Lipid Peroxidation Product Malondialdehyde Research Articles

Modifying effects of leaf litter extracts from invasive versus native tree species on copper-induced responses in Lemna minor.

Invasive plant species tend to migrate from their native habitats under favourable climatic conditions; therefore, trophic and other relationships in ecosystems are changing. To investigate the effect of natural organic matter derived from native Alnus glutinosa tree species and from invasive in Lithuania Acer negundo tree species on copper toxicity in Lemna minor, we analysed the dynamics of Cu binding in aqueous leaf litter extracts (LLE) and plant accumulation, morphophysiological parameters, and antioxidative response. The results revealed that A. glutinosa LLE contained polyphenols (49 mg pyrogallol acid equivalent (PAE)/g DM) and tannins (7.5 mg PAE/g DM), while A. negundo LLE contained only polyphenols (23 mg PAE/g DM). The ability of LLE to bind Cu increased rapidly over 1.5–3 h to 61% and 49% of the total Cu concentration (6.0 ± 0.9 mg/L), respectively for A. glutinosa (AG) and A. negundo (AN), then remained relatively stable until 48 h. At the same time, L. minor accumulated 384, 241 or 188 µg Cu/g FW when plants were exposed to Cu (100 µM CuSO4), Cu with 100 mg/L dissolved organic carbon (DOC) from either AG LLE or AN LLE, accordingly. Catalase (CAT) and guaiacol peroxidase (POD) played a dominant role in hydrogen peroxide scavenging when plants were exposed to Cu and 10 or 100 mg/L DOCAG mixtures in both the first (up to 6h) and the second (6–48 h) response phases. Due to functioning of oxidative stress enzymes, the levels of the lipid peroxidation product malondialdehyde (MDA) reduced in concentration-dependent manner, compared to Cu treatment. When combining Cu and DOCAN treatments, the most sensitive enzymes were POD, ascorbate peroxidase and glutathione reductase. Their activities collectively with CAT were sufficient to reduce MDA levels to Cu-induced in the initial, but not the second response phase. These data suggest that leaf litter extracts of different phenolic compositions elicited different antioxidant response profiles resulting in different reductions of Cu stress, thus effecting L. minor frond and root development observed after seven days. The complex data from this study may be useful in modelling the response of the aquatic ecosystem to a changing environment.

Cannabidiol protects keratinocyte cell membranes following exposure to UVB and hydrogen peroxide

Keratinocytes, the major cell type of the epidermis, are particularly sensitive to environmental factors including exposure to sunlight and chemical agents. Since oxidative stress may arise as a result of these factors, compounds are actively sought that can act as protective agents. Recently, cannabidiol (CBD), a phytocannabinoid found in Cannabis Sativa L., has gained increased interest due to its anti-inflammatory and antioxidant properties, and absence of psychoactive effects. This prompted us to analyze the protective effects of CBD on keratinocytes exposed to UVB irradiation and hydrogen peroxide. Here we show, using liquid chromatography mass spectrometry, that CBD was able to penetrate keratinocytes, and accumulated within the cellular membrane. CBD reduced redox balance shift, towards oxidative stress, caused by exposure UVB/hydrogen peroxide, estimated by superoxide anion radical generation and total antioxidant status and consequently lipid peroxidation level. CBD was found to protect keratinocytes by preventing changes in the composition of the cellular membrane, associated with UVB/hydrogen peroxide damages which included reduced polyunsaturated fatty acid levels, increased sialic acid and lipid peroxidation products (malondialdehyde and 8-isoprostanes) levels. This maintains cell membranes integrity and prevents the release of lactate dehydrogenase. In addition, CBD prevented UVB/hydrogen peroxide-induced reduction of keratinocyte size and zeta potential, and also decreased activity of ATP-binding cassette membrane transporters. Together, these findings suggest that CBD could be a potential protective agent for keratinocytes against the harmful effects of irradiation and chemical environmental factors that cause oxidative stress.

Clopidogrel Prophylaxis Abates Myocardial Ischemic Injury and Inhibits the Hyperlipidemia-Inflammation Loop in Hypercholestrolemic Mice

Platelet hyper adhesiveness orchestrates with inflammation and vascular muscle proliferation leading to atheroma formation and endothelial dysfunction. The current study aims to compare the prophylactic role of Aspirin and Clopidogrel therapy against isoproterenol-induced acute myocardial infarction (AMI), in mice on high-fat, cholesterol-rich diet (HFD-C). The animals received HFD-C with Aspirin or Clopidogrel for 8weeks and were subjected to AMI by isoproterenol. The blood lipids, inflammatory cytokines, myocardial enzymes, redox state, long pentraxin (PTX3), and matrix metalloproteinases (MMP-2 and MMP-9) activities were investigated. Antiplatelet therapy moderated the hyperlipidemia induced by HFD-C in the current study. Essentially, the total cholesterol and LDL-C levels were lower with Aspirin than with Clopidogrel therapy. Yet Aspirin and Clopidogrel each comparably lowered CK-MB, AST, MMP-2, MMP-9, and the lipid peroxidation product malondialdehyde (MDA) in the hyperlipidemic animals exposed to AMI. However, the decline in cTn-T, LDH and PTX3 levels was greater after Clopidogrel than Aspirin administration. Therefore, Clopidogrel provides greater protection against AMI than Aspirin in the hyperlipidemic mice. This could be explained by the suppression of the proinflammatory cytokines IL-6, TNF-α, TGF-1β and stabilization of the extracellular matrix through the inhibition of MMP-2 and MMP-9 activities. Furthermore, Clopidogrel demonstrated significant antioxidative action in the AMI animals, resulting in diminished MDA production and preserved CAT activity. Beside its therapeutic role in the thrombotic vascular events, Clopidogrel confers significant protection against ischemic myocardial injury by counteracting the platelet-mediated inflammation and oxidative stress associated with HFD-C consumption in animals.

Protective effect of Tualang honey against cadmium-induced morphological abnormalities and oxidative stress in the ovary of rats

BackgroundTo investigate the protective effects of Tualang honey against the toxicity effects induced by cadmium (Cd) on the ovary.MethodsA total of 32 female Sprague Dawley rats were taken and randomly divided into four groups (n = 8). Throughout the experimental period of 6 weeks, negative control-NC (vehicle deionized water), positive control-CD (Cd at 5 mg/kg), Tualang honey followed by Cd exposure-TH (Tualang honey at 200 mg/kg and Cd at 5 mg/kg) and Tualang honey control-THC (Tualang honey at 200 mg/kg) groups, were administered orally on a daily basis.ResultsRats exposed to Cd were significantly higher in ovarian weight, number of antral and atretic follicles as compared to the NC group. The disruptive effects of Cd on ovarian follicles were associated with a disruption in gonadotropin hormones and decreases in follicular stimulating hormone (FSH) and luteinizing hormone (LH). Moreover, a significant formation of oxidative stress in ovarian Cd-exposed rats has been proven by increasing the level of lipid peroxidation products (malondialdehyde) and decreasing the levels of enzymatic antioxidant (catalase). Interestingly, a daily supplementation of high antioxidant agents such as Tualang honey in these animals, caused significant improvements in the histological changes. Additionally, less atretic follicles were observed, restoring the normal level of LH and FSH (P < 0.001), and normalizing the ovarian malondialdehyde (P < 0.05) and catalase levels in comparison with CD group (P < 0.05).ConclusionsTualang honey has protective effects against Cd-induced ovarian toxicity by reducing morphological abnormalities, restoring the normal levels of gonadotropin hormones and stabilizing equilibrium levels of lipid peroxidation and antioxidant enzyme in ovaries of rats.

Changes of liver transcriptome profiles following oxidative stress in streptozotocin-induced diabetes in mice.

BackgroundOxidative-stress (OS) was causal in the development of cell dysfunction and insulin resistance. Streptozotocin (STZ) was an alkylation agent that increased reactive oxygen species (ROS) levels. Here we aimed to explore the oxidative-stress and related RNAs in the liver of STZ-induced diabetic mice.MethodsRNA-sequencing was performed using liver tissues from STZ induced diabetic mice and controls. Pathway and Gene Ontology (GO) analyses were utilized to annotate the target genes. The differentially expressed RNAs involved in the peroxisome pathway were validated by qRT-PCR. The glucose metabolite and OS markers were measured in the normal control (NC) and STZ-induced diabetic mellitus (DM) group.ResultsThe levels of serum Fasting insulin, HbA1c, Malondialdehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α) were significant higher in DM groups than NC group, while SOD activity decreased significantly in DM groups. We found 416 lncRNAs and 910 mRNAs were differentially expressed in the STZ-induced diabetic mice compared to the control group. OS associated RNAs were differentially expressed in the liver of STZ-induced diabetic mice.ConclusionThis study confirmed that the OS was increased in the STZ-induced DM mice as evidenced by the increase of lipid peroxidation product MDA and 8-iso-PGF2α, identified aberrantly expressed lncRNAs and mRNAs in STZ-induced diabetic mice.

Protective effect of ginsenoside Rk1, a major rare saponin from black ginseng, on cisplatin-induced nephrotoxicity in HEK-293 cells.

Cisplatin, as one of the most effective chemotherapeutic agents, its clinical use is limited by serious side effect of nephrotoxicity. Cisplatin-induced nephrotoxicity is closely related to apoptosis induction and activation of caspase. The present study aimed to explore the potential protective effect of ginsenoside Rk1 (Rk1), a rare ginsenoside generated during steaming ginseng, on cisplatin-induced nephrotoxicity and the underlying mechanisms in human embryonic kidney 293 (HEK-293) cells. Our results showed that the reduced cell viability induced by cisplatin could significantly recover by Rk1. Furthermore, glutathione (GSH) as an oxidative index, was elevated and the lipid peroxidation product malondialdehyde (MDA) was significantly decreased after Rk1 treatment compared to the cisplatin group. Additionally, Rk1 can also decrease the ROS fluorescence expression and increase the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) compared to the cisplatin group, which suggested a suppression of oxidative response. More importantly, the cisplatin-induced elevated protein levels of Bax, cleaved caspase-3, cleaved caspase-9, and decreased protein level of Bcl-2 were reversed after treatment with Rk1. Our results elucidated the possible protective mechanism of Rk1 for the first time, which may involve in its anti-oxidation and anti-apoptosis effects.

Salvianolic acid B ameliorates psoriatic changes in imiquimod-induced psoriasis on BALB/c mice by inhibiting inflammatory and keratin markers via altering phosphatidylinositol-3-kinase/protein kinase B signaling pathway.

Salvianolic acid B (SAB) is an active phytocomponent of a popular Chinese herb called Radix Salvia militiorrhiza with numerous biological properties. The anti-psoriasis activity of SAB was examined by evaluating various psoriasis inflammatory and keratin markers against imiquimod (IMQ)-induced psoriasis on BALB/c mice. Totally 50 healthy BALB/c mice were evenly divided into 5 groups including control, drug control (SAB; 40 mg/kg), IMQ-induced psoriasis (5%), IMQ exposure and treated with SAB (40 mg/kg), or standard methotrexate (MTX; 1 mg/kg). Mice supplemented with either SAB or MTX significantly lowered the values of psoriasis area severity index (PASI), erythema, scaling, skin thickness, inflammatory markers (interleukin [IL]-22/23/17A/1β/6) and lipid peroxidation product (malondialdehyde). Also, IMQ exposed BALB/c mice treated with SAB or MTX display lesser histopathological changes with enhanced antioxidant activities (catalase, superoxide dismutase). Moreover, the protein expression of keratin markers (K16 and K17) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling proteins (pAkt/Akt and pPI3K/PI3K) were significantly downregulated after administration with SAB and MTX as compared with IMQ induced mice. Taking together, SAB and MTX significantly ameliorate psoriatic changes by inhibiting psoriatic inflammatory and keratin markers through abolishing PI3K/Akt signaling pathway. However, further studies (clinical trials) are needed to confirm the anti-psoriatic property of SAB before recommending to psoriasis patients.

Synergistic action of indole acetic acid with homobrassinolide in easing the NaCl-induced toxicity in Solanum melongena L. seedlings

In the current work, the influence of indole-3-acetic acid (IAA; 10–5 M) and 28-homobrassinolide (HBL; 10–8 M) alone or in combination was explored in Solanum melongena L. seedlings treated with sodium chloride (NaCl). The NaCl at different concentrations (5 mM and 15 mM) reduced growth attributes, photosynthetic pigments as well as photosynthesis, and enhanced the dark respiratory rate, and these effects were accompanied with Na+ and reactive oxygen species (ROS) accumulation in leaf tissues. Moreover, NaCl reduced the proficiency of PS II with the increasing doses of selected stress which is apparent from the declined values of Fv/Fm (Phi_P0), Ѱ0 (Psi_0), ϕE0 (Phi_E0) and PIABS, and augmented values of energy fluxes: ABS/RC, ET0/RC, TR0/RC and DI0/RC. The NaCl treatment caused substantial reduction in nitrate and nitrite contents, activities of nitrate reductase, nitrite reductase, glutamine synthetase and glutamate synthase, and increased ammonium content and glutamate dehydrogenase activity. Enhanced level of ROS, i.e. superoxide radical (O2•−) and hydrogen peroxide (H2O2) under NaCl stress amplified the lipid peroxidation product malondialdehyde (MDA), in spite of considerable upsurge in performance of superoxide dismutase, peroxidase, catalase, glutathione-S-transferase enzymes and amount of non-protein thiol, cysteine and proline. Exogenous supplementation of IAA and HBL considerably assuaged the NaCl-induced collapse in growth attributes by manipulating the structural and functional features of photosynthetic apparatus. The ameliorating effect of IAA and HBL, in combination, was due to (1) substantial decrease in Na+ accumulation, (2) improvement in PS II efficiency and nitrogen metabolism and (3) reduced oxidative damage in S. melongena L. due to stimulatory response of antioxidants that keeps the level of oxidants under limit in the seedlings. Thus, the overall results campaigned that IAA and HBL act synergistically to overcome the toxic effects that NaCl had on S. melongena L. seedlings.

Simulated remote ischemic preconditioning inhibits Smad2 and enhances post‐hypoxic autophagy and survival of H9c2 cells

BackgroundCardiomyocyte apoptosis is considered as one the major forms of cell deaths of myocardial ischemia/reperfusion (I/R) injury. Remote ischemic preconditioning (RIPC) protects the cardiomyocytes from I/R injury that involves the enhancement of autophagy, but the underlying mechanism and especially the relationship with apoptosis has not been delineated. Smad2 is an important autophagy regulatory protein, but its role in RIPC is unknown.MethodsRat cardiac myoblast H9c2 cells hypoxia/reoxygenation (H/R) injury model was established with 6 hours of hypoxia followed by 12 hours of normoxia reoxygenation to mimic I/R injury. The cells in the conditioning group were exposed to 3 cycles of 10 minutes of alternating nitrogen‐flushed hypoxia and reoxygenation as stimulated RIPC (sRIPC) 24 hours before inducing prolonged H/R. The cell viability, oxidative damage, inflammatory markers, expressions of apoptosis and autophagy‐related proteins were assessed.ResultsH/R caused significant cell injury in untreated control H9c2 cells that was associated reduced autophagy (reduction in the ratio of LC3‐II to LC3‐I) and sRIPC enhanced post‐hypoxic cell survival, reduced reactive oxygen species formation and oxidative damage manifested as increased lipid peroxidation product Malondialdehyde (MDA), inhibited Smad2 transcriptional repressor activity, activated Beclin‐1 and autophagy but reduced apoptotic cell death (all p &lt; 0.05).ConclusionsIt is concluded that inhibition of Smad2 and the subsequent activation of autophagy may represent a mechanism by which sRIPC attenuate post‐hypoxic cardiomyocyte injury.Support or Funding InformationFunding: This study was supported by grants NSFC(81800245 and 81670770), and in part by Health and Medical Research Fund (HMRF, 05161826)

ANTIOXIDANT EFFECT OF PHOTODYNAMIC THERAPY IN TREATMENT OF RADIATION-INDUCED ULCERS INFECTED WITH S. AUREUS

We studied the systemic effect of photodynamic therapy (PDT) in experimental animals at PDT local exposure on their radiation-induced ulcer (the local skin irradiation dose of 85.0 Gr) infected with S. aureus. Lipid peroxidation (LPO) products (malondialdehyde, diene conjugates) were determined in blood serum. LPO levels were measured by conventional techniques. It was found that the values of pro oxidant markers concentration (2.0-2.5 fold increased diene conjugates level, 30-40 % increased malondialdehyde content in the infected group), which dramatically increased after local irradiation of the outer surface of thigh and, especially, after infection of the wound surface, at PDT treatment restored to normal levels. Keywords: infected radiation ulcer, photodynamic therapy (PDT), lipid peroxidation (LPO), malondialdehyde (MDA), diene conjugates (DC).

Immunomodulatory and antioxidant effects of Astragalus polysaccharide liposome in large yellow croaker (Larimichthys crocea)

Astragalus polysaccharides (APS) have been widely used as immunopotentiators in aquaculture, however, the best way of their administration remains to be explored. In the present study, APS liposome (APSL) was prepared by film dispersion-ultrasonic method. The optimal conditions of APSL preparation were determined by response surface methodology, with a ratio of 10:1 (w/w) for soybean lecithin to APS and 8:1 (w/w) for soybean lecithin to cholesterol, and an ultrasound time of 15 min, which produced an encapsulation efficiency of 73.88 ± 0.88% of APSL. In vivo feeding experiments in large yellow croaker showed that both APS and APSL could enhance the contents of serum total protein (TP) and albumin (ALB), activities of serum non-specific immune enzymes such as acid phosphatase (ACP), alkaline phosphatase (AKP), and lysozyme (LZM), and phagocytic activity of head kidney macrophages. Meanwhile, they both increased the activities of serum antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and reduced the content of final lipid peroxidation product malondialdehyde (MDA) in serum, thus exhibiting the antioxidant effects. In vitro experiments on primary head kidney macrophages (PKM) showed that both APS and APSL inhibited ROS production, but obviously enhanced NO production and phagocytic activity of PKM. Furthermore, expression levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α), IFN-γ, and iNOS in PKM were significantly up-regulated after APS and APSL treatments, but no expression change of IFN-h was observed. Taken together, our results showed that both APS and APSL could improve several immune parameters and antioxidant ability of large yellow croaker either in vivo or in vitro, and the efficacy of APSL was markedly better than APS. These findings therefore indicated that the immunomodulatory and antioxidant activities of APS could be enhanced after encapsulated with liposome, and APSL may represent a potential drug delivery system of APS for development of immunoenhancers in aquaculture.

Nitrogen Oxide Donor Enhances Cold-Induced Changes in Antioxidant and Osmoprotective Systems of Cereals

The effect of priming winter rye (Secale cereale L., var. Pamiat’ Khudoerko) and wheat (Triticum aestivum L., var. Dosconala) seeds with nitrogen oxide (NO) donor sodium nitroprusside (SNP) on their frost resistance was studied. The NO donor at concentrations of 0.1–0.5 mM increased the cold-hardening ability of seedlings of both cereals (6 days at 2–4°С), leading to a significant increase in their survival after freezing at –6 and –8°С. Seed treatment with SNP contributed to an increase in the content of sugars, proline, anthocyanins, and UV-B absorbing flavonoids in cereal seedlings. An increase in the activity of superoxide dismutase and guaiacol peroxidase in them was also detected. After cold hardening, especially after freezing, the content of the lipid peroxidation product malondialdehyde in seedlings grown from seeds primed with SNP was lower than in the corresponding controls. It was concluded that nitrogen oxide enhanced the cold-induced activation of antioxidant and osmoprotective systems of cereals.

State of antioxidant system in triticale seedlings at cold hardening of varieties of different frost resistance

Effect of cold hardening on state of antioxidant system (AOS) of triticale (× Triticosecale Wittmack) seedlings of varieties, differed in frost resistance, namely Buket and Raritet (winter, high-frost-resistant), and Alexandra and Pidzymok Kharkovskiy (facultative, less resistant) was studied. In absence of cold hardening, a clear connection between studied indicators of the AOS state and frost resistance of the varieties was not observed. After hardening of seedlings at 2–4 °C for 6 days, the activity of superoxide dismutase (SOD) and catalase increased in the high-frost-resistant varieties Buket and Raritet. In less resistant ones—Alexandra and Pidzymok Kharkovskiy—the activity of these enzymes changed less significantly. At the same time, the activity of guaiacol peroxidase increased more noticeably after hardening in these varieties. Hardened seedlings of the Buket, Raritet and Alexandra varieties had significantly higher sugar content than the Pidzymok Kharkovskiy. The proline content in response to cold hardening increased in all varieties, while the absolute values in the varieties Buket, Raritet and Pidzymok Kharkovskiy were significantly higher than in the Alexandra. Cold hardening caused a significant increase in the content of anthocyanins and flavonoids, absorbing in UV-B, in the Buket, Raritet and Alexandra, but not in the Pidzymok Kharkovskiy. The content of lipid peroxidation product malondialdehyde after a 6-h damaging action of − 7 °C increased in the varieties Alexandra and Pidzymok Kharkovskiy and slightly changed in the Buket and Raritet. In general, a positive relationship was found between AOS activity and frost resistance of hardened triticale seedlings. This relationship was most clearly manifested for indicators of SOD activity and flavonoid content.

Heterogeneous astaxanthin distribution in the fillet of Atlantic salmon post-smolt at elevated temperature is not affected by dietary fatty acid composition, metabolic conversion of astaxanthin to idoxanthin, or oxidative stress

Farmed Atlantic salmon in Tasmania are exposed to elevated water temperatures during summer, which is often associated with reduced pigmentation quality. This study tested the effects of the factors: temperature (elevated, 19.4 °C (ET) vs. control, 15.2 °C), dietary fatty acid (FA) composition (diet 1, high in fish oil vs. diet 2, low in fish oil) and fillet cut (anterior/dorsal cut; ADCT and dorsal Norwegian quality cut (dNQC)) on the concentration of astaxanthin (Axn) in white muscle of salmon post-smolt. After fish doubled initial weights (212 g) at each temperature, the concentration of Axn in muscle was not affected by dietary FA composition, but was higher at ET and higher in the dorsal NQC at ET. In contrast, Axn concentrations between these fillet cuts were the same at the control temperature. The concentration of long chain polyunsaturated FA, which are prone to peroxidation, was generally higher in the fish fed the diet high in fish oil, and in the anterior/dorsal cut. However, the relationships between these FA within triglycerides and phospholipids and the lipid peroxidation product malondialdehyde in white muscle were poor. Further, the concentrations of malondialdehyde showed a poor relationship with Axn in white muscle. There was no idoxanthin in any of the white muscle samples at the analytical detection limit of 0.1 mg/kg.In summary, ET led to higher concentrations of Axn in white muscle, but also to heterogeneous Axn concentrations between the fillet cuts tested. The concentration of Axn in white muscle was not affected by the dietary FA composition and was not associated with oxidative stress or metabolic conversion into idoxanthin in this tissue under the conditions tested. When Axn was expressed per unit of crude protein, the concentration of Axn was higher in the dorsal NQC at ET, indicating that differences of myofibrillar white muscle proteins in their capacity to bind pigment carotenoids may have contributed to the heterogeneous pigment deposition in fillet at ET.Global sea temperatures are anticipated to rise in the future and the implications for aquaculture production must be understood. This study demonstrated the significant effects of temperature on the deposition of pigment carotenoids over the fillet of salmon.

Increased Oxidative Stress, Altered Trace Elements, and Macro-Minerals Are Associated with Female Obesity.

Generally female individuals are more prone to obesity due to their lifestyle and physiology. However, female individuals have got little attention in this aspect. This pioneering study designed to find the level of serum malondialdehyde (MDA), non-enzymatic antioxidant (vitamin C), other trace elements (zinc and iron), and macro-minerals (sodium, potassium, and calcium) for female obesity determining its role and action in disease diagnosis along with propagation. For this prospective case-control study, 70 female obese and 70 healthy individuals were evaluated. Serum lipid peroxidation product malondialdehyde (MDA) concentration was measured to determine the level of lipid peroxidation. UV spectrophotometric method was implemented for vitamin C concentration to measure serum ascorbic acid. Atomic absorption spectroscopy (AAS) was implemented to determine serum macro-minerals (Na, K, and Ca), and trace elements (Zn and Fe) were estimated. For statistical analysis, student's t-test and Pearson's correlation test were executed. A significantly higher concentration of serum MDA (p < 0.001) and low concentration of antioxidants (vitamin C) (p < 0.001) are observed in patient than control group. We found a lower concentration of trace elements (zinc, iron) and macro-minerals (sodium, potassium, and calcium) in patients compared to control except sodium. The mean concentrations for serum Zn, Fe, Na, K, and Ca were 0.34 ± 0.01, 0.25 ± 0.01, 3828.91 ± 205.09, 90.42 ± 6.45, and 43.04 ± 2.38mg/L and 0.78 ± 0.08, 0.84 ± 0.08, 2600.97 ± 99.79, 223.79 ± 14.64, and 86.43 ± 2.78mg/L, respectively, for female obese patients and control subjects (p < 0.001). We can suggest from our study that there is a strong association of female obesity with increased serum concentrations of MDA and reduced non-enzymatic antioxidant vitamin C and different serum trace metals and macro-minerals.

Rare Ginsenoside 20(R)-Rg3 Inhibits D-Galactose-Induced Liver and Kidney Injury by Regulating Oxidative Stress-Induced Apoptosis.

Oxidative stress is considered as a major factor in aging and exacerbates aging process through a variety of molecular mechanisms. D-galactose, a normal reducing sugar with high dose can cause the accumulation of reactive oxygen species (ROS) or stimulate free radical production indirectly by the formation of advanced glycation end products in tissues, finally resulting in oxidative stress. 20(R)-ginsenoside Rg3 (20(R)-Rg3), a major and representative component isolated from red ginseng (Panax ginseng C.A Meyer), has been shown to observably have an anti-oxidative effect. We thereby investigated the beneficial effects of 20(R)-Rg3 on D-galactose-induced oxidative stress injury and its underlying mechanisms. Our results showed that continuous injection of D-galactose with 800[Formula: see text]mg/kg/day for 8 weeks increased the levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN). However, such increases were attenuated by the treatment of 20(R)-Rg3 for 4 weeks. Meanwhile, 20(R)-Rg3 markedly inhibited D-galactose-caused oxidative stress in liver and kidney. The anti-oxidants, including catalase (CAT) and superoxide dismutase (SOD), were elevated in the mice from 20(R)-Rg3-treated group compared with that from D-galactose group. In contrast, a significant decrease in levels of cytochrome P450 E1 (CYP2E1) and the lipid peroxidation product malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were observed in the 20(R)-Rg3-treated group. These effects were associated with a significant increase of AGEs. More importantly, 20(R)-Rg3 effectively attenuated D-galactose induced apoptosis in liver and kidney via restoring the upstream PI3K/AKT signaling pathway. Taken together, our study suggests that 20(R)-Rg3 may be a novel and promising anti-oxidative therapeutic agent to prevent aging-related injuries in liver and kidney.

Traditional Chinese Medicine Fuzheng Huayu Prevents Development of Liver Fibrosis in Mice.

Aim:To investigate the therapeutic effect of FZHY on hepatic fibrosis in mice and to determine the mechanism of its action.Methods:Wild type mice were subjected to toxic (carbon tetrachloride, CCl4) or cholestatic (bile duct ligation, BDL). Upon induction of liver fibrosis, mice were treated with FZHY (4.0g/kg, 2w, oral gavage) or vehicle (PBS). Livers were analyzed by Sirius Red staining, immunostaining and RT-PCR for profibrogenic and pro-inflammatory genes. The effect of FZHY on hepatocytes, inflammatory responses, activation of fibrogenic myofibroblasts, and ROS production was assessed.Results:FZHY strongly inhibited the development of CCl4- and BDL-induced liver fibrosis in mice. Liver fibrosis was significantly improved in FZHY-treated mice, as demonstrated by reduced content of hepatic hydroxyproline and Sirius Red positive area. Moreover, the number of SMA +and Desmin+ myofibroblasts was significantly reduced in the livers of FZHY-treated mice, and correlated with downregulation of the mRNA levels of α-SMA, collagen-α1(I), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), TGF-β1 and its receptor TGF-βRI, and platelet-derived growth factor-β (PDGF-β), suggesting that FZHY inhibits activation of fibrogenic myofibroblasts. Furthermore, administration of FZHY markedly decreased recruitment of F4/80+ inflammatory macrophages to the livers of CCl4- and BDL-injured mice, and this effect was associated with downregulation of monocyte chemoattractant protein-1(MCP-1) and macrophage inflammatory protein-1 (MIP-1) mRNA. In addition, the lipid peroxidation products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) were reduced, demonstrating that treatment with FZHY can effectively block ROS production in livers of CCl4- and BDL-injured mice.Conclusions:Traditional Chinese Medicine FZHY has a variety of anti-fibrotic effects, including strong anti-oxidant, anti-inflammatory and anti-fibrotic effects on myeloid cells and hepatocytes. Although FZHY compound does not seem to directly affect HSCs, it regulates HSC activation via inhibition of macrophage recruitment to fibrotic liver.

Citric Acid Protects Dopaminergic Cells against Rotenone-Induced Neurodegeneration

We investigated the effect of citric acid on rotenone-induced oxidative stress and neuro- and hepato-toxicity. Swiss mice received subcutaneous injections of rotenone at a dose of 1.5 mg/kg once every other day for two weeks either alone or in combination with citric acid at 200 or 400 mg/kg given orally. The control group was treated with the vehicle dimethyl sulfoxide. The brain and liver levels of the lipid peroxidation product malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (TAC), and paraoxonase-1 (PON-1) activity were measured and as well as brain striatal concentrations of nuclear factor-kappa B (NF-kB) and tyrosine hydroxylase. Histopathology of the brain and liver tissue was also performed. Results indicated that MDA and NO content were increased whereas TAC and PON-1 decreased in the brain and liver tissue following rotenone injection. There was also increased NF-kB and decreased tyrosine hydroxylase concentrations in the brain of rotenone-treated mice. Rotenone-treated mice showed decreased striatal cell size and pyknotic nuclei. There were also interstitial hemorrhage and focal inflammatory cells infiltration in cerebral cortex, and degenerated neurons in cortex and hippocampus. The liver exhibited inflammatory cell infiltration and fibrosis. The administration of citric acid protected against rotenone-induced histopathological changes, decreased MDA, NO, and increased TAC and PON-1 activity in the brain and liver. It also reduced NF-kB and increased tyrosine hydroxylase in the brain of rotenone-treated mice. These data indicate that citric acid prevents rotenone-induced neuronal and liver damage via a decrease in oxidative stress. These findings suggest that supplementation with citric acid could be of value in the prevention of neuronal cell death in Parkinson’s disease.

PSXIII-3 Maternal eicosapentaenoic acid feeding decreases placental and fetal lipid deposition and improves antioxidant capacity through a Sirtuin-1 independent

Abstract This research aimed to evaluate whether maternal dietary n-3 polyunsaturated fatty acids (PUFA) supplementation could decrease placental lipid deposition and improve placental antioxidant capacity through a SIRT1-dependent way. In the present study, male and female SIRT1+/- mice were mated overnight, then primiparous SIRT1+/- mice were fed a 60% kcal high-fat-diet (HFD) or equienergy EPA diet (4.4% EPA-ethyl ester) (n = 22/each group). At pregnant 18.5 d, retro-orbital blood samples were obtained then sacrificed by cervical dislocation. Placentas and its corresponding fetuses were collected by caesarean section. We found that the EPA diet significantly changed maternal plasma, placenta and fetus fatty acid composition, and decreased placental and fetal lipid content. Meanwhile, EPA treatment significantly increased placental and fetal antioxidant capacity, however, lipid peroxidation products malondialdehyde was also increased. Moreover, EPA treatment significantly activated placental UCP1 and PGC1α expression and alleviated mitochondrial swelling induced by HFD. SIRT1 knockout had no significant effect on placental lipid content, but notably decreased fetal triglyceride (TG) and non-esterified fatty acid (NEFA) content. Meanwhile, SIRT1 knockout significantly decreased the ratio of n-3 PUFA in placenta. SIRT1 knockout also significantly decreased PGC1α mRNA and protein level and increased mitochondrial swelling. Both EPA treatment and SIRT1 deficiency had no effect on BODIPY-FL-C16 (a fluorescent labeled palmitic acid) uptake in placenta and fetus. No significant effect was observed between diet and genotype. In conclusion, our study demonstrated that maternal EPA feeding decreased placental and fetal lipid deposition and improved antioxidant capacity through a Sirtuin-1 independent mechanism.

A small-molecule activator of mitochondrial aldehyde dehydrogenase 2 reduces the severity of cerulein-induced acute pancreatitis

Acute pancreatitis (AP) is one of the leading causes of hospital admission for gastrointestinal disorders. Although lipid peroxides are produced in AP, it is unknown if targeting lipid peroxides prevents AP. This study aimed to investigate the role of mitochondrial aldehyde dehydrogenase 2 (ALDH2), a critical enzyme for lipid peroxide degradation, in AP and the possible underlying mechanisms. Cerulein was used to induce AP in C57BL/6 J male mice and pancreatic acinar cells were used to elucidate underlying mechanisms in vitro. Pancreatic enzymes in the serum, lipid peroxidation products malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), and Bcl-2, Bax and cleaved caspase-3 were measured. ALDH2 activation with a small-molecule activator, Alda-1, reduced the levels of the pancreatic enzymes in the serum and the lipid peroxidation products MDA and 4-HNE. In addition, Alda-1 decreased Bax and cleaved caspase-3 expression and increased Bcl-2 expression in vivo and in vitro. In conclusion, ALDH2 activation by Alda-1 has a protective effect in cerulein-induced AP by mitigating apoptosis in pancreatic acinar cells by alleviating lipid peroxidation.