Amelioration of sodium fluoride induced oxidative stress by Cynometra travancorica Bedd in mice

Objectives Cynometra travancorica, endemic to Western Ghats of India is pharmacologically similar to Saraca asoca and occasionally used as substitute in a well-known Ayurvedic uterine tonic Asokarishta. S. asoca possess various biological properties, but there are no reports on C. travancorica. The present study evaluated the pharmacological properties of C. travancorica and its efficacy in attenuating the sodium fluoride (NaF) induced oxidative stress in mice. Methods Antioxidant potential of methanolic extract of C. travancorica (CTE) stem bark was evaluated using DPPH, superoxide radical scavenging and total antioxidant assays. The effect of CTE on mitigating NaF deteriorated redox status in the liver tissue of mice was evaluated. Functional groups in CTE were analyzed by FTIR analysis. Results CTE effectively scavenged the free radicals in in vitro condition. CTE could augment catalase (46.6%), superoxide dismutase (53.8%) activities and GSH level (48.1%) against NaF induced decline in the liver tissue of mice. The peroxidation of lipids was found to be decreased by 44.9% and tissue damage abated as inferred by histopathology. FTIR analysis revealed the presence of biologically active functional groups in CTE. Conclusions The study revealed the ameliorative effect of C. travancorica against NaF induced deleterious effect in experimental animals by its potent antioxidant potential.

Influence of potential nanopollutant fullerene C60 on physiological and biochemical responses in mammals

The progressive development of technologies in the manufacture and application of nanomaterials in almost all spheres of human life causes penetration in an organism and accumulation of nanoparticles in its cells. Determinations of the risk of using nanomaterials and mechanisms of their cytotoxicity are extremely relevant current problems that should be studied. Fullerene C60 is the most widespread nanomaterial proposed to use inhibition of tumour growth, microbial infections, and purposeful drug delivery. However, there are contradictory data on cytotoxic and/or cytoprotective effects of this fullerene. In the present paper, the action of fullerene C60 on glucose metabolism, the composition of the intestinal microbiota, and an acid-reducing balance were studied in rats. It is shown that fullerene C60 dissolved in olive oil (2 mg/kg/day) induces insulin resistance, activates the peroxidation of lipids in the brain of animals, but not in the liver, under conditions of chronic influence. In addition, fullerene C60 induced changes in the composition of the intestinal microbiota in rats. Determined disorders may be a cause of insulin production, as an adaptive response to the needs of metabolic energy under local oxidative stress in the nerve tissue. At the same time, the growth of insulin resistance can be induced by nonspecific molecular damage in biomembranes and macromolecules, including insulin receptors. In this regard, the explanation of the molecular mechanisms of insulin resistance induced by fullerene C60 together with the effect of fullerene dose will be of particular interest in further studies.

Garlic (Allium sativum L.): Its Chemistry, Nutritional Composition, Toxicity and Anticancer Properties

: The current review discuss the chemistry, nutritional composition, toxicity, and biological functions of garlic and its bioactive compounds against various types of cancers via different anticancer mechanisms. Several scientific documents were found in reliable literature and searched in databases viz Science Direct, PubMed, Web of Science, Scopus and Research Gate were carried out using keywords such as “garlic”, “garlic bioactive compounds”, “anticancer mechanisms of garlic”, “nutritional composition of garlic”, and others. Garlic contains several phytoconstituents with activities against cancer, and these compounds such as diallyl trisulfide (DATS), allicin, and diallyl disulfide (DADS), diallyl sulfide (DAS), and allyl mercaptan (AM). The influence of numerous garlic-derived products, phytochemicals, and nanoformulations on the liver, oral, prostate, breast, gastric, colorectal, skin, and pancreatic cancers has been studied. Based on our search, the bioactive molecules in garlic were found to inhibit the various phases of cancer. Moreover, the compounds in this plant also abrogate the peroxidation of lipids, activity of nitric oxide synthase, epidermal growth factor (EGF) receptor, nuclear factor-kappa B (NF-κB), protein kinase C, and regulate cell cycle and survival signaling cascades. Hence, garlic and its bioactive molecules exhibit the aforementioned mechanistic actions and thus, they could be used to inhibit the induction, development and progression of cancer. The review describes the nutritional Composition of garlic, its bioactive molecules, and nanoformulations against various types of cancers, as well as the potential for developing these agents as antitumor drugs.

Low Doses of Silver Nanoparticles Selectively Induce Lipid Peroxidation and Proteotoxic Stress in Mesenchymal Subtypes of Triple-Negative Breast Cancer

Molecular profiling of tumors shows that triple-negative breast cancer (TNBC) can be stratified into mesenchymal (claudin-low breast cancer; CLBC) and epithelial subtypes (basal-like breast cancer; BLBC). Subtypes differ in underlying genetics and in response to therapeutics. Several reports indicate that therapeutic strategies that induce lipid peroxidation or proteotoxicity may be particularly effective for various cancers with a mesenchymal phenotype such as CLBC, for which no specific treatment regimens exist and outcomes are poor. We hypothesized that silver nanoparticles (AgNPs) can induce proteotoxic stress and cause lipid peroxidation to a greater extent in CLBC than in BLBC. We found that AgNPs were lethal to CLBCs at doses that had little effect on BLBCs and were non-toxic to normal breast epithelial cells. Analysis of mRNA profiles indicated that sensitivity to AgNPs correlated with expression of multiple CLBC-associated genes. There was no correlation between sensitivity to AgNPs and sensitivity to silver cations, uptake of AgNPs, or proliferation rate, indicating that there are other molecular factors driving sensitivity to AgNPs. Mechanistically, we found that the differences in sensitivity of CLBC and BLBC cells to AgNPs were driven by peroxidation of lipids, protein oxidation and aggregation, and subsequent proteotoxic stress and apoptotic signaling, which were induced in AgNP-treated CLBC cells, but not in BLBC cells. This study shows AgNPs are a specific treatment for CLBC and indicates that stratification of TNBC subtypes may lead to improved outcomes for other therapeutics with similar mechanisms of action.

Metabolic changes in the body of cows of patients with metric in the early postpartum period

Purpose: Determination of changes in metabolic status in new-fluxed cows and twisters when metric and the role of oxidant stress in the pathogenesis of inflammation of the uterus.Materials and methods. The two groups of animals 15 goals were investigated in each. The clinical diagnosis of an acute metric in cows and first elevators in the early postpartum period was carried out in cancer of obstetric and gynecological examinations. Blood fences for hematological studies took from cows before morning feeding. General ketone bodies (OCT), beta-hydroxyma acid (BH), acetone with acetoxus acid (ACAC), progesterone, estradiol, testosterone, cortisol; Ketodines and conjugate trimes (cdist), diene conjugates (DK), isolated double bonds and ketodines, malonic dialdehyde (HMDa), glutathione restored and oxidized, soda, catalase, vitamins C and E.Results. With acute metric, in cows and twisters, there is a fatty dystrophy of centrolobular localization in the liver, in which the indicators of EN / ASAS, Oct and VV amounted to 1.9 ± 0.43 mmol / l, 2.49 ± 0.12 and 1.82 ± 0.05 mmol / l, respectively. Large values of the indicators of EN / ASAS, Oct and VN are installed and in the absence of visible fatty dystrophy: 3.8 ± 0.6 mmol / l, 3.22 ± 0.11 and 2.53 ± 0.23 mmol / l, respectively. The asas in the blood of these cows was higher - 0.97 ± 0.07 mmol / l. In cows and primaries patients with metric, MDA content increased by 1.32 times in comparison with indicators in healthy animals of a similar physiological period (p <0.05). At the same time, the catalase is increased (p <0.01) from 24.4 ± 0.23 mm H202 / lchmin to 34.1 ± 0.26 mm H202 / Lchmin. At the same time, the content of vitamin C and E in comparison with the control decreased. So insulated double bonds in patients with cows and first metrics have reliable differences (p <0.05) in the indicators of clinically healthy animals 1,244 ± 0.41 against 1.686 ± 0.42 SL. Units, and conjugate trimes and ketodines with 0.116 ± 0.05 to 0.186 ± 0.07 SL. units. Reducing the superoxiddismutase index is less than a level of 1.55 SL. Ur, also indicates the presence of oxidant stress.Conclusion. According to the data presented, one of the main etiological factors in the pathogenesis of metric in cows and primaries in the early period of Pueerperia is oxidant stress arising from animals against the background of a negative energy balance. Therefore, traditionally used in the algorithm for the diagnosis of animals, patients with metric in the initial postpartum period, biochemical blood biochemical indicators have a lower degree specificity and sensitivity than the parameters of the system "peroxidation of lipids - antioxidant protection".

The role of oxidative stress in the pathogenesis of Graves’ orbitopathy

Graves’ disease (GD) is a chronic autoimmune condition in which the anti-thyroid stimulating hormone receptor antibodies (TRAb) activate the thyrotropin receptor (TSHR) located on thyrocytes, leading to excessive thyroid hormone production. TSHR is also expressed in extrathyroidal tissues, in particular, within the orbit. The serum levels of TRAb correlate with the severity and activity of thyroid orbitopathy (TO). TO is the most common extrathyroidal manifestation of GD. It is an autoimmune inflammation of orbital tissues, that is, extraocular muscles, orbital adipose tissue or a lacrimal gland. Increased orbital fibroblast and adipocyte proliferation, overproduction of glycosaminoglycans, as well as extraocular muscle oedema, result in increased orbital tissue volume and trigger the onset of TO symptoms. The pathophysiology of TO is complex and has not been fully unexplained to date. Orbital fibroblasts show expression of the TSHR, which is the main target of autoimmunity. It has been hypothesised that T-cell activation induced by orbital receptor stimulation by the target antibody results in orbital tissue infiltration, triggering a cascade of events which leads to the production of cytokines, growth factors and reactive oxygen species (ROS). ROS cause damage to many components of the cell: the cell membrane through the peroxidation of lipids and proteins leading to a loss of their function and enzymatic activity. Oxidative stress leads to the activation of the antioxidant system, which operates through two mechanisms: enzymatic and non-enzymatic. Assessment of the concentration of oxidative stress markers and the concentration or activity of anti-oxidative system parameters enables the evaluation of oxidative stress severity, which in the future may be utilized to assess treatment efficacy and prognosis in patients with active OT.

Gender Peculiarities of Protein and Lipid Peroxidation of the Oral Liquid Under the Conditions of Preclinical Iodine and Iron Deficiency

The prevalence of somatic pathology in children increases significantly with each passing year, which is associated with socio-economic, environmental conditions, the complex interaction of exogenous and endogenous factors. This problem may be related to micronutrient imbalances, among which iodine deficiency and sideropenia are quite common. Objective. The aim of the study is to learn the peculiarities of peroxidation of proteins and lipids, the system of antioxidant defence of oral fluid in conditions of preclinical iodine and iron deficiency. Materials and Methods. The study included 115 children aged 6-18 years. The level of peroxidation of proteins was characterized by the content of oxidative modification of protein products (aldehyde derivatives of the main nature) in the oral fluid. Peroxidation of lipids of oral fluid was assessed by the accumulation of diene conjugates (DCs) of polyunsaturated fatty acids and products responding to thiobarbituric acid (TBA-RP). Results. It has been determined that in case of iodine and iron deficiencies, their combination causes significant activation of protein and lipid peroxidation processes in the oral fluid of children, accompanied by an imbalance of the prooxidant-antioxidant system of the oral cavity. Conclusion. Such changes can be predictors of the development of dental pathology

Overproduction of docosahexaenoic acid in Schizochytrium sp. through genetic engineering of oxidative stress defense pathways

Background Oxidation and peroxidation of lipids in microorganisms result in increased levels of intracellular reactive oxygen species (ROS) and reactive aldehydes, and consequent reduction of cell growth and lipid accumulation. Results To reduce oxygen-mediated cell damage and increase lipid and docosahexaenoic acid (DHA) production in Schizochytrium sp., we strengthened the oxidative stress defense pathways. Overexpression of the enzymes thioredoxin reductase (TRXR), aldehyde dehydrogenase (ALDH), glutathione peroxidase (GPO), and glucose-6-phosphate dehydrogenase (ZWF) strongly promoted cell growth, lipid yield, and DHA production. Coexpression of ZWF, ALDH, GPO, and TRXR enhanced ROS-scavenging ability. Highest values of dry cell weight, lipid yield, and DHA production (50.5 g/L, 33.1 g/L, and 13.3 g/L, respectively) were attained in engineered strain OaldH-gpo-trxR by shake flask fed-batch culture; these were increases of 18.5%, 80.9%, and 114.5% relative to WT values. Conclusions Our findings demonstrate that engineering of oxidative stress defense pathways is an effective strategy for promoting cell robustness, lipid yield, and DHA production in Schizochytrium.

Piperine protects oxidative modifications in human erythrocytes

Objectives Piperine (1-piperoyl piperidine), a major alkaloid constituent of Piper nigrum L. and Piper longum L. has pleiotropic biological effects, but the mechanism(s) involved remain to be elucidated. The current study was conducted to examine the efficacy of antioxidant ability of piperine on t-BHP induced markers of oxidative stress in human erythrocytes. Methods Healthy human erythrocytes and erythrocytes membrane was stressed with free radical inducer chemical; t-BHP (10−5 M), and the effects of piperine was measured against free radical mediated modification in lipid and protein content, –SH and GSH value with antioxidant potential. Results The results demonstrate that treatment of erythrocytes with piperine (10−5 to 10−7 M) significantly (p<0.05) ameliorated the adverse consequences of oxidative stress as evidenced by prevention of oxidation of erythrocyte reduced glutathione, membrane thiols, proteins, and peroxidation of lipids; the effects were in correlation with ferric reducing and radical scavenging abilities of piperine. Conclusions The study concludes that piperine possesses potent anti-oxidant potential which may explain many of its observed biological effects.

Ferroptosis: mechanisms and links with diseases

Ferroptosis is an iron-dependent cell death, which is different from apoptosis, necrosis, autophagy, and other forms of cell death. The process of ferroptotic cell death is defined by the accumulation of lethal lipid species derived from the peroxidation of lipids, which can be prevented by iron chelators (e.g., deferiprone, deferoxamine) and small lipophilic antioxidants (e.g., ferrostatin, liproxstatin). This review summarizes current knowledge about the regulatory mechanism of ferroptosis and its association with several pathways, including iron, lipid, and cysteine metabolism. We have further discussed the contribution of ferroptosis to the pathogenesis of several diseases such as cancer, ischemia/reperfusion, and various neurodegenerative diseases (e.g., Alzheimer’s disease and Parkinson’s disease), and evaluated the therapeutic applications of ferroptosis inhibitors in clinics.