Efficient green photocatalyst of silver-based palladium nanoparticles for methyle orange photodegradation, investigation of lipid peroxidation inhibition, antimicrobial, and antioxidant activity.

Nanotechnology is an interdisciplinary study that has been developing worldwide in recent years and has a serious impact on human life. The fact that the nanoparticles of plant origin are clean, non-toxic, and biocompatible has enabled new fields of study. The Hibiscus sabdariffa (H. sabdariffa) plant has been attracted by scientists because of its impact on health and many other areas. The lipid peroxidation inhibiting activity, antioxidant properties, and antimicrobial properties of H. sabdariffa plant with Ag-Pd metal was ditermined. For the total phenolic component, gallic acid was used as the standard and quarcetin was used for the total flavonoid. The lipid peroxidation inhibition activity of Ag-Pd NPs in ethanol extract was found to be very well compared to the positive control (BHA). The lowest and highest concentrations of DPPH radical scavenging activity were 82.178-97.357%, whereas for BHA these values were found to be 84.142-94.142%. The highest concentration of Ag-Pd NPs at 200 µg/mL the DPPH radical quenching activity was higher than BHA. Ag-Pd NPs showed a good antimicrobial activity against certain pathogenic microorganisms such as Bacillus subtilis, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, which are the causative agents of various diseases in humans. The photodegradation activity of Ag-Pd NPs also investigated against Methyl orange dye (MO) under sunlight irradiation for 120 min and was found to be as 67.88.

A non-canonical vitamin K cycle is a potent ferroptosis suppressor.

Ferroptosis, a non-apoptotic form of cell death marked by iron-dependent lipid peroxidation1, has a key role in organ injury, degenerative disease and vulnerability of therapy-resistant cancers2. Although substantial progress has been made in understanding the molecular processes relevant to ferroptosis, additional cell-extrinsic and cell-intrinsic processes that determine cell sensitivity toward ferroptosis remain unknown. Here we show that the fully reduced forms of vitamin K-a group of naphthoquinones that includes menaquinone and phylloquinone3-confer a strong anti-ferroptotic function, in addition to the conventional function linked to blood clotting by acting as a cofactor for γ-glutamyl carboxylase. Ferroptosis suppressor protein 1 (FSP1), a NAD(P)H-ubiquinone reductase and the second mainstay of ferroptosis control after glutathione peroxidase-44,5, was found to efficiently reduce vitamin K to its hydroquinone, a potent radical-trapping antioxidant and inhibitor of (phospho)lipid peroxidation. The FSP1-mediated reduction of vitamin K was also responsible for the antidotal effect of vitamin K against warfarin poisoning. It follows that FSP1 is the enzyme mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle6. The FSP1-dependent non-canonical vitamin K cycle can act to protect cells against detrimental lipid peroxidation and ferroptosis.

Attenuation of isoprenaline-induced myocardial infarction by Rheum turkestanicum.

BACKGROUND: Oxidative stress plays a major role in the pathogenesis of myocardial infarction. This study evaluated the cardioprotective effects of the hydroalcoholic extract of Rheum turkestanicum on isoprenaline-induced myocardial infarction (MI) in Wistar rats. METHODS: In this study, we used liquid chromatography-mass spectrometry to determine the active compounds present in the extract. Thirty rats were divided to 5 groups (6 rats in each group). The extract was administered orally at the doses of 100 and 300 mg/kg body weight and then a subcutaneous injection of isoprenaline (85 mg/kg) was administered on the 8th and 9th days. Serum levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and creatinine kinase (CPK) were measured using standard commercial kits. Serum activities of superoxide dismutase, catalase, and cardiac levels of thiol and lipid peroxidation were also determined. Hematoxylin and eosin were used for histopathological staining. RESULTS: Phytochemical analysis revealed the presence of 24 compounds in the hydro-ethanolic extract of R. turkestanicum. Isoprenaline increased malondialdehyde (4.002 ± 0178, P < 0.001) while decreased thiol content (101.7 ± 6.186, P < 0.001). Moreover, reduced activities of superoxide dismutase (139 ± 10.88, P < 0.001) and catalase (2.812 ± 0.215, P < 0.001), and elevated levels of LDH (1245 ± 62.28, P < 0.001), CPK (898 ± 23.06, P < 0.001) and CK-MB (697 ± 50.22, P < 0.001) were observed. Pretreatment with the R. turkestanicum extract significantly reduced cardiac markers and increased thiol content as well as the activity of antioxidant enzymes. The extract attenuated the histopathological changes induced by isoprenaline. CONCLUSION: According to the obtained results, R. turkestanicum may be an appropriate candidate to reduce isoprenaline-induced MI through modulation of oxidative stress. Administration of the extract attenuated cardiac enzymes following isoprenaline administration. The cardioprotective action of the extract can be attributed to the bioactive antioxidant ingredients of R. turkestanicum. To identify the precise mechanisms, further investigations are required.

Antiophidic potential of chlorogenic acid and rosmarinic acid against Bothrops leucurus snake venom.

Bothrops leucurus is responsible for most cases of snakebite in Northeast Brazil; however, this species is not included in the pool of venoms used in antivenom production in Brazil. The serotherapy has logistical and effectiveness limitations, which stimulates the search for therapeutic alternatives. Chlorogenic acid and rosmarinic acid present several biological activities, but their antiophidic potential has been poorly explored. Thus, the aim of this approach was to evaluate the potential inhibitory effects of these compounds on B. leucurus venom. Initially, the enzymatic inhibition of toxins was evaluated in vitro. Then, anti-hemorrhagic, anti-myotoxic, and anti-edematogenic assays were performed in vivo, as well analysis of several biochemical markers and hemostatic parameters. In addition, the interaction of inhibitors with SVMP and PLA2 was investigated by docking analysis. Results revealed that compounds inhibited in vitro the enzymatic activities and venom-induced edema, with a decrease in both myeloperoxidase and interleukin quantification. The inhibitors also attenuated the hemorrhagic and myotoxic actions and mitigated changes in serum biochemical and hemostatic markers, as well as decreased lipid peroxidation in liver and kidney tissues. Docking analysis revealed attractive interactions of both inhibitors with the zinc-binding site of SVMP and, in the case of PLA2, chlorogenic acid showed a similar inhibition mechanism to that described for rosmarinic acid. The results evidenced the antiophidic potential of both compounds, which showed higher efficiency than antivenom serum. Thus, both inhibitors are promising candidates for future adjuvants to be used to complement antivenom serotherapy.

TNF antagonist sensitizes synovial fibroblasts to ferroptotic cell death in collagen-induced arthritis mouse models.

Ferroptosis is a nonapoptotic cell death process that requires cellular iron and the accumulation of lipid peroxides. In progressive rheumatoid arthritis (RA), synovial fibroblasts proliferate abnormally in the presence of reactive oxygen species (ROS) and elevated lipid oxidation. Here we show, using a collagen-induced arthritis (CIA) mouse model, that imidazole ketone erastin (IKE), a ferroptosis inducer, decreases fibroblast numbers in the synovium. Data from single-cell RNA sequencing further identify two groups of fibroblasts that have distinct susceptibility to IKE-induced ferroptosis, with the ferroptosis-resistant fibroblasts associated with an increased TNF-related transcriptome. Mechanistically, TNF signaling promotes cystine uptake and biosynthesis of glutathione (GSH) to protect fibroblasts from ferroptosis. Lastly, low dose IKE together with etanercept, a TNF antagonist, induce ferroptosis in fibroblasts and attenuate arthritis progression in the CIA model. Our results thus imply that the combination of TNF inhibitors and ferroptosis inducers may serve as a potential candidate for RA therapy.

Four-Octyl Itaconate Protects Chondrocytes against H2O2-Induced Oxidative Injury and Attenuates Osteoarthritis Progression by Activating Nrf2 Signaling.

Nrf2 is a critical regulator of the antioxidant defense systems in cellular protection. Emerging evidence has shown that four-octyl itaconate (OI) activates Nrf2 cascade. In this study, the chondroprotective effects of OI on H2O2-stimulated chondrocytes and DMM-induced osteoarthritis (OA) progression were investigated. In primary murine chondrocytes, OI interrupted the binding of Keap1 and Nrf2, leading to accumulation and nuclear translocation of Nrf2 protein, as well as transcription and expression of Nrf2-dependent genes, such as HO-1, NQO1, and GCLC. Furthermore, OI inhibited cell death and apoptosis, as well as H2O2-stimulated ROS generation, lipid peroxidation, superoxide accumulation, and mitochondrial depolarization in chondrocytes, which were abolished by the silence or depletion of Nrf2. In addition, in vivo experiments revealed the therapeutic effects of OI on OA progression in a DMM mouse model. Collectively, these results suggested that OI might serve as a potential treatment for OA progression.

The Enzymatic and Non-Enzymatic Antioxidant System Response of the Seagrass Cymodocea nodosa to Bisphenol-A Toxicity.

The effects of environmentally relevant bisphenol A (BPA) concentrations (0.3, 1 and 3 µg L-1) were tested at 2, 4, 6 and 8 days, on intermediate leaves, of the seagrass Cymodocea nodosa. Hydrogen peroxide (H2O2) production, lipid peroxidation, protein, phenolic content and antioxidant enzyme activities were investigated. Increased H2O2 formation was detected even at the lowest BPA treatments from the beginning of the experiment and both the enzymatic and non-enzymatic antioxidant defense mechanisms were activated upon application of BPA. Elevated H2O2 levels that were detected as a response to increasing BPA concentrations and incubation time, led to the decrease of protein content on the 4th day even at the two lower BPA concentrations, and to the increase of the lipid peroxidation at the highest concentration. However, on the 6th day of BPA exposure, protein content did not differ from the control, indicating the ability of both the enzymatic and non-enzymatic mechanisms (such as superoxide dismutase (SOD) and phenolics) to counteract the BPA-derived oxidative stress. The early response of the protein content determined that the Low Effect Concentration (LOEC) of BPA is 0.3 µg L-1 and that the protein content meets the requirements to be considered as a possible early warning "biomarker" for C. nodosa against BPA toxicity.

In vitro and in vivo evaluations of antioxidative, anti-Alzheimer, antidiabetic and anticancer potentials of hydroponically and soil grown Lactuca sativa.

BACKGROUND: Lactuca sativa is an edible plant commonly used by local communities to manage diabetes and stomach problems. METHODS: This work aimed to investigate the anti-oxidant, anticancer, antidiabetic and Anti-Alzheimer effects of hydroponically (HyL) and soil-grown (SoL) Lactuca sativa. Streptozotocin-induced diabetes and AlCl3-induced Alzheimer's disease model was used to evaluate the medicinal effects of Lactuca sativa. RESULTS: HyL showed significant activity in lipid peroxidation assay, DPPH and DNA protection assay, while SoL extract showed moderated activity, respectively. A similar activity response was quantified for α-glucosidase, α-amylase, acetylcholinesterase and butyrylcholinesterase inhibition assays. The cytotoxic potential of HyL and SoL extracts against MCF7, and HePG2 cancer cell lines exhibited significant activity. HyL and SoL showed a substantial decrease in blood glucose levels in streptozotocin-induced diabetic rats. Diabetes-related liver/kidney biomarkers and anti-oxidant enzyme trends moved toward normal after HyL and SoL treatment. In Anti-Alzheimer's based Morris water and elevated plus maze tests, HyL and SoL displayed memory-enhancing response and anti-anxiety behaviour, respectively. HPLC quantification of dopamine and serotonin revealed a moderate but significant (p<0.05) increase in the level of these neurotransmitters in HyL and SoL groups. CONCLUSION: Overall, the study revealed that hydroponic Lactuca sativa possesses the therapeutic potential to treat diseases like Alzheimer's and diabetes.

Assessment of the ameliorative effect of curcumin on pendimethalin-induced genetic and biochemical toxicity.

The present study aimed to assess the toxic effects of pendimethalin herbicide and protective role of curcumin using the Allium test on cytological, biochemical and physiological parameters. The effective concentration (EC50) of pendimethalin was determined at 12 mg/L by the root growth inhibition test as the concentration reducing the root length by 50%. The roots of Allium cepa L. was treated with tap water (group I), 5 mg/L curcumin (group II), 10 mg/L curcumin (group III), 12 mg/L pendimethalin (group IV), 12 mg/L pendimethalin + 5 mg/L curcumin (group V) and 12 mg/L pendimethalin + 10 mg/L curcumin (group VI). The cytological (mitotic index, chromosomal abnormalities and DNA damage), physiological (rooting percentage, root length, growth rate and weight gain) and oxidative stress (malondialdehyde level, superoxide dismutase level, catalase level and glutathione reductase level) indicators were determined after 96 h of treatment. The results revealed that pendimethalin treatment reduced rooting percentage, root length, growth rate and weight gain whereas induced chromosomal abnormalities and DNA damage in roots of A. cepa L. Further, pendimethalin exposure elevated malondialdehyde level followed by antioxidant enzymes. The activities of superoxide dismutase and catalase were up-regulated and glutathione reductase was down-regulated. The molecular docking supported the antioxidant enzymes activities result. However, a dose-dependent reduction of pendimethalin toxicity was observed when curcumin was supplied with pendimethalin. The maximum recovery of cytological, physiological and oxidative stress parameters was recorded at 10 mg/L concentration of curcumin. The correlation studies also revealed positive relation of curcumin with rooting percentage, root length, weight gain, mitotic activity and glutathione reductase enzyme level while an inverse correlation was observed with chromosomal abnormalities, DNA damage, superoxide dismutase and catalase enzyme activities, and lipid peroxidation indicating its protective effect.

Molecular Mechanisms of Action of Selected Substances Involved in the Reduction of Benzo[a]pyrene-Induced Oxidative Stress.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) primarily formed by burning of fossil fuels, wood and other organic materials. BaP as group I carcinogen shows mutagenic and carcinogenic effects. One of the important mechanisms of action of (BaP) is its free radical activity, the effect of which is the induction of oxidative stress in cells. BaP induces oxidative stress through the production of reactive oxygen species (ROS), disturbances of the activity of antioxidant enzymes, and the reduction of the level of non-enzymatic antioxidants as well as of cytokine production. Chemical compounds, such as vitamin E, curcumin, quercetin, catechin, cyanidin, kuromanin, berberine, resveratrol, baicalein, myricetin, catechin hydrate, hesperetin, rhaponticin, as well as taurine, atorvastatin, diallyl sulfide, and those contained in green and white tea, lower the oxidative stress induced by BaP. They regulate the expression of genes involved in oxidative stress and inflammation, and therefore can reduce the level of ROS. These substances remove ROS and reduce the level of lipid and protein peroxidation, reduce formation of adducts with DNA, increase the level of enzymatic and non-enzymatic antioxidants and reduce the level of pro-inflammatory cytokines. BaP can undergo chemical modification in the living cells, which results in more reactive metabolites formation. Some of protective substances have the ability to reduce BaP metabolism, and in particular reduce the induction of cytochrome (CYP P450), which reduces the formation of oxidative metabolites, and therefore decreases ROS production. The aim of this review is to discuss the oxidative properties of BaP, and describe protective activities of selected chemicals against BaP activity based on of the latest publications.

Thymus fontanesii attenuates CCl4-induced oxidative stress and inflammation in mild liver fibrosis.

Liver injury is a major public health problem all over the world that raises the demand of developing novel effective and safe remedies. Traditionally, Thyme (Thymus fontanesii) has a therapeutic potential against different organs toxicity due to its antioxidant activity. The present study aimed to evaluate the antioxidant activities in vitro and the possible hepato-protective effects of T. fontanesii aqueous extract (TFAE) against CCl4 induced liver damage (mild fibrosis) in male albino mice and annotate its phytochemical constituents as well. The extract displayed substantial antioxidant activities in vitro and high content of flavonoids and other phenolic compounds. Oral administration of TFAE (especially high dose) significantly suppressed (but with different degrees) the incidence and severity of CCl4 liver toxicity by activating the hepatic antioxidant defense mechanisms, modulating hepatic functions, and decreasing the production of lipid peroxidation, pro-inflammatory mediators, and pro-fibrotic proteins expression including COL1A1, Fn, and TGF-ß1. These activities might be attributed to the presence of 58 secondary metabolites (identified by LC-MS), mainly phenolic acids, flavonoids and diterpenoids that were able, according to molecular docking, to bind to the inhibitor's binding site of three protein targets involved in liver inflammation and fibrosis. These results showcase the antioxidant and anti-inflammatory properties of Thyme (Thymus fontanesii), illustrate the protective and beneficial effects of the plant against CCl4-induced hepatic toxicity in mice, and support its consumption, traditional uses and promotes its valorization as nutraceutical product.

Adenine overload induces ferroptosis in human primary proximal tubular epithelial cells.

The pathogenesis of crystal nephropathy involves deposition of intratubular crystals, tubular obstruction and cell death. The deposition of 8-dihydroxyadenine (DHA) crystals within kidney tubules, for instance, is caused by a hereditary deficiency of adenine phosphoribosyl transferase in humans or adenine overload in preclinical models. However, the downstream pathobiological patterns of tubular cell attrition in adenine/DHA-induced nephropathy remain poorly understood. In this study, we investigated: (i) the modes of adenine-induced tubular cell death in an experimental rat model and in human primary proximal tubular epithelial cells (PTEC); and (ii) the therapeutic effect of the flavonoid baicalein as a novel cell death inhibitor. In a rat model of adenine diet-induced crystal nephropathy, significantly elevated levels of tubular iron deposition and lipid peroxidation (4-hydroxynonenal; 4-HNE) were detected. This phenotype is indicative of ferroptosis, a novel form of regulated necrosis. In cultures of human primary PTEC, adenine overload-induced significantly increased mitochondrial superoxide levels, mitochondrial depolarisation, DNA damage and necrotic cell death compared with untreated PTEC. Molecular interrogation of adenine-stimulated PTEC revealed a significant reduction in the lipid repair enzyme glutathione peroxidase 4 (GPX4) and the significant increase in 4-HNE compared with untreated PTEC, supporting the concept of ferroptotic cell death. Moreover, baicalein treatment inhibited ferroptosis in adenine-stimulated PTEC by selectively modulating the mitochondrial antioxidant enzyme superoxide dismutase 2 (SOD2) and thus, suppressing mitochondrial superoxide production and DNA damage. These data identify ferroptosis as the primary pattern of PTEC necrosis in adenine-induced nephropathy and establish baicalein as a potential therapeutic tool for the clinical management of ferroptosis-associated crystal nephropathies (e.g., DHA nephropathy, oxalate nephropathy).

The Effect of α-Tocopherol on the Reduction of Inflammatory Processes and the Negative Effect of Acrylamide.

Our research aimed to show acrylamide's influence on inflammatory processes, the oxidative stress it causes in the cholinergic system, and the possibility of reducing inflammation via supplementation with α-tocopherol. For this purpose, an in ovo model was used where the embryos were exposed to acrylamide, α-tocopherol and a cocktail of these substances. After 48 h of exposure, we collected brain samples and performed biochemical assays to examine the effect of the chosen substances on oxidative stress (malondialdehyde-MDA and reduced glutathione-GSH) and acetylcholinesterase activity (AChE). The results showed that acrylamide decreased AChE activity in the examined brain samples by about 25% in comparison to the control group, and this effect was decreased by administering α-tocopherol. The concentration of malondialdehyde significantly increased in the group given acrylamide, while, in the group with α-tocopherol, the observed concentration was lower in comparison to the control group. Moreover, a decrease in glutathione concentration was observed after the administration of acrylamide; however, the protective effect of α-tocopherol was only slightly visible in this case. In conclusion, α-tocopherol minimizes the harmful effects of acrylamide on AchE, and it can minimize the concentration of MDA.

Polyphenolics with Strong Antioxidant Activity from Acacia nilotica Ameliorate Some Biochemical Signs of Arsenic-Induced Neurotoxicity and Oxidative Stress in Mice.

Neurotoxicity is a serious health problem of patients chronically exposed to arsenic. There is no specific treatment of this problem. Oxidative stress has been implicated in the pathological process of neurotoxicity. Polyphenolics have proven antioxidant activity, thereby offering protection against oxidative stress. In this study, we have isolated the polyphenolics from Acacia nilotica and investigated its effect against arsenic-induced neurotoxicity and oxidative stress in mice. Acacia nilotica polyphenolics prepared from column chromatography of the crude methanol extract using diaion resin contained a phenolic content of 452.185 ± 7.879 mg gallic acid equivalent/gm of sample and flavonoid content of 200.075 ± 0.755 mg catechin equivalent/gm of sample. The polyphenolics exhibited potent antioxidant activity with respect to free radical scavenging ability, total antioxidant activity and inhibition of lipid peroxidation. Administration of arsenic in mice showed a reduction of acetylcholinesterase activity in the brain which was counteracted by Acacia nilotica polyphenolics. Similarly, elevation of lipid peroxidation and depletion of glutathione in the brain of mice was effectively restored to normal level by Acacia nilotica polyphenolics. Gallic acid methyl ester, catechin and catechin-7-gallate were identified in the polyphenolics as the major active compounds. These results suggest that Acacia nilotica polyphenolics due to its strong antioxidant potential might be effective in the management of arsenic induced neurotoxicity.

4-hydroxy-2-nonenal as a marker of the oxidative stress in brains of dogs with canine distemper / 4-hidroxi-2-nonenal como marcador de estresse oxidativo no cérebro de cães com cinomose

Canine Distemper is a disease caused by Canine morbillivirus (CM), a pantropic virus that can affect the central nervous system (CNS), causing demyelination. However, the pathogenesis of this lesion remains to be clarified. Brain samples of 14 naturally infected dogs by CM were analyzed to evaluate the presence of oxidative stress and demyelination. RT-PCR assay was performed to confirm a diagnosis of canine distemper in the brain, immunohistochemistry anti-CM was used to localize the viral proteins in the tissue, and anti-4-hydroxy-2-nonenal (4-HNE) was a marker of a product of lipid peroxidation. The results showed the presence of viral proteins in the demyelinated area with the presence of 4-HNE. Our results suggest that the CM virus infection causes oxidative stress leading to lipid peroxidation, which causes tissue damage and demyelination. In conclusion, oxidative stress plays a significant role in canine distemper pathogenesis in the CNS.(AU)

A cinomose canina é uma doença causada pelo Morbilivírus canino (CM), um vírus pantrópico que pode afetar o sistema nervoso central (SNC), causando desmielinização. No entanto, a patogênese dessa lesão não está totalmente esclarecida. RT-PCR e imuno-histoquímica foram realizadas para confirmação do diagnóstico de cinomose em amostras de encéfalo de 14 cães naturalmente infectados. Após confirmação, foi realizada uma avaliação do estresse oxidativo por imuno-histoquímica com uso de anti-4-hidroxi-nonenal (4HNE) como marcador de produtos resultantes da peroxidação lipídica. Os resultados sugerem que a infecção pelo CM causa estresse oxidativo no tecido, levando a peroxidação lipídica, a qual causa danos ao tecido, culminando com desmielinização. Conclui-se que o estresse oxidativo tem papel importante na patogênese da cinomose canina no sistema nervoso central.(AU)

Anti-steroidogenic effects of cholesterol hydroperoxide trafficking in MA-10 Leydig cells: Role of mitochondrial lipid peroxidation and inhibition thereof by selenoperoxidase GPx4.

Steroid hormone synthesis in steroidogenic cells requires cholesterol (Ch) delivery to/into mitochondria via StAR family trafficking proteins. In previous work, we discovered that 7-OOH, an oxidative stress-induced cholesterol hydroperoxide, can be co-trafficked with Ch, thereby causing mitochondrial redox damage/dysfunction. We now report that exposing MA-10 Leydig cells to Ch/7-OOH-containing liposomes (SUVs) results in (i) a progressive increase in fluorescence probe-detected lipid peroxidation in mitochondrial membranes, (ii) a reciprocal decrease in immunoassay-detected progesterone generation, and ultimately (iii) loss of cell viability with increasing 7-OOH concentration. No significant effects were observed with a phospholipid hydroperoxide over the same concentration range. Glutathione peroxidase GPx4, which can catalyze lipid hydroperoxide detoxification, was detected in mitochondria of MA-10 cells. Mitochondrial lipid peroxidation and progesterone shortfall were exacerbated when MA-10 cells were treated with Ch/7-OOH in the presence of RSL3, a GPx4 inhibitor. However, Ebselen, a selenoperoxidase mimetic, substantially reduced RSL3's negative effects, thereby partially rescuing the cells from peroxidative damage. These findings demonstrate that co-trafficking of oxidative stress-induced 7-OOH can disable steroidogenesis, and that GPx4 can significantly protect against this.

Overexpression of the Aldehyde Dehydrogenase Gene ZmALDH Confers Aluminum Tolerance in Arabidopsis thaliana.

Aluminum (Al) toxicity is the main factor limiting plant growth and the yield of cereal crops in acidic soils. Al-induced oxidative stress could lead to the excessive accumulation of reactive oxygen species (ROS) and aldehydes in plants. Aldehyde dehydrogenase (ALDH) genes, which play an important role in detoxification of aldehydes when exposed to abiotic stress, have been identified in most species. However, little is known about the function of this gene family in the response to Al stress. Here, we identified an ALDH gene in maize, ZmALDH, involved in protection against Al-induced oxidative stress. Al stress up-regulated ZmALDH expression in both the roots and leaves. The expression of ZmALDH only responded to Al toxicity but not to other stresses including low pH and other metals. The heterologous overexpression of ZmALDH in Arabidopsis increased Al tolerance by promoting the ascorbate-glutathione cycle, increasing the transcript levels of antioxidant enzyme genes as well as the activities of their products, reducing MDA, and increasing free proline synthesis. The overexpression of ZmALDH also reduced Al accumulation in roots. Taken together, these findings suggest that ZmALDH participates in Al-induced oxidative stress and Al accumulation in roots, conferring Al tolerance in transgenic Arabidopsis.

Curcumin Supplementation (Meriva®) Modulates Inflammation, Lipid Peroxidation and Gut Microbiota Composition in Chronic Kidney Disease.

Chronic kidney disease (CKD) subjects suffer from high risk of cardiovascular mortality, and any intervention preventing the progression of CKD may have an enormous impact on public health. In the last decade, there has been growing awareness that the gut microbiota (GM) can play a pivotal role in controlling the pathogenesis of systemic inflammatory state and CKD progression. To ameliorate the quality of life in CKD subjects, the use of dietary supplements has increased over time. Among those, curcumin has demonstrated significant in vitro anti-inflammatory properties. In this pilot study, 24 CKD patients and 20 healthy volunteers were recruited. CKD patients followed nutritional counselling and were supplemented with curcumin (Meriva®) for six months. Different parameters were evaluated at baseline and after 3-6 months: uremic toxins, metagenomic of GM, and nutritional, inflammatory, and oxidative status. Curcumin significantly reduced plasma pro-inflammatory mediators (CCL-2, IFN-γ, and IL-4) and lipid peroxidation. Regarding GM, after 6 months of curcumin supplementation, Escherichia-Shigella was significantly lower, while Lachnoclostridium was significant higher. Notably, at family level, Lactobacillaceae spp. were found significantly higher in the last 3 months of supplementation. No adverse events were observed in the supplemented group, confirming the good safety profile of curcumin phytosome after long-term administration.

Attenuation of hyperglycemia and amadori products by aminoguanidine in alloxan-diabetic rabbits occurs via enhancement in antioxidant defenses and control of stress.

The micro- and macro-complications in diabetes mellitus (DM) mainly arise from the damage induced by Amadori and advanced glycation end products, as well as the released free radicals. The primary goal of DM treatment is to reduce the risk of micro- and macro-complications. In this study, we looked at the efficacy of aminoguanidine (AG) to prevent the production of early glycation products in alloxan-diabetic rabbits. Type1 DM was induced in rabbits by a single intravenous injection of alloxan (90 mg/kg body weight). Another group of rabbits was pre-treated with AG (100 mg/kg body weight) prior to alloxan injection; this was followed by weekly treatment with 100 mg/kg of AG for eight weeks. Glucose, insulin, and early glycation products (HbA1C and fructosamine) were measured in control, diabetic and AG treated diabetic rabbits. The effects of hyperglycemia on superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), reduced glutathione (rGSH), nitric oxide, lipid peroxides, and protein carbonyl were investigated. Alloxan-diabetic rabbits had lower levels of SOD, CAT, Gpx, and rGSH than control rabbits. Nitric oxide levels were considerably greater. AG administration restored the activities of SOD, CAT, Gpx enzymes up to 70-80% and ameliorated the nitric oxide production. HbA1c and fructosamine levels were considerably lower in AG-treated diabetic rabbits. The observed control of hyperglycemia and amadori adducts in alloxan-diabetic rabbits by AG may be attributed to decrease of stress and restoration of antioxidant defenses.

The edible seaweed Laminaria japonica contains cholesterol analogues that inhibit lipid peroxidation and cyclooxygenase enzymes.

In this study, 5 sterols were isolated and purified from Laminaria japonica, commonly known as edible brown seaweed, and their structures were identified based on detailed chemical methods and spectroscopic analyses. Spectroscopic analyses characterized 5 sterols as 29-Hydroperoxy-stigmasta-5,24(28)-dien-3ß-ol, saringosterol (24-vinyl-cholest-5-ene-3ß,24-diol), 24-methylenecholesterol, fucosterol (stigmasta-5,24-diene-3ß-ol), and 24-Hydroperoxy-24-vinyl-cholesterol. The bioactivities of these sterols were tested using lipid peroxidation (LPO) and cyclooxygenase (COX-1 and -2) enzyme inhibitory assays. Fucosterol exhibited the highest COX-1 and -2 enzyme inhibitory activities at 59 and 47%, respectively. Saringosterol, 24-methylenecholesterol and fucosterol showed higher LPO inhibitory activity at >50% than the other compounds. In addition, the results of molecular docking revealed that the 5 sterols were located in different pocket of COX-1 and -2 and fucosterol with tetracyclic skeletons and olefin methine achieved the highest binding energy (-7.85 and -9.02 kcal/mol) through hydrophobic interactions and hydrogen bond. Our results confirm the presence of 5 sterols in L. japonica and its significant anti-inflammatory and antioxidant activity.