Involvement Of Lipid Peroxidation Research Articles

Investigating the role of the ROS/CncC-xenobiotics signaling pathway in the response to Fenpropathrin in Cyprinus carpio lymphocytes: Involving lipid peroxidation and Fe2+ metabolism imbalance

Fenpropathrin (FPT) is a synthetic pyrethroid insecticide, the persistence and accumulation in water of which could cause harmful effects on vulnerable groups like aquatic creatures, particularly posing significant risks to fish immune systems. This study aimed to investigate how environmentally relevant FPT concentrations (10–1000 μ/M) affect lipid peroxidation and Fe2+ metabolism in Cyprinus carpio head kidney lymphocytes, and its relationship with oxidative stress and immunotoxicity. Firstly, CCK-8 results demonstrated that FPT caused a significant increase in lymphocyte death. Secondly, lymphocytes exposed to FPT could lead ferroptosis in lymphocytes, accompanied by evidence of the Fe2+ transporter imbalance, lipid peroxidation, Fe2+ accumulation and ferroptosis related protein increment. Thirdly, we found that FPT esposure leads to a decrease in ATP, mitochondrial DNA and NADPH/NADP+ levels, and the mRNA associated with mitochondrial function-related genes (Fis1, Drp1, and OPA1) in lymphocytes. Additionally, FPT induced the increased the levels of inflammatory genes (TNF-α, IFN-γ, and IL-6) in head kidney lymphocytes. Importantly, exposure to FPT induced oxidative stress to produce intracellular ROS, disrupting the function of the CncC signaling pathway and expression disorder of xenobiotics detoxification (CYP 450 family) genes. Notably, Treatment with NAC (a ROS inhibitor, 5 μM) demonstrated that inhibiting ROS alleviated FPT-induced lymphocyte ferroptosis and inflammatory response via the ROS/CncC-xenobiotics signaling pathway. These findings not only introduces a novel approach to investigating the immunotoxicity of FPT but also offers critical insights into mitigating the adverse effects of FPT on aquatic animal health.

ANTIOXIDANT ENZYMES INVOLVED IN SEEDS’ GERMINATION MODULATED BY ACTIVE PRINCIPLES FROM PLANT EXTRACTS AND HYDROLYZED PROTEINS

Transition to organic farming requires the development of new methods to protect seeds from adverse factors. The germinative process and the post-germinative phase are strictly controlled by the oxidative balance involving lipid peroxidation, reactive oxygen species and enzymes activity, directing the plant viability and its further development. We focus our studies mainly on the seeds protection and fortification through natural solutions based on marigold and fenugreek extracts, steroid alkaloids from tomatoes and hydrolyzed proteins derived from leather waste industry. The structural configuration of the plant protection products proves significant effects fighting on different mechanisms of seeds’ oxidative stress. As well as the experimental design highlighted a tandem correlative mechanism between germination, decrease of lipid peroxidase and activation of catalase and superoxide-dismutase. SEM-PROTECT II was the most active biopesticide involved in these processes. Our findings directed complex research oriented to technological and experimental optimizations for the development of an innovative, efficient and competitive plant protection product to meet modern agriculture requirement.

Ferrous gluconate triggers ferroptosis in Escherichia coli: Implications of lipid peroxidation and DNA damage

Microbial ferroptosis has been proved to combat drug-resistant pathogens, but whether this pattern can be applied to the prevention and control of Escherichia coli remains to be further explored. In this study, ferrous gluconate (FeGlu) showed remarkable efficacy in killing E. coli MG1655 with a mortality rate exceeding 99.9%, as well as enterotoxigenic E. coli H10407 (ETEC H10407) and enterohemorrhagic E. coli O157:H7 (EHEC O157:H7). Bacteria death was instigated by the infiltration of Fe2+, accompanied by a burst of intracellular reactive oxygen species (ROS) and lipid peroxidation. Notably, mitigating lipid peroxidation failed to alleviate death of E. coli. Further findings confirmed that FeGlu induced DNA damage, and ΔrecA mutant showed more sensitive, implicating that DNA damage was involved in the death of E. coli. The direct interaction of Fe2+ with DNA was demonstrated by fluorescent staining, gel electrophoresis, and circular dichroism (CD). Moreover, proteomic analysis unveiled 50 differentially expressed proteins (DEPs), including 18 significantly down-regulated proteins and 32 significantly up-regulated proteins. Among them, the down-regulation of SOS-responsive transcriptional suppressor LexA indicated DNA damage induced severely by FeGlu. Furthermore, FeGlu influenced pathways such as fatty acid metabolism (FadB, FadE), iron-sulfur cluster assembly (IscA, IscU, YadR), iron binding, and DNA-binding transcription, along with α-linolenic acid metabolism, fatty acid degradation, and pyruvate metabolism. These pathways were related to FeGlu stress, including lipid peroxidation and DNA damage. In summary, FeGlu facilitated ferroptosis in E. coli through mechanisms involving lipid peroxidation and DNA damage, which presents a new strategy for the development of innovative antimicrobial strategies targeting E. coli infections.

Biodegradable and Efficient Charge-Migrated Z-Scheme Heterojunction Amplifies Cancer Ferroptosis by Blocking Defensive Redox System.

Ferroptosis is an emerging non-apoptotic death process, mainly involving lipid peroxidation (LPO) caused by iron accumulation, which is potentially lethal to the intrinsically apoptotic-resistant malignant tumor. However, it is still restricted by the inherent antioxidant systems of tumor cells and the poor efficacy of traditional iron-based ferroptosis initiators. Herein, the study develops a novel ferroptosis-inducing agent based on PEGylated Cu+/Cu2+-doped black phosphorus@polypyrrole heterojunction (BP@CPP), which is constructed by utilizing the phosphate on the surface of BP to chelate Cu ions and initiating subsequent in situ polymerization of pyrrole. As a novel Z-scheme heterojunction, BP@CPP possesses an excellent photocatalytic activity in which the separated electron-hole pairs under laser irradiation endow it with powerful oxidizing and reducing capacities, which synergy with Cu+/Cu2+ self-cycling catalyzing Fenton-like reaction to further strengthen reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, and glutathione peroxidase 4 (GPX4) inactivation, ultimately leading to efficient ferroptosis. Systematic in vitro and in vivo evaluations demonstrate that BP@CPP effectively inhibit tumor growth by inducing desired ferroptosis while maintaining a favorable biosafety in the body. Therefore, the developed BP@CPP-based ferroptosis initiator provides a promising strategy for ferroptosis-like cancer therapy.

Elevated extracellular inorganic phosphate inhibits ecto-phosphatase activity in breast cancer cells: Regulation by hydrogen peroxide.

For cells to obtain inorganic phosphate, ectoenzymes in the plasma membrane, which contain a catalytic site facing the extracellular environment, hydrolyze phosphorylated molecules. In this study, we show that increased Pi levels in the extracellular environment promote a decrease in ecto-phosphatase activity, which is associated with Pi-induced oxidative stress. High levels of Pi inhibit ecto-phosphatase because Pi generates H2 O2 . Ecto-phosphatase activity is inhibited by H2 O2 , and this inhibition is selective for phospho-tyrosine hydrolysis. Additionally, it is shown that the mechanism of inhibition of ecto-phosphatase activity involves lipid peroxidation. In addition, the inhibition of ecto-phosphatase activity by H2 O2 is irreversible. These findings have new implications for understanding ecto-phosphatase regulation in the tumor microenvironment. H2 O2 stimulated by high Pi inhibits ecto-phosphatase activity to prevent excessive accumulation of extracellular Pi, functioning as a regulatory mechanism of Pi variations in the tumor microenvironment.

Caveolae and the oxidative stress response.

Oxidative stress is a feature of many disease conditions. Oxidative stress can activate a number of cellular pathways leading to cell death, including a distinct iron-dependent pathway involving lipid peroxidation, termed ferroptosis, but cells have evolved complex mechanisms to respond to these stresses. Here, we briefly summarise current evidence linking caveolae to the cellular oxidative stress response. We discuss recent studies in cultured cells and in an in vivo model suggesting that lipid peroxidation driven by oxidative stress causes disassembly of caveolae to release caveola proteins into the cell where they regulate the master transcriptional redox controller, nuclear factor erythroid 2-related factor 2. These studies suggest that caveolae maintain cellular susceptibility to oxidative stress-induced cell death and suggest a crucial role in cellular homeostasis and the response to wounding.

Over-Expressed GATA-1S, the Short Isoform of the Hematopoietic Transcriptional Factor GATA-1, Inhibits Ferroptosis in K562 Myeloid Leukemia Cells by Preventing Lipid Peroxidation.

Ferroptosis is a recently recognized form of regulated cell death involving lipid peroxidation. Glutathione peroxidase 4 (GPX4) plays a central role in the regulation of ferroptosis through the suppression of lipid peroxidation generation. Connections have been reported between ferroptosis, lipid metabolism, cancer onset, and drug resistance. Recently, interest has grown in ferroptosis induction as a potential strategy to overcome drug resistance in hematological malignancies. GATA-1 is a key transcriptional factor controlling hematopoiesis-related gene expression. Two GATA-1 isoforms, the full-length protein (GATA-1FL) and a shorter isoform (GATA-1S), are described. A balanced GATA-1FL/GATA-1S ratio helps to control hematopoiesis, with GATA-1S overexpression being associated with hematological malignancies by promoting proliferation and survival pathways in hematopoietic precursors. Recently, optical techniques allowed us to highlight different lipid profiles associated with the expression of GATA-1 isoforms, thus raising the hypothesis that ferroptosis-regulated processes could be involved. Lipidomic and functional analysis were conducted to elucidate these mechanisms. Studies on lipid peroxidation production, cell viability, cell death, and gene expression were used to evaluate the impact of GPX4 inhibition. Here, we provide the first evidence that over-expressed GATA-1S prevents K562 myeloid leukemia cells from lipid peroxidation-induced ferroptosis. Targeting ferroptosis is a promising strategy to overcome chemoresistance. Therefore, our results could provide novel potential therapeutic approaches and targets to overcome drug resistance in hematological malignancies.

ACSL3 regulates lipid droplet biogenesis and ferroptosis sensitivity in clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC), the predominant subtype of kidney cancer, possesses characteristic alterations to multiple metabolic pathways, including the accumulation of cytosolic lipid droplets. However, the pathways that drive lipid droplet accumulation in ccRCC cells and their importance to cancer biology remain poorly understood.MethodsWe sought to identify the carbon sources necessary for lipid droplet accumulation using Oil red O staining and isotope-tracing lipidomics. The role of the acyl-CoA synthetase (ACSL) family members, an important group of lipid metabolic enzymes, was investigated using siRNA and drug mediated inhibition. CTB and XTT assays were performed to determine the effect of ACSL3 knockdown and lipid starvation on ccRCC cell viability and shRNA was used to study the effect of ACSL3 in an orthotopic mouse model. The relationship between ferroptosis susceptibility of ccRCC and ACSL3 controlled lipid metabolism was examined using CTB and FACS-based assays. The importance of 5-LOX in ferroptosis susceptibility in ccRCC was shown with XTT survival assays, and the expression level and predictive value of 5-LOX in TCGA ccRCC data was assessed.ResultsWe found that ccRCC cells obtain the necessary substrates for lipid droplet accumulation by metabolizing exogenous serum derived lipids and not through de novo lipogenesis. We show that this metabolism of exogenous fatty acids into lipid droplets requires the enzyme acyl-CoA synthetase 3 (ACSL3) and not other ACSL family proteins. Importantly, genetic or pharmacologic suppression of ACSL3 is cytotoxic to ccRCC cells in vitro and causes a reduction of tumor weight in an orthotopic mouse model. Conversely, ACSL3 inhibition decreases the susceptibility of ccRCC cells to ferroptosis, a non-apoptotic form of cell death involving lipid peroxidation. The sensitivity of ccRCC to ferroptosis is also highly dependent on the composition of exogenous fatty acids and on 5-lipoxygenase (5-LOX), a leukotriene producing enzyme which produces lipid peroxides that have been implicated in other cancers but not in ccRCC.ConclusionsACSL3 regulates the accumulation of lipid droplets in ccRCC and is essential for tumor growth. In addition, ACSL3 also modulates ferroptosis sensitivity in a manner dependent on the composition of exogenous fatty acids. Both functions of ACSL3 could be exploited for ccRCC therapy.

Excess DHA Induces Liver Injury via Lipid Peroxidation and Gut Microbiota-Derived Lipopolysaccharide in Zebrafish.

Being highly unsaturated, n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) are prone to lipid peroxidation. In this study, zebrafish were fed with low-fat diet (LFD), high-fat diet (HFD), or 2% DHA-supplemented HFD (HFDHA2.0). To study the possible negative effects of the high level of dietary DHA, growth rates, blood chemistry, liver histology, hepatic oxidative stress, apoptosis, and inflammatory processes were assessed. The cell studies were used to quantify the effects of DHA and antioxidant on cellular lipid peroxidation and viability. The possible interaction between gut microbiota and zebrafish host was evaluated in vitro. HFDHA2.0 had no effect on hepatic lipid level but induced liver injury, oxidative stress, and hepatocellular apoptosis, including intrinsic and death receptor-induced apoptosis. Besides, the inclusion of 2% DHA in HFD increased the abundance of Proteobacteria in gut microbiota and serum endotoxin level. In the zebrafish liver cell model, DHA activated intrinsic apoptosis while the antioxidant 4-hydroxy-Tempo (tempo) inhibited the pro-apoptotic negative effects of DHA. The apoptosis induced by lipopolysaccharide (LPS) was unaffected by the addition of tempo. In conclusion, the excess DHA supplementation generates hepatocellular apoptosis-related injury to the liver. The processes might propagate along at least two routes, involving lipid peroxidation and gut microbiota-generated LPS.

Plasma levels of oxysterols 7-ketocholesterol and cholestane-3β, 5α, 6β-triol in patients with allergic asthma

Objective: The prevalence of allergic asthma is increasing on a global scale, reflecting changes in air pollution, climatic changes, and other environmental stimulants. In allergic conditions, oxidative stress occurs as a result of immune system activation. Oxidation of cholesterol leads to the formation of oxysterols. The main purpose of the study was to compare plasma levels of two oxysterols, namely 7-ketocholesterol (7-KC) and cholestane-3β, 5α, 6β-triol (C-triol), and a lipid peroxidation product, malondialdehyde (MDA) in allergic asthma patients with those of healthy controls, in order to provide information about the involvement of lipid peroxidation in allergic asthma. Methods: Oxysterols were quantified by LC-MS/MS in plasma samples of 120 asthma patients (90 females + 30 males) and 120 healthy controls (matched by age and sex). Plasma MDA level was analyzed by a spectrophotometric method. Results: Plasma 7-KC (39.45 ± 20.37 ng/mL) and C-triol (25.61 ± 10.13 ng/mL) levels in patients were significantly higher than in healthy subjects (17.84 ± 4.26 ng/mL and 10.00 ± 3.90 ng/mL, respectively) (P < 0.001). Plasma MDA levels were also higher in asthmatic patients (4.98 ± 1.77 nmol/mL) than in healthy controls (1.14 ± 0.31 nmol/mL) (P < 0.001). All data support that lipid peroxidation products are involved in allergic asthma. Conclusion: Oxysterols were quantified for the first time in allergic asthma. Since the high plasma 7-KC and C-triol levels of allergic asthma patients correlate with high IgE levels, detection of these oxysterols by LC-MS/MS may be helpful in the clinical monitoring of allergic asthma. Current data may also lead to new approaches for the prevention, diagnosis, and treatment of the disease. Supplemental data for this article is available online at at.

Oxidized Low-Density Lipoproteins increases nivolumab-induced cardiotoxicity through TLR4/NF-KB and NLRP3 pathways

Abstract Background Atherosclerosis is now recognized as a chronic inflammatory disease. Oxidized low-density lipoprotein (Ox-LDL) is oxidatively modified form of LDL with a key role in induction and progressio of atherosclerosis. Recent findings reported that cardiovascular events (myocarditis and atherosclerosis) were higher after initiation of immune check-point inhibitors (ICIs), potentially mediated by accelerated progression of atherosclerosis. Purpose We evaluated whether ox-LDL-induced apoptosis through toll-like receptor-4 (TLR4)/Nuclear factor κB (NF-κB) signaling pathway and NLRP3 inflammasome during exposure of human cardiomyocytes to nivolumab turning the light on the mechanisms of cell inflammation induced by OxLDL in cardiotoxicity of ICIs. Methods Human fetal cardiomyocytes (HFC cell line) in co-culture with hPBMC, were exposed to clinically relevant concentration of nivolumab (100 nM) alone or combined to OxLDL at 1, 10 and 50 μg/mL for 24h. After the incubation period, we performed the following tests: determination of cell viability, through analysis of mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular Malondialdehyde and 4-hydroxynonenal), intracellular Ca2+ homeostasis and apoptosis. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome, expression of TLR4 and NF-kB). In order to evaluate the pathways involved in OxLDL damages, TLR4 and NLRP3 inhibitor (TAK-242 and dapansutrile, respectively) were added during cell viability and apoptosis studies. Results Nivolumab exerts cytotoxic and pro-apoptotic effects in co-coltures of cardiomyocytes and hPBMC. OxLDL increases significantly the nivolumab-induced cardiotoxicity in a manner that is sensitive to TLR4 and NLRP3. Incubation of cardiomyocytes with ox-LDL (10 and 50 μg/mL) for 24 hours increased TLR4 and NF-κB expressions. Ox-LDL had pro-apoptotic effects in a concentration-dependent manner with the involvement of lipid peroxidation but not of intracellular calcium. Conclusion Ox-LDL exacerbates cardiotoxicity during exposure to nivolumab through pro-inflammatory mechanisms. These results place the first step to preclinical studies aimed to reduce ox-LDL during treatment with ICIs through pharmacological inhibition or by changing diet and lifestyle. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministero della Salute, Ricerca Corrente project

Exposure Impacts of Diquat dibromide herbicide formulation on amphibian larval development

Many anthropogenic chemicals in general, and specifically aquatic herbicide formulations have the potential to modulate the thyroid pathways of the endocrine system of aquatic organisms, because they are normally applied directly into the aquatic system, to manage aquatic weeds. These thyroidal effects have been widely linked with disruption in developmental and reproductive processes. In fact, the exposure impacts of many of these substances on metamorphic organisms could produce a precocious metamorphosis. Using Xenopus Metamorphosis Assay (XEMA) protocol, this study assessed the thyroidal effects of environmentally relevant concentrations of Diquat dibromide at 0.05, 0.11, and 0.14 mg/L on Xenopus laevis metamorphosis. The formulation significantly reduced both the fore and hind limb lengths, and disrupted the developmental stage at concentrations of 0.11 and 0.14 mg/L, with a median at NF-stage 57, while median of NF-stage 60 was recorded in the control. Histopathologically, although there was no significant difference in thyroid gland area, the thyroid colloidal area was significantly reduced at 0.14 mg/L, while the mean height of the thyroid follicle increased at 0.05 mg/L The result indicates an extra-thyroidal pathway, due to the dissociation between stage developmental effects and thyroid histopathology. The role of stress pathway occasioned by oxidative mode of action, involving lipid peroxidation and cell damage observed in this study need further investigation, in order to further characterize the physiological and ecological effects on wildlife.

Ferrotoxicity and Its Amelioration by Calcitriol in Cultured Renal Cells.

Globally, acute kidney injury (AKI) is associated with significant mortality and an enormous economic burden. Whereas iron is essential for metabolically active renal cells, it has the potential to cause renal cytotoxicity by promoting Fenton chemistry-based oxidative stress involving lipid peroxidation. In addition, 1,25-dihydroxyvitamin D3 (calcitriol), the active form of vitamin D, is reported to have an antioxidative role. In this study, we intended to demonstrate the impact of vitamin D on iron-mediated oxidant stress and cytotoxicity of Vero cells exposed to iohexol, a low osmolar iodine-containing contrast media in vitro. Cultured Vero cells were pretreated with 1,25-dihydroxyvitamin D3 dissolved in absolute ethanol (0.05%, 2.0 mM) at a dose of 1 mM for 6 hours. Subsequently, iohexol was added at a concentration of 100 mg iodine per mL and incubated for 3 hours. Total cellular iron content was analysed by a flame atomic absorption spectrophotometer at 372 nm. Lipid peroxidation was determined by TBARS (thiobarbituric acid reactive species) assay. Antioxidants including total thiol content were assessed by Ellman's method, catalase by colorimetric method, and superoxide dismutase (SOD) by nitroblue tetrazolium assay. The cells were stained with DAPI (4′,6-diamidino-2-phenylindole), and the cytotoxicity was evaluated by viability assay (MTT assay). The results indicated that iohexol exposure caused a significant increase of the total iron content in Vero cells. A concomitant increase of lipid peroxidation and decrease of total thiol protein levels, catalase, and superoxide dismutase activity were observed along with decreased cell viability in comparison with the controls. Furthermore, these changes were significantly reversed when the cells were pretreated with vitamin D prior to incubation with iohexol. Our findings of this in vitro model of iohexol-induced renotoxicity lend further support to the nephrotoxic potential of iron and underpin the possible clinical utility of vitamin D for the treatment and prevention of AKI.

Genome-Wide Association Study Dissects the Genetic Architecture of Maize Husk Tightness.

The husk is a leafy outer tissue that encloses a maize ear. Previously, we identified the optimum husk structure by measuring the husk length, husk layer number, husk thickness and husk width. Husk tightness (HTI) is a combined trait based on the above four husk measurements. Unveiling the genetic basis of HTI will aid in guiding the genetic improvement of maize for mechanical harvesting and for protecting the ear from pest damage and pathogen infection. Here, we used a maize associate population of 508 inbred lines with tropical, subtropical and temperate backgrounds to analyze the genetic architecture of HTI. Evaluating the phenotypic diversity in three different environments showed that HTI exhibited broad natural variations and a moderate heritability level of 0.41. A diversity analysis indicated that the inbred lines having a temperate background were more loosely related than those having a tropical or subtropical background. HTI showed significant negative correlations with husk thickness and width, which indicates that thicker and wider husks wrapped the ear tighter than thinner and slimmer husks. Combining husk traits with ∼1.25 million single nucleotide polymorphisms in a genome-wide association study revealed 27 variants that were significantly associated with HTI above the threshold of P < 7.26 × 10–6. We found 27 candidate genes for HTI that may participate in (1) husk senescence involving lipid peroxidation (GRMZM2G017616) and programmed cell death (GRMZM2G168898 and GRMZM2G035045); (2) husk morphogenesis involving cell division (GRMZM5G869246) and cell wall architecture (GRMZM2G319798); and (3) cell signal transduction involving protein phosphorylation (GRMZM2G149277 and GRMZM2G004207) and the ABSISIC ACID INSENSITIVE3/VIVIPAROUS1 transcription factor (GRMZM2G088427). These results provide useful information for understanding the genetic basis of husk development. Further studies of identified candidate genes will help elucidate the molecular pathways that regulate HTI in maize.

Age-related changes of the human retinal vessels: Possible involvement of lipid peroxidation

BackgroundAging of the human retina is accompanied by oxidative stress that exerts profound changes in the retinal neurons. It is unknown if oxidative stress influences the cellular components of the retinal vessels in some ways. MethodsWe examined changes in retinal vessels in human donor eyes (age: 35–94 years; N=18) by light and transmission electron microscopy, TUNEL and immunohistochemistry for biomarkers of vascular smooth muscle cells (SMC; actin), oxidative stress (4-hydroxy 2-nonenal [HNE] and nitrotyrosine), microglia (Iba-1) and vessels (isolectin B4). ResultsThe earliest changes in the endothelium and pericytes of capillaries are apparent from the seventh decade. With aging, there is clear loss of organelles and cytoplasmic filaments, and a progressive thickening of the endothelial and pericyte basal lamina. Loss of filaments, accumulation of lipofuscin and autophagic vacuoles are significant events in aging pericytes and SMC. Actin immunolabelling reveals discontinuity in arterial SMC layers during eighth decade, indicating partial degeneration of SMC. This is followed by hyalinization, with degeneration of the endothelium and SMC in arteries and arterioles of the nerve fibre layer (NFL) and ganglion cell layer in ninth decade. Iba-1 positive microglia were in close contact with the damaged vessels in inner retina, and their cytoplasm was rich in lysosomes. HNE immunoreactivity, but not of nitrotyrosine, was detected in aged vessels from seventh decade onwards, suggesting that lipid peroxidation is a major problem of aged vessels. However, TUNEL positivity seen during this period was limited to few arteries and venules of NFL. ConclusionThis study shows prominent age-related alterations of the pericytes and SMC of retinal vessels. These changes may limit the energy supply to the neurons and be responsible for age-related loss of neurons of the inner retina.

English

There are many reports which show a positive relationship between free radical damage and diseases such as cancer. Free radicals are formed when humans are exposed to ionizing radiation or during oxidation process in human beings can damage tissues and may potentially lead to development of cancers. Since radiation may be used in the management of cancer, there is need for the development of a radioprotective herbal medicine that can be used to increase the therapeutic index of radiotherapy and chemotherapy treatments by offering protection to non cancerous cells. Since most fruits contain polyphenols, they are radical scavengers which can effectively prevent cancer development due to increased reactive oxygen species. The aim of this research was to evaluate how fruit extracts of Annona stenophylla diels and Flacourtia indica may help in the prevention of cancer using UV light induced red blood cell (RBC) haemolysis and1, 1-diphenyl-2-picrylhydrazyl (DPPH) assays. Since cancer pathogenesis may involve lipid peroxidation, UV induced haemolysis and DPPH assays were used to examine the role of the fruit extracts in radioprotection and free radical quenching in order to prevent peroxidation. Phenolic compounds were extracted using aqueous methanol and the two assays were carried out using concentrations ranging from 20 to 200 µg/ml. The results were analysed using T test. The fruit extracts from the two plants showed a marked antioxidant and radioprotection efficacy against lipid peroxidation in the presence of UV light. Both assays showed a significant absorbance inhibition at (p < 0.05) implying that the fruit extracts were effective radical scavengers and radioprotectors. The results obtained suggest that the fruit extracts were good plasma membrane stabilizers and good radical quenchers. The membrane of red blood cells was stabilized by preventing UV induced peroxidation, a process in which free radicals are formed. These findings suggests that fruit extracts obtained from A. stenophylla diels and F.indica plants can be incorporated in pharmaceuticals formulations as nutraceuticals for prevention cancer and improvement of radiotherapy and chemotherapy therapeutic index. Key words: DPPH, radioprotective, cancer, UV visble, A. stenophylla diels, F.indica, reactive oxygen species.

Amelorative effects of anethum graveolens (Dill) against lornoxicam toxicity in rats

Lornoxicam (LOR) is a non-steroidal anti-inflammatory drug known to induce hepato-renal toxicity. The following study aimed to investigate the adverse effect of LOR in oxidative status beside biochemical and histological examination of Liver and kidney tissue as well as the protective effect ofDill. Thirty six male Wister albino rats were randomly divided into main four groups of nine rats each were used; G(1)Control group and they were administered 0.5ml of saline orally for 21 consecutive days, G (2):they were administered 2g/kg dill orally for 21consecutive days, G (3): they were administered 1.3 mg/kg body weight/day of LORintraperitonially for 21 consecutive days, G (4): they were administered 2g/kg dill orally concurrently with 1.3 mg/kg body weight/day of LOR. The results revealed that LOR induced significant increases in liver and kidney function parameters including AST, ALT, creatinine, and urea. Disrupted lipid metabolism also was observed in LOR-treated animals. Moreover, marked an increase in malondialdehyde (MDA) and decreases in glutathione (GSH) and catalase (CAT) following LOR-insult suggested a possible involvement of lipid peroxidation in LOR-induced hepatorenal toxicity.Oral administration of dill at the dose 2g/kg for 21 days was significantly mitigating these toxic effects.So it is concluded that dill has great hepatorenal, antioxidant and antiopoptotic effect.

Long chain lipid hydroperoxides increase the glutathione redox potential through glutathione peroxidase 4

BackgroundPeroxidation of PUFAs by a variety of endogenous and xenobiotic electrophiles is a recognized pathophysiological process that can lead to adverse health effects. Although secondary products generated from peroxidized PUFAs have been relatively well studied, the role of primary lipid hydroperoxides in mediating early intracellular oxidative events is not well understood. MethodsLive cell imaging was used to monitor changes in glutathione (GSH) oxidation in HAEC expressing the fluorogenic sensor roGFP during exposure to 9-hydroperoxy-10E,12Z-octadecadienoic acid (9-HpODE), a biologically important long chain lipid hydroperoxide, and its secondary product 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE). The role of hydrogen peroxide (H2O2) was examined by direct measurement and through catalase interventions. shRNA-mediated knockdown of glutathione peroxidase 4 (GPx4) was utilized to determine its involvement in the relay through which 9-HpODE initiates the oxidation of GSH. ResultsExposure to 9-HpODE caused a dose-dependent increase in GSH oxidation in HAEC that was independent of intracellular or extracellular H2O2 production and was exacerbated by NADPH depletion. GPx4 was involved in the initiation of GSH oxidation in HAEC by 9-HpODE, but not that induced by exposure to H2O2 or the low molecular weight alkyl tert-butyl hydroperoxide (TBH). ConclusionsLong chain lipid hydroperoxides can directly alter cytosolic EGSH independent of secondary lipid oxidation products or H2O2 production. NADPH has a protective role against 9-HpODE induced EGSH changes. GPx4 is involved specifically in the reduction of long-chain lipid hydroperoxides, leading to GSH oxidation. SignificanceThese results reveal a previously unrecognized consequence of lipid peroxidation, which may provide insight into disease states involving lipid peroxidation in their pathogenesis.

Taurine Supplementation Ameliorates Arsenic-Induced Hepatotoxicity and Oxidative Stress in Mouse.

We previously reported that taurine treatment inhibited arsenic (As)-induced apoptosis in the liver of mice. This study was designed to explore the effect of taurine on liver function and its underlying mechanism in As-exposed mice. Mice were randomly divided into 3 groups, ten mice in each group. Group 1, control group, only orally received drinking water alone. Group 2, As intoxication group, was exposed to 4mg/L As2O3 via drinking water for 60days. Group 3, taurine protection group, was treated with 4mg/L As2O3 and 150mg/kg both. Taurine administration significantly revered the increases of alanine transaminase (ALT) and aspartate transaminase (AST) activities in serum. The decrease of glutathione (GSH) was inhibited with taurine treatment in the liver of As-exposed mice. At the same time, taurine significantly inhihibited As-induced enhancement of malondialdehyde (MDA) in the liver. Here we show that taurine protective effect on liver function in As-exposed mice maybe involve lipid peroxidation.

Salivary antioxidant enzymes and lipid peroxidation product malondialdehyde and sialic acid levels among smokers and non-smokers with chronic periodontitis-A clinico-biochemical study.

Background:Pathogenesis of most of the inflammatory process are associated with reactive oxygen species (ROS), derived from various metabolic sources and which may lead to direct or indirect tissue damage due to oxidative stress, resulting in periodontal diseases. Usually antioxidant systems are capable of removing free radicals, thereby preventing tissue damage from free radical. ROS can result in tissue damage, involving lipid peroxidation. The aim of this study was to evaluate and compare the levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), and sialic acid (SA) in periodontally healthy and chronic periodontitis among nonsmokers and smokers and to determine their value as diagnostic markers for chronic periodontitis.Materials and Methods:A total of 90 male patients aged 20--60 years were recruited and grouped as Group 1: 30 Healthy nonsmokers, who had never smoked. Group 2: 30 nonsmokers with chronic periodontitis. Group 3: 30 smokers with chronic periodontitis. Unstimulated saliva was collected for at least 5 min and clinical measurements; SOD, GPx, MDA and SA were assessed using a spectrophotometric method.Results:Data showed a significant correlation between salivary SOD, GPx, MDA, and SA in group 1, group 2, and group 3. SOD and GPx were found to be lower and MDA and SA levels were found to be higher among smokers with chronic periodontitis.Conclusion:Reduced levels of antioxidant enzymes SOD and GPx and elevated levels of lipid peroxidation product MDA as well as increased levels of SA could be used as diagnostic markers to measure oxidative stress in periodontal disease associated with risk factor such as smoking.