End Product Of Lipid Peroxidation Research Articles

Utilizing Iron for Targeted Lipid Peroxidation as Anticancer Option of Integrative Biomedicine: A Short Review of Nanosystems Containing Iron.

Traditional concepts of life sciences consider oxidative stress as a fundamental process of aging and various diseases including cancer, whereas traditional medicine recommends dietary intake of iron to support physiological functions of the organism. However, due to its strong pro-oxidative capacity, if not controlled well, iron can trigger harmful oxidative stress manifested eventually by toxic chain reactions of lipid peroxidation. Such effects of iron are considered to be major disadvantages of uncontrolled iron usage, although ferroptosis seems to be an important defense mechanism attenuating cancer development. Therefore, a variety of iron-containing nanoparticles were developed for experimental radio-, chemo-, and photodynamic as well as magnetic dynamic nanosystems that alter redox homeostasis in cancer cells. Moreover, studies carried over recent decades have revealed that even the end products of lipid peroxidation, represented by 4-hydroxynonenal (4-HNE), could have desirable effects even acting as kinds of selective anticancer substances produced by non-malignant cells for defense again invading cancer. Therefore, advanced nanotechnologies should be developed for using iron to trigger targeted lipid peroxidation as an anticancer option of integrative biomedicine.

Evaluation of Salivary Lipid Peroxidation End Product Level in Dental Caries

Tissue destruction can be measured by the level of lipid peroxidation (LP) end products. Since free radicals are very reactive with low survival time, the level of free radicals and oxidative stress activity are measured indirectly by tissue damage end product assessment, i.e. Malondialdehyde (MDA) that is a final end product of LP. The aim of this study was to evaluate salivary MDA level as an indicator of oxidative stress; in caries-active and caries-free students. A total of 100 male and female students, 15-17 years of age, participated in this casecontrol study. Five mL of whole saliva was obtained. Salivary MDA level was measured spectrophotometrically. Statistical comparisons were performed with Student's t-test, using SPSS 13. Salivary MDA level was significantly higher in the caries-active group compared to the control caries-free group. MDA was also slightly lower in males. Higher MDA level might indicate caries-induced oxidative stress. In this study there was a relationship between salivary MDA level and dental caries. Therefore oxidative stress suppression might prevent caries initiation and progression.

Effects of Gsta4 deficiency on age-related cochlear pathology and hearing loss in mice.

The glutathione transferase (GST) detoxification system converts exogenous and endogenous toxins into a less toxic form by conjugating the toxic compound to reduced glutathione (GSH) by a variety of GST enzymes. Of the ~20 GST isoforms, GSTA4 exhibits high catalytic efficiency toward 4-hydroxynonenal (4-HNE), one of the most abundant end products of lipid peroxidation that contributes to neurodegenerative diseases and age-related disorders. Conjugation to GSH by GSTA4 is thought to be a major route of 4-HNE elimination. In the current study, we investigated the effects of Gsta4 deficiency on age-related cochlear pathology and hearing loss using young (3-5months old) and old (24-25months old) Gsta4+/+ and Gsta4-/- mice that were backcrossed onto the CBA/CaJ mouse strain, a well-established model of age-related hearing loss (AHL). At 3-5months of age, loss of Gsta4 resulted in decreased total GSTA activity toward 4-HNE in the inner ears of young mice. However, there were no differences in the levels of 4-HNE in the inner ears between Gsta4+/+ and Gsta4-/- mice at 3-5 or 24-25months of age. No histological abnormalities were observed in the cochlea and no hearing impairments were observed in young Gsta4-/- mice. At 24-25months of age, both Gsta4+/+ and Gsta4-/- mice showed elevated ABR thresholds compared to 3-month-old mice, but there were no differences in ABR thresholds, cochlear spiral ganglion neuron densities, or stria vascularis thickness between Gsta4+/+ and Gsta4-/- mice. Together, these results suggest that under normal physiological conditions or during normal aging, GSTA4 is not essential for removal of 4-HNE in mouse inner ears.

Oral supplementation of the Extract of Fish oil to reduce fasting blood Glucose and Endothel damage but not Malondialdehyde level in diabetic male Wistar Rat (Rattus norvegicus)

The main target of hyperglycaemia is endothelial dysfunction involving pathways; protein kinase activation, hexosamine activation, polyol activation, and Advanced Glycation End Products (AGEs) formation, trigger reactive radical superoxide (O2•-) to stress oxidative. Malondialdehyde (MDA) is an end product of lipid peroxidation in body and is an indicator of oxidant-antioxidant level in diabetic patients. Fish oil composing mostly omega 3 as an antioxidant can reduce oxidative stress and hyperglycaemic condition. This study aimed to investigated the effects of omega-3-rich fish oil in lowering blood sugar levels, inhibiting oxidative stress and aortic endothelial cell damage in diabetic rat models. This study was an experimental study using post-test only control group design. Thirty-two rats divided into two study groups (n = 16 individuals per group), including the diabetic rat’s group (as control) and the diabetic rats group given fish oil doses of 300 mg/kilogram body weight/day. Provision of fish oil was performed for 28 days used Blackmores® fish oil. Blood sugar and malondialdehyde levels were analyzed by spectrophotometric method. The number of aortic endothelial cells was analyzed by haematoxylin-eosin staining. Comparability test showed that the average number of fasting blood glucose level after treatment in both groups showed highly significant differences (p=0.00). Although MDA level was reduced in treatment group than control group, but statistically not significantly difference, p=0.43. Comparability test showed that average of endothelial cell between control and treatment group significantly different (p=0.00). It was concluded that fish oil supplementation containing omega-3 in diabetic rats can lower blood glucose level and can inhibit endothelial cell damage.

Can Medicinal Plants and Bioactive Compounds Combat Lipid Peroxidation Product 4-HNE-Induced Deleterious Effects?

The toxic reactive aldehyde 4-hydroxynonenal (4-HNE) belongs to the advanced lipid peroxidation end products. Accumulation of 4-HNE and formation of 4-HNE adducts induced by redox imbalance participate in several cytotoxic processes, which contribute to the pathogenesis and progression of oxidative stress-related human disorders. Medicinal plants and bioactive natural compounds are suggested to be attractive sources of potential agents to mitigate oxidative stress, but little is known about the therapeutic potentials especially on combating 4-HNE-induced deleterious effects. Of note, some investigations clarify the attenuation of medicinal plants and bioactive compounds on 4-HNE-induced disturbances, but strong evidence is needed that these plants and compounds serve as potent agents in the prevention and treatment of disorders driven by 4-HNE. Therefore, this review highlights the pharmacological basis of these medicinal plants and bioactive compounds to combat 4-HNE-induced deleterious effects in oxidative stress-related disorders, such as neurotoxicity and neurological disorder, eye damage, cardiovascular injury, liver injury, and energy metabolism disorder. In addition, this review briefly discusses with special attention to the strategies for developing potential therapies by future applications of these medicinal plants and bioactive compounds, which will help biological and pharmacological scientists to explore the new vistas of medicinal plants in combating 4-HNE-induced deleterious effects.

Oxidative stress in seminal plasma and its relation to fertility potential of human male subjects

Background: There is growing evidence that damage to spermatozoa by reactive oxygen species (ROS) plays a key role in male infertility. Human spermatozoa are susceptible to ROS as their plasma membrane contains abundant polyunsaturated fatty acid which can undergo lipid peroxidation which may cause damage to the sperms. Lipid peroxidation of sperm membrane is an important mechanism of this ROS-induced sperm damage leading to infertility. The present study was undertaken using malondialdehyde (MDA) for assessing oxidative stress which is an end product of lipid peroxidation. Aim and Objectives: The aim of this study was to evaluate the oxidative stress by estimating MDA (marker of lipid peroxidation) in seminal plasma of different groups of individuals and to correlate the levels with different seminogram parameters. Materials and Methods: Semen samples were obtained and analyzed for routine seminogram parameters from 150 male partners between ages 20 and 58 years of infertile couples attending reproductive biology unit. The patients were grouped into abnormal ejaculate (asthenoteratozoospermic ORIGINAL ARTICLE, oligoasthenoteratozoospermic, and azoospermic) and normal ejaculate groups. Oxidative stress was measured spectrophotometrically by estimating MDA. Results: Higher MDA levels of seminal plasma were observed in the AT and azoospermic groups as compared to normozoospermics though the difference was not statistically different. A significant rise in MDA levels was observed in the oligoasthenoteratozoospermic group. Seminogram parameters were found to be negatively correlated with seminal MDA level. Conclusion: Increased seminal plasma lipid peroxidation is likely to have an association with poor semen quality. Hence, MDA may be used as one of the biomarkers for assessing oxidative stress on sperm.

The effect of Roundup on the bivalve Unio tumidus mollusk utilizing ex vivo approach

Glyphosate is the worldwide used herbicide of the first priority. However, its biochemical effects in the aquatic animals are studied scantly. The ex vivo approach has been recently proposed to provide the express evaluation of the adverse impact without the treating of the organisms. The aim of this study was to verify this approach for the assessment of the toxicity of glyphosate to the bivalve mollusk. The samples of the gills and digestive gland tissues of freshwater bivalve Unio tumidus mollusk were exposed to a range of the concentrations of glyphosate (commercial formulation Roundup MAX) at the concentrations 13.3, 26.7, 66.8 and 133.6 µg×L -1 during 2 h at 20 °C followed by 15 h at ~ 2–4 o C. The markers of oxidative injury (total antioxidant activity, end-products of lipid peroxidation (TBARS) and protein carbonyls (PC)), cellular low weight thiols GSH/GSSG and metallothionein (MT), and cholinesterase activity as the index of neurotoxicity were analyzed. We also assayed the index of cell vitality as the lysosomal membrane stability from the Neutral Red Retention (NRR) test. The results have shown that the lowest concentrations of glyphosate caused the most prominent changes of the indices: the decrease of MT concentration (by ~ two times) and cholinesterase activity. The total antioxidant activity was decreased substantially in all exposures correspon­dingly to a decrease of the MT and/or GSH concentrations. However, the levels of TBARS and PC were not changed comparing to control detecting the early stage of the injury. Surprisingly, NRR increased in the exposures to higher concentrations of glyphosate, probably due to strong chelating ability of glyphosate or other compounds of formulation. This study allows us to detect the earlier biological effects of glyphosate in the low environmentally realistic concentrations. Further validation of this approach needs the comparison of the results in the ex vivo and in vivo experiments. Keywords: Roundup; bivalve mollusk; cytotoxicity; ex vivo

Inhibition of poly(ADP-ribose)polymerase contributes to the reduction of oxidative stress in murine liver under the conditions of experimental endotoxemia

The aim of the work is to investigate the effect of the enzyme poly(ADP-ribose)polymerase 1 (PARP-1) inhibitor, 4-hydroxyquinazoline (4-HQN), on the state of the pro- and antioxidant system of murine liver, under the conditions of lipopolysaccharide (LPS) induced inflammation. Materials and methods. Systemic endotoxemia was induced by the administration of LPS ( E. coli 0111:B4) at a dose of 3 mg/kg intraperitoneally (IP). A solution of 4-HQN was applied IP at a dose of 100 mg/kg an hour before LPS administration. The processes of lipid peroxidation (LPO) have been evaluated by the content of the end products of LPO in liver tissue by their reaction with thiobarbituric acid (TBA). The concentration of reduced glutathione (GSH) in liver was determined by Ellman's spectrophotometric method. The level of ceruloplasmin (CP) in serum was measured by colorimetric method of Ravin using a test kit (JSC Reagent, Ukraine) in accordance with the manufacturer’s instructions and expressed in mg/l. Results . It was established that 24 hours after LPS administration the content of TBA-reactive substances (TBARS) in liver tissue significantly increased, that indicates intensification of POL. The level of GSH and the activity of CP in serum significantly decreased under the conditions of LPS action. The use of the inhibitor PARP-1, 4-HQN, during endotoxemia resulted in 1.7-fold decrease in the amount of TBARS in liver tissue (P < 0.05 compared with LPS) and increased significantly the GSH content (2.9-fold, P < 0.05) and the CP (1.2-fold, P < 0.05). Conclusions . The data obtained using murine model of endotoxemia indicate the involvement of PARP-1 in intensification of POL. Pharmacological inhibition of this enzyme contributed to the reduction of oxidative stress in murine liver and improved the state of antioxidant protection of the body, that is, it had a pronounced protective effect during endotoxemia.

Вплив вікасолу на активність дегідрогеназ циклу Кребса та стан системи антиоксидантного захисту м’язів шлунка гусей

The aim of work was to study the effect of vicasol on the Krebs cycle dehydrogenase activity and the state of the antioxidant defense system of geese muscle tissue of the stomach. According to the results of the work, it was found in the smooth muscle tissue of the stomach of geese, vicasol increases the activity of glutathione peroxidase, catalase and superoxide dismutase on the 14th and 21st days of ontogenesis, in particular, on the 14th day glutathione peroxidase, catalase and superoxide dismutase activity increase by 181.1 % (p≤0.05), 153.2% (p≤0.05) i 103.3% (p≤0.05), after 7 days 168.0% (p≤0.05), 99.7% (p≤0.05) i 111.3% (p≤0.05) relative to the control group. The antioxidant system enzymes activity of the experimental group on the 28th day tends to decrease, however, a significant difference is observed only between groups of animals for superoxide dismutase, whose activity is reduced by 62.5 % under the influence of vicasol (p≤0.05). On the 35th day of ontogenesis, the activity of glutathione peroxidase and catalase in the experimental group increases by 43.2% (p≤0.05) and 54.1% (p≤0.05) compared to the control, at this time the activity of superoxide dismutase is lower by 23.9 % (p≤0.05). A significant increase in the concentration of lipids hydrogen peroxides (28th day) by 27% (p≤0.05) relative to the control was established in the tissue, followed by a decrease on the 35th day of ontogenesis. Vicasol stabilizes the content of end products of lipid peroxidation in tissue homogenate, with the exception of a decrease of 8.6% (p≤0.05) at the end of experiment. Upon induction of peroxide processes with Fe 2+ in cell, it is increased their content by 108 % (p≤0.05) (21st day), at the end of the experiment, a decrease in the content of secondary lipid decomposition products in the experimental group of animals by 27.5% (p≤0.05). The antioxidant activity of the tissue at the beginning of the experiment under the influence of vicasol was higher by 30%, on the the 21st day decreased by 50% relative to the control group, and on the 35th day it increased by 21,6 %. Vicasol increases the activity of the Krebs cycle dehydrogenase, in particular, succinate dehydrogenase, which activity is higher during the experiment by 14- (78.2%; p≤0.05), 21- (263.3%; p≤0.05), 28- (78, 8%; p≤0.05) and the 35th (92.3%; p≤0.05) day. 2-oxoglutarate dehydrogenase activity are more specific and significantly increases relative to the control group by 14- (122.2%; p≤0.05), 21- (84.4%; p≤0.05) and on the 28th (133.3%; p≤ 0.05) day relative to the control group. In general, vicasol activates the system of antioxidant protection and energy metabolism, that is, it is a complex activator of the body’s metabolic functions.

The research progress on the relationship between 8-iso-prostaglandin F2α, oxidative stress and Henoch-Schonlein purpura

8-iso-prostaglandin F2α is a stable end product of lipid peroxidation of cell membrane lipid arachidonic acid under oxidative stress, which is formed by non-enzymatic beta lysis and recombination.It is an ideal index for evaluating the degree of lipid peroxidation and damage.Oxidative stress can damage biological molecules, cause cell death and tissue damage, and participate in the process of Henoch-Schonlein purpura and kidney damage.This article reviews the oxidative stress state and lipid peroxidation process of the body, the production and significance of 8-iso-prostaglandin F2α, the mechanism of oxidative stress in the pathogenesis of Henoch-Schonlein purpura and renal damage, and the important clinical significance of measuring 8-iso-prostaglandin F2α for Henoch-Schonlein purpura, which will provide evidence for future targeted therapy. Key words: 8-iso-prostaglandin F2α; Oxidative stress; Henoch-Schonlein purpura; Kidney disease

Hydroxypyridinone-Diamine Hybrids as Potential Neuroprotective Agents in the PC12 Cell-Line Model of Alzheimer's Disease.

There is an urgent need to propose effective treatments for Alzheimer’s disease (AD). Although the origin of the disease is poorly understood, several therapeutic options have been proposed. The new therapeutic approaches targeting biometal-mediated neurodegenerative pathways appear to be interesting ones. As a continuation of our preceding studies, two novel series of advanced glycation endproducts (AGE)/advanced lipid peroxidation endproducts (ALE) inhibitors have been developed as multifunctional scavengers. This extended work allowed us to highlight the new hydroxypyridinone-diamine hybrid IIa-3 bearing a C4 alkyl linker between the two pharmacophores. This derivative exhibited preserved potent capacities to trap reactive carbonyl species (vicinal diamine function) as well as reactive oxygen species and transition metals (hydroxypyridinone moiety) in comparison with previously described lead compound 1. In addition, its good predicted absorption, distribution, metabolism and excretion (ADME) properties were correlated with a better efficacy to inhibit in vitro methylglyoxal-induced apoptosis in neuronal-like PC12 cells. This new promising agent revealed improved druglikeness and ability to prevent biometal-mediated oxidative and carbonyl stress amplification involved in AD pathogenesis.

Mesenchymal Stem Cells Decrease Oxidative Stress in the Bowels of Interleukin-10 Knockout Mice.

Background/AimsInflammatory bowel disease (IBD) is an autoimmune disease characterized by chronic inflammation mainly in the large intestine. The interleukin-10 knockout (IL-10 KO) mouse is a well-known animal model of IBD that develops spontaneous intestinal inflammation resembling Crohn’s disease. Oxidative stress is considered to be the leading cause of cell and tissue damage. Reactive oxygen species (ROS) can cause direct cell injury and/or indirect cell injury by inducing the secretion of cytokines from damaged cells. This study evaluated the effects of mesenchymal stem cell (MSC) on the progression of IBD.MethodsIn this study, human bone marrow-derived MSCs were injected into IL-10 KO mice (MSC). Oxidative stress and inflammation levels were evaluated in the large intestine and compared with those in control IL-10 KO mice (CON) and normal wild-type control mice (Wild).ResultsThe levels of ROS (superoxide and hydrogen peroxidase) and a secondary end-product of lipid peroxidation (malondialdehyde) were considerably higher in the CON, while superoxide dismutase and catalase levels were lower in the MSC. Inflammation-related marker (interferon-γ, tumor necrosis factor-α, IL-4, and CD8) expression and inflammatory histological changes were much less pronounced in MSC than in CON.ConclusionsMSCs affect the redox balance, leading to the suppression of IBD.

Betulin attenuated liver damage by prevention of hepatic mitochondrial dysfunction in rats with alcoholic steatohepatitis.

Betulin, a pentacyclic triterpene, possesses antioxidant, anti-inflammatory and hepatoprotective properties. The aim of this study was to evaluate the impact of liver mitochondria in hepatoprotection of betulin using a rat model of alcoholic steatohepatitis induced by ethanol administration (4g/kg, intragastric) for 8weeks. The treatment with betulin (50 and 100mg/kg b.w., intragastric) during this period attenuated the histological signs of steatohepatitis and lowered the serum and liver triglyceride contents, as well as the serum activities of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Betulin (100mg/kg) decreased the liver/body weight ratio and inhibited the increase in the serum levels of TNFα, IL-1β, TGFβ, and hyaluronic acid, demonstrating hepatoprotective, anti-inflammatory, and antifibrotic potential. Betulin also inhibited the formation of superoxide anions in mitochondria and the end-products of lipid peroxidation in liver tissue, the amount of which was significantly increased in ethanol-treated rats. The disturbances in mitochondrial respiration, uncoupling of oxidative phosphorylation and decreasing of mitochondrial complex I, II, and IV activities in rats with steatohepatitis, were reverted by betulin administration. The increased susceptibility of mitochondria to Ca2+-induced permeability transition pore formation in the hepatitis group was improved in rats treated with betulin. In conclusion, betulin, having antioxidant properties, exerts a beneficial effect in the rat model of alcoholic steatohepatitis via prevention of liver mitochondria dysfunction, which may be attributed to the inhibition of mitochondrial permeability transition.

Idebenone improves quality of ram sperm by mitigating oxidative stress during cryopreservation

The present study was designed to test the effect of different levels of idebenone, a potent antioxidant on the quality of ram semen at post thaw. Eighteen (18) ejaculates were collected and extended with tris extender supplemented with no antioxidant (CON), with 2 μM idebenone (Id2), 5 μM idebenone (Id5), 7.5 μM idebenone (Id7.5) and 10 μM idebenone (Id10). The sperm quality was determined in terms of percent sperm motility, live sperm percentage, percent hypoosmotic swelling test (HOST) positive spermatozoa and percent intact acrosome (PIA). Moreover, malondialdehyde (MDA) level, an end product of lipid peroxidation (LPO) was also measured at post thaw both in seminal plasma and sperm cell. At post thaw, the percent sperm motility was significantly higher (p < 0.05) for Id10 as compared to Id2, Id5, Id7.5 and control. The live sperm percentage was non-significantly (p > 0.05) higher for Id10 as compared to control, Id5 and Id7.5 but significantly higher than Id2. The percent HOST positive spermatozoa was significantly higher (p < 0.05) for Id10 than control, Id2 and Id5. The MDA level in seminal plasma was significantly lower (p < 0.05) for Id10 than control and Id2. The MDA level in spermatozoa did show similar trend as in seminal plasma. Further, all the sperm parameters at all idebenone levels declined significantly from pre freeze to post thaw. In conclusion, idebenone at 10 μM level improved post thaw sperm quality by mitigating peroxidative stress, hence could be considered as a promising antioxidant additive for cryopreservation of ram semen.

Tangeretin Inhibits Oxidative Stress and Inflammation via Upregulating Nrf-2 Signaling Pathway in Collagen-Induced Arthritic Rats

Background/Aims: Tangeretin (TAN), a major phytochemical in tangerine peels and an important Chinese herb, has multiple biological properties, especially antioxidative and anti-inflammatory effects. However, the mechanisms remain unclear. Based on these findings, the aim of the present study was to assess the antioxidant and anti-inflammatory properties of TAN in bovine type II collagen-induced arthritis rats. Methods: TAN (50 mg/kg) was given orally once daily for 14 days. The effects of treatment were evaluated by biochemical assay (articular elastase, myeloperoxidase, end products of lipid peroxidation [MDA], antioxidant enzyme, such as superoxide dismutase, catalase, glutathione), nitric oxide, and inflammatory cytokines (interleukin-1β [IL-1β], ­IL-10, tumor necrosis factor-alpha [TNF-α], interferon-γ [IFN-γ], and prostaglandin E2 [PGE2]). The protective effects of TAN against rheumatoid arthritis (RA) were evident from the decrease in arthritis scoring. Furthermore, the Nrf-2 signaling pathway was assessed to illustrate the molecular mechanism. Results: TAN had therapeutic effects on RA by decreasing the oxidative stress damage and regulating inflammatory cytokine expression, including suppression of the accumulation of MDA products, decreasing the IL-1β, TNF-α, IFN-γ, and PGE2 levels, enhancing the IL-10 and the activity of antioxidant enzymes, which was through upregulating Nrf-2 signaling pathway. Conclusion: TAN might have potential as a therapeutic agent for the treatment of RA.

Post-translational inhibition of YAP oncogene expression by 4-hydroxynonenal in bladder cancer cells

The transcriptional regulator YAP plays an important role in cancer progression and is negatively controlled by the Hippo pathway. YAP is frequently overexpressed in human cancers, including bladder cancer. Interestingly, YAP expression and activity can be inhibited by pro-oxidant conditions; moreover, YAP itself can also affect the cellular redox status through multiple mechanisms. 4-Hydroxynonenal (HNE), the most intensively studied end product of lipid peroxidation, is a pro-oxidant agent able to deplete GSH and has an anti-tumoral effect by affecting multiple signal pathways, including the down-regulation of oncogene expressions. These observations prompted us to investigate the effect of HNE on YAP expression and activity. We demonstrated that HNE inhibited YAP expression and its target genes in bladder cancer cells through a redox-dependent mechanism. Moreover, the YAP down-regulation was accompanied by an inhibition of proliferation, migration, invasion, and angiogenesis, as well as by an accumulation of cells in the G2/M phase of cell cycle and by an induction of apoptosis. We also established the YAP role in inhibiting cell viability and inducing apoptosis in HNE-treated cells by using an expression vector for YAP. Furthermore, we identified a post-translational mechanism for the HNE-induced YAP expression inhibition, involving an increase of YAP phosphorylation and ubiquitination, leading to proteasomal degradation. Our data established that HNE can post-translationally down-regulate YAP through a redox-dependent mechanism and that this modulation can contribute to determining the specific anti-cancer effects of HNE.

Intensification of serum albumin amyloidogenesis by a glycation-peroxidation loop (GPL)

The interaction of reducing sugars with proteins leads to the formation of advanced glycation end products (AGE) and reactive oxidative species (ROS). ROS peroxidise free or membrane included unsaturated fatty acids, leading to generate reactive aldehydes as advanced lipid peroxidation end products (ALE). Aldehydes from lipid peroxidation (LPO) react with proteins to cause alteration of protein structure to exacerbate complication of diseases. Here we studied serum albumin glycation in the presence and absence of liposomes as a bio-membrane model to investigate protein structural changes using various techniques including intrinsic and extrinsic fluorescence spectroscopies and electron microscopy analysis. Accordingly, serum albumin glycation and fibrillation were accelerated and intensified in the presence of liposomes through a hypothesized glycation-peroxidation loop (GPL). Together, our results shed light on the necessity of reconsidering diabetic protein glycation to make it close to physiological conditions mimicry, more importantly, proteins structural change due to diabetic glycation is intensified in the proximity of cell membranes which probably potentiates programmed cell death distinct from apoptosis.

Dry Bio-Decontamination Process in Reduced-Pressure O2 Plasma

The main objective of this work was to fully understand the bio-decontamination process in a reduced-pressure oxygen plasma. Gram-negative Escherichia coli species was chosen as the target microorganism in this test. The comparison of decontamination efficacy between plasma total and UV radiation individually under various treatment parameters and tests of DNA agarose electrophoresis were made to evaluate the inactivation effect of UV radiation. The quantity of protein leakage and the concentration of malondialdehyde (MDA), which are markers of the end products of lipid peroxidation, in bacterial suspension after treatment were determined to estimate the contribution of both charged particles and free radicals for bacterial death. In addition, a scanning electronic microscope was used to visualize the plasma effect on microorganisms. The results showed that the essential action of the oxygen plasma on Escherichia coli is believed to be attributed to the fast and intense etching on cell membrane by electrons and ions. Attacks on polyunsaturation fatty acid (PUFA) in the cell membrane by oxygen free radicals and the destruction of the DNA in the cell by UV radiation are accessorial during an effective decontamination process.

AM-1241 CB2 Receptor Agonist Attenuates Inflammation, Apoptosis and Stimulate Progenitor Cells in Bile Duct Ligated Rats.

BACKGROUND:The cannabinoid receptor 2 (CB2) plays a pleiotropic role in the innate immunity and is considered a crucial mediator of liver disease. Cannabinoid CB2 receptor activation has been reported to attenuate liver fibrosis in CCl4 exposed mice and also plays a potential role in liver regeneration in a mouse model of I/R and protection against alcohol-induced liver injury.AIM:In this study, we investigated the impact of CB2 receptors on the antifibrotic and regenerative process associated with cholestatic liver injury.METHODS:Twenty-six rats had bile duct ligation co-treated with silymarin and AM1241 for 3 consecutive weeks. Serum hepatotoxicity markers were determined, and histopathological evaluation was performed.RESULTS:Following bile duct ligation (BDL) for 3 weeks, there was increased aminotransferase levels, marked inflammatory infiltration and hepatocyte apoptosis with induced oxidative stress, as reflected by increased lipid peroxidation. Conversely, following treatment with the CB2 agonist, AM-1241, BDL rats displayed a reduction in liver injury and attenuation of fibrosis as reflected by expression of hydroxyproline and α-smooth muscle actin. AM1241 treatment also significantly attenuated lipid peroxidation end-products, p53-dependent apoptosis and also attenuated inflammatory process by stimulating IL-10 production. Moreover, AM1241 treated rats were associated with significant expression of hepatic progenitor/oval cell markers.CONCLUSION:In conclusion, this study points out that CB2 receptors reduce liver injury and promote liver regeneration via distinct mechanisms including IL-10 dependent inhibition of inflammation, reduction of p53-reliant apoptosis and through stimulation of oval/progenitor cells. These results suggest that CB2 agonists display potent hepatoregenrative properties, in addition to their antifibrogenic effects.

Suppressed hepatocyte proliferation via a ROS-HNE-P21 pathway is associated with nicotine- and cotinine-enhanced alcoholic fatty liver in mice

CYP2A5 is a major enzyme responsible for nicotine and cotinine metabolism in mice. Nicotine and cotinine enhance alcoholic fatty liver in wild type (WT) mice but not in CYP2A5 knockout (KO) mice, and reactive oxygen species (ROS) generated during the CYP2A5-mediated metabolism contributes to the enhancing effect. In combination with ethanol, nicotine and cotinine increased lipid peroxidation end product 4-hydroxynonenal (HNE) in WT mice but not in KO mice. In ethanol-fed KO mice, only 5 and 10 genes were regulated by nicotine and cotinine, respectively. However, in ethanol-fed WT mice, 59 and 104 genes were regulated by nicotine and cotinine, respectively, and 7 genes were up-regulated by both nicotine and cotinine. Plin 2 and Cdkn1a are among the 7 genes. Plin2 encodes adipose differentiation-related protein (ADRP), a lipid droplet-associated protein, which was confirmed to be increased by nicotine and cotinine in WT mice but not in KO mice. Cdkn1a encodes P21 and elevated P21 in nuclei was also confirmed. HNE can increase P21 and P21 inhibit cell proliferation. Consistently, hepatocyte proliferation markers proliferating cell nuclear antigen (PCNA) and Ki67 were decreased in WT mice but not in KO mice by nicotine/ethanol and cotinine/ethanol, respectively. These results suggest that inhibition of liver proliferation via a ROS-HNE-P21 pathway is involved in nicotine- and cotinine-enhanced alcoholic fatty liver.