT, MDA, NO, TNF-α, and IL-1β levels and significantly decreased antioxidant factors such as GSH, CAT, GPx, and SOD. The API pretreatment group showed a significant rise in hepatic antioxidant markers, besides significant reductions in the serum levels of AST, ALT, and ALP and hepatic content of MDA, TNF-α, NO, and IL-1β. In addition, the hepatoprotective effect of API was confirmed by histological evaluation of the liver. API can prevent MTX-induced hepatotoxicity through mitigation of oxidative stress and inflammation.

Beauvericin and ochratoxin A mycotoxins individually and combined in HepG2 cells alter lipid peroxidation, levels of reactive oxygen species and glutathione

The co-presence of more than one mycotoxin in food is being evidenced in last food surveys as reported in the literature. Beauvericin (BEA) is a non-legislated emergent mycotoxin while Ochratoxin A (OTA) has been widely studied and legislated. Concentration range individually studied was from 2.5 to 0.3 μM for BEA and from 25 to 3.1 μM for OTA; binary mixture [BEA + OTA] comprised concentrations of 1:10 ratio from [2.5 + 25] to [3.1 + 0.3] μM. Potential of toxicity of BEA in HepG2 cells was the highest at all times assayed (24, 48 and 72h). LPO was performed through malondyaldehyde (MDA) detection denoting in the binary mixture for [1.25 + 12.5] μM and at 24 and 72h the highest disturbance values. ROS denoted differences respect to the control at different times specially for OTA, while in binary combination only for few point times was denoted. Effects detected for ROS and LPO were connected with alterations detected for glutathione levels of oxidized and reduced form. A real scenario of consumers chronically exposed to different mycotoxins and their mixtures is here presented highlighting the good methodology to assess the risk from exposure to combinations of chemicals in food.

Exploring the Potential of Nitric Oxide and Hydrogen Sulfide (NOSH)-Releasing Synthetic Compounds as Novel Priming Agents against Drought Stress in Medicago sativa Plants.

Land plants are continuously exposed to multiple abiotic stress factors like drought, heat, and salinity. Nitric oxide (NO) and hydrogen sulfide (H2S) are two well-examined signaling molecules that act as priming agents, regulating the response of plants to stressful conditions. Several chemical donors exist that provide plants with NO and H2S separately. NOSH is a remarkable novel donor as it can donate NO and H2S simultaneously to plants, while NOSH-aspirin additionally provides the pharmaceutical molecule acetylsalicylic acid. The current study aimed to investigate the potential synergistic effect of these molecules in drought-stressed Medicago sativa L. plants by following a pharmacological approach. Plants were initially pre-treated with both donors (NOSH and NOSH-aspirin) via foliar spraying, and were then subsequently exposed to a moderate water deficit while NO and H2S inhibitors (cPTIO and HA, respectively) were also employed. Phenotypic and physiological data showed that pre-treatment with NOSH synthetic compounds induced acclimation to subsequent drought stress and improved the recovery following rewatering. This was accompanied by modified reactive-oxygen and nitrogen-species signaling and metabolism, as well as attenuation of cellular damage, as evidenced by altered lipid peroxidation and proline accumulation levels. Furthermore, real-time RT-qPCR analysis revealed the differential regulation of multiple defense-related transcripts, including antioxidant enzymes. Overall, the present study proposed a novel role for NOSH compounds as efficient plant priming agents against environmental constraints through the coordinated regulation of multiple defense components, thus opening new horizons in the field of chemical priming research toward the use of target-selected compounds for stress tolerance enhancement.

Bioefficacy of red cabbage against hypercholesterolemic diet mediated oxidative stress

BackgroundThe shift towards hypercaloric diets and sedentariness has raised lifestyle related disorders and escalated health care cost. In order to tackle this epidemiological transition, healthy, affordable food choices should be introduced in the routine menu. In this context, red cabbage is known for its rich phytochemistry, minerals, antioxidant vitamins and dietary fiber. Considering these evidences, red cabbage leaves and its extract were assessed against hypercholesterolemia and associated oxidative stress.MethodsIn bioefficacy assessment trial (12 weeks), there were two dietary regimens; normal and hypercholesterolemic (1% cholesterol) that were further split into three groups each. In both feeding trials, red cabbage leaves (20%) and its extract in dose equivalent to red cabbage leaves were assessed against control diets. At termination of trial, serum lipidemic parameters and oxidative stress biomarkers were assessed to test the efficacy of diets.ResultsIn hypercholesterolemic rabbits, red cabbage leaves showed significant reduction in cholesterol, LDL-c and triacylglycerol levels i.e. 15.19, 18.09 and 9.42% than extract administered groups; 10.79, 12.24 and 5.72, respectively. Besides, red cabbage leaves also portrayed momentous enhancement of superoxide dismutase (SOD) and catalase (CAT) activity up to 13.29 & 17.63% by lowering lipid peroxidation by 27.86% in hypercholesterolemic diet fed groups, whereas red cabbage extract administered group depicted relatively lesser amelioration in lipid peroxidation i.e. 21.42%.ConclusionsRed cabbage leaves possess higher ameliorative potential against altered lipidemic profile and lipid peroxidation as compared to its extract thus explains its ability to prevent exhaustion of endogenous antioxidant enzymes; SOD and CAT.

Monodehydroascorbate Reductase Plays a Role in the Tolerance of Chlamydomonas reinhardtii to Photooxidative Stress.

Monodehydroascorbate reductase (MDAR; EC 1.6.5.4) is one of the key enzymes in the conversion of oxidized ascorbate (AsA) back to reduced AsA in plants. This study investigated the role of MDAR in the tolerance of Chlamydomonas reinhardtii P.A. Dangeard to photooxidative stress by overexpression and downregulation of the CrMDAR1 gene. For overexpression of CrMDAR1 driven by a HSP70A:RBCS2 fusion promoter, the cells survived under very high-intensity light stress (VHL, 1,800 μmol�m-2�s-1), while the survival of CC-400 and vector only control (vector without insert) cells decreased for 1.5 h under VHL stress. VHL increased lipid peroxidation of CC-400 but did not alter lipid peroxidation in CrMDAR1 overexpression lines. Additionally, overexpression of CrMDAR1 showed an increase in viability, CrMDAR1 transcript abundance, enzyme activity and the AsA: dehydroascorbate (DHA) ratio. Next, MDAR was downregulated to examine the essential role of MDAR under high light condition (HL, 1,400 μmol�m-2�s-1). The CrMDAR1 knockdown amiRNA line exhibited a low MDAR transcript abundance and enzyme activity and the survival decreased under HL conditions. Additionally, HL illumination decreased CrMDAR1 transcript abundance, enzyme activity and AsA:DHA ratio of CrMDAR1-downregulation amiRNA lines. Methyl viologen (an O2�- generator), H2O2 and NaCl treatment could induce an increase in CrMDAR1 transcript level. It represents reactive oxygen species are one of the factor inducing CrMDAR1 gene expression. In conclusion, MDAR plays a role in the tolerance of Chlamydomonas cells to photooxidative stress.

Effect of ethanol and aqueous extracts of seed pod of Copaifera salikounda (Heckel) on complete Freund's adjuvant-induced rheumatoid arthritis in rats.

The antirheumatoid arthritis potential of ethanol and aqueous extracts of seed pod of Copaifera salikounda (SPCS) was evaluated using the chicken collagen/complete Freund's adjuvant-induced arthritic rats model. Adjuvat-induced rats were treated with varied doses of the extracts (400, 600, and 800mg/kg body weight) and with reference drug, indomethacin for 21days. Antiarthritic evaluation was done through measurement of body weight, paw size, inflammatory makers, hematological parameters, cytokines, antioxidant enzymes, reduced glutathione, lipid peroxidation as well as histopathological examinations. Treatment with the ethanol and aqueous extracts of SPCS markedly inhibited the paw size and caused weight gain. The extracts considerably modulated the hematological as well as the antioxidant parameters. Likewise, the extract restored the altered lipid peroxidation, pro-inflammatory mediators, and inflammatory factors which further accentuate the implication in adjuvant-induced arthritis. Thus, the ethanol and aqueous extracts of SPCS showed a significant antiarthritic activity that was statistically analogous to that of indomethacin. Practical applications Copaifera salikounda (Heckel) has been used in treatment of different ailments including rheumatoid arthritis in folklore medicine. This is the first reported proof of the antiarthritic potential of the seed pod. Oxidative stress has been implicated in rheumatoid arthritis. Ethanol extract of SPCS has been shown to be predominantly rich in phenols, terpenoids, alkaloids, and flavonoids which are natural antioxidant. The present study has demonstrated that ethanol and aqueous extracts of SPCS can exert antioxidative and antiinflammatory effects, thus strengthening its antiarthritic potentials.

Quercetin Potentiates Docosahexaenoic Acid to Suppress Lipopolysaccharide-induced Oxidative/Inflammatory Responses, Alter Lipid Peroxidation Products, and Enhance the Adaptive Stress Pathways in BV-2 Microglial Cells

High levels of docosahexaenoic acid (DHA) in the phospholipids of mammalian brain have generated increasing interest in the search for its role in regulating brain functions. Recent studies have provided evidence for enhanced protective effects when DHA is administered in combination with phytochemicals, such as quercetin. DHA and quercetin can individually suppress lipopolysaccharide (LPS)–induced oxidative/inflammatory responses and enhance the antioxidative stress pathway involving nuclear factor erythroid-2 related factor 2 (Nrf2). However, studies with BV-2 microglial cells indicated rather high concentrations of DHA (IC50 in the range of 60–80 µM) were needed to produce protective effects. To determine whether quercetin combined with DHA can lower the levels of DHA needed to produce protective effects in these cells is the goal for this study. Results showed that low concentrations of quercetin (2.5 µM), in combination with DHA (10 µM), could more effectively enhance the expression of Nrf2 and heme oxygenase 1 (HO-1), and suppress LPS–induced nitric oxide, tumor necrosis factor-α, phospho-cytosolic phospholipase A2, reactive oxygen species, and 4-hydroxynonenal, as compared to the same levels of DHA or quercetin alone. These results provide evidence for the beneficial effects of quercetin in combination with DHA, and further suggest their potential as nutraceuticals for improving health.