As-induced Changes Research Articles

Hyperoside Nanomicelles Alleviate Atherosclerosis by Modulating the Lipid Profile and Intestinal Flora Structure in High-Fat-Diet-Fed Apolipoprotein-E-Deficient Mice.

Atherosclerosis (AS) is a serious threat to human health and the main pathological basis of cardiovascular disease. Hyperoside (Hyp), a flavonoid found mainly in traditional Chinese herbs, can exert antitumor, anti-inflammatory, antioxidant, and cardiovascular-protective effects. Herein, we prepared hybrid nanomicelles (HFT) comprising Hyp loaded into pluronic F-127 and polyethylene glycol 1000 vitamin E succinate and assessed their effects on AS. To establish an AS model, apolipoprotein-E-deficient (ApoE-/-) mice were fed a high-fat diet. We then analyzed the effects of HFT on AS-induced changes in aortic tissues and metabolic markers, simultaneously assessing changes in gut flora community structure. In mice with AS, HFT significantly reduced the aortic plaque area; decreased levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, inflammatory factors, and inducible nitric oxide synthase (NOS); increased high-density lipoprotein cholesterol, endothelial NOS, superoxide dismutase, catalase, and glutathione levels; and promoted the proliferation of beneficial gut bacteria. HFT could regulate intestinal flora structure and lipid metabolism and inhibit inflammatory responses. These beneficial effects may be mediated by inhibiting nuclear factor kappa B signal activation, reducing inflammatory factor expression and improving gut microflora structure and dyslipidemia. The present study provides an empirical basis for the development and clinical application of new dosage forms of Hyp.

An In Vitro and In Silico Perspective Study of Seed Priming with Zinc on the Phytotoxicity and Accumulation Pattern of Arsenic in Rice Seedlings.

Arsenic (As) contamination of the rice agro-ecosystem is a major concern for rice farmers of South East Asia as it imposes a serious threat to human and animal life; thus, there is an unrelenting need to explore the ways by which arsenic stress mitigation could be achieved. In the present investigation, we explore the effect of zinc (Zn2+) supplementation using the seed priming technique for the mitigation of As-induced stress responses in developing rice seedlings. In addition to the physiological and biochemical attributes, we also studied the interactive effect of Zn2+ in regulating As-induced changes by targeting antioxidant enzymes using a computational approach. Our findings suggest that Zn2+ and As can effectively modulate redox homeostasis by limiting ROS production and thereby confer protection against oxidative stress. The results also show that As had a significant impact on seedling growth, which was restored by Zn2+ and also minimized the As uptake. A remarkable outcome of the present investigation is that the varietal difference was significant in determining the efficacy of the Zn2+ priming. Further, based on the findings of computational studies, we observed differences in the surface overlap of the antioxidant target enzymes of rice, indicating that the Zn2+ might have foiled the interaction of As with the enzymes. This is undoubtedly a fascinating approach that interprets the mode of action of the antioxidative enzymes under the metal/metalloid-tempted stress condition in rice by pointing at designated targets. The results of the current investigation are rationally significant and may be the pioneering beginning of an exciting and useful method of integrating physiological and biochemical analysis together with a computational modelling approach for evaluating the stress modulating effects of Zn2+ seed priming on As-induced responses in developing rice seedlings.

Mechanisms of efficient As(III) and As(V) removal by Ni-coprecipitated hausmannite nanocomposites

Being one of the low-valence manganese oxides ubiquitous in surficial environments, hausmannite has high adsorption and redox reactivities towards various contaminants. Natural hausmannite often contains various other cations, such as Ni2+, but it is unclear yet on the crystal chemistry of the foreign cations in the hausmannite structure and as-induced changes in the mineral physicochemical properties and reactivities. In this study, Ni-containing hausmannites were synthesized by Ni2+ coprecipitation with Mn2+, and then were characterized by powder XRD, FTIR, HRTEM, Ni K-edge XAFS, and wet chemical analysis. Then As(V) adsorption and As(III) oxidation behaviors on these nanocomposites were investigated by batch experiments and reaction mechanisms were deciphered by As K-edge XAFS. These nanocomposites have higher points of zero charges and larger specific surface areas than the pristine hausmannite. The dopant mainly exists as α-Ni(OH)2 coatings on the hausmannite surfaces. Compared to the pure hausmannite, these Ni-containing nanocomposites have enhanced As(V) adsorption capacity per unit mass but reduced adsorption affinity and density; while they can also quickly remove As(III) from waters by oxidation, adsorption and fixation, though the initial oxidation rate is slightly reduced. Arsenic immobilized on the mineral surfaces is As(V) and binds with active Mn/Ni sites with an average As-Mn/Ni distances of 3.28–3.30 Å, which can be assigned to bidentate binuclear complexes. These results not only provide new insights into the mediations of As geochemical behaviors by low valence Mn oxide minerals, but also deepen our understanding of the interaction mechanisms of various transition metals with these minerals.

Selenium impedes cadmium and arsenic toxicity in potato by modulating carbohydrate and nitrogen metabolism

Past studies have already determined that selenium (Se) is very effective in alleviating cell oxidative damage caused by various abiotic stresses in plants. Past studies have also indicated other physiological pathways by which Se may benefit plants. In order to better understand the full array of potential applications for Se in agriculture, this study investigated the influence of Se on carbohydrate and nitrogen (N) metabolism in potato plants (Solanum tuberosum L. cv. Sante) grown under cadmium (Cd) and/or arsenic (As) toxicity. Potato plants were grown in a growth chamber and fertigated with Hoagland nutrient solution with or without Se (9 μM). After 48-d of growth under Cd (40 μM) and/or As (40 μM) stress, carbohydrate and N metabolism in leaves, roots and stolons were measured. For carbohydrate metabolism, various sugars—i.e., sucrose, starch, glucose, fructose, and total soluble sugar contents (TSSC)—and the activities of enzymes associated with sucrose metabolism and glycolysis—i.e., acid invertase (AI), neutral invertase (NI), sucrose-synthetase (SS), sucrose phosphatesynthetase (SPS), fructokinase (FK), hexokinase (HK), phosphofructokinase (PFK), and pyruvatekinase (PK)—were measured. For N metabolism, NO3−, NO2− and NH4+ contents along with the enzymatic activities of nitrate reductase (NRA), nitrite reductase (NiRA), glutamine-synthetase (GS), and glutamate-synthetase (GOGAT) were measured. Overall, Cd and/or As treatments had reduced plant growth relative to those plants grown without heavy metal toxicity, due to hindered photosynthesis and alterations in N metabolism and glycolysis. Regarding N metabolism, heavy metal toxicity caused a reduction in NO3− and NO2− content and NRA and NiRA enzymatic activity and enhanced NH4+ content and GDH activity in leaves, roots and stolons. Regarding glycolysis, the activity of enzymes of glycolysis—i.e., FK, HK, PFK, and PK—were also reduced. In the C metabolism study, plants combatted Cd and As toxicity naturally by an adaptation mechanism which caused an increase in soluble sugars (fructose, glucose, sucrose) by increasing NI, SS and SSP enzymatic activity. Supplementation with Se in the Cd and/or As treatments in the carbohydrate and N metabolism studies improved plant growth. Selenium supplementation in the Cd and As treatments decreased Cd and/or As content in the plant tissue and alleviating the Cd- and/or As-induced toxicity by enhancing the C-metabolism adaptation mechanism. Applying Se to Cd and As treatments also decreased nitrogen losses by hindering Cd- and As-induced changes in the N-metabolism. Se also limited Cd and As accumulation in the plant tissue by the antagonistic effect between Cd/Se and As/Se in the roots. The results of this study indicate that in the presence of Cd and/or As. soil toxicity, Se may be a powerful tool for promoting plant growth.

Relation of dietary inorganic arsenic to serum matrix metalloproteinase-9 (MMP-9) at different threshold concentrations of tap water arsenic.

Arsenic (As) exposure is associated with cancer, lung and cardiovascular disease, yet the mechanisms involved are not clearly understood. Elevated matrix metalloproteinase-9 (MMP-9) levels are also associated with these diseases, as well as with exposure to water As. Our objective was to evaluate the effects of dietary components of inorganic As (iAs) intake on serum MMP-9 concentration at differing levels of tap water As. In a cross-sectional study of 214 adults, dietary iAs intake was estimated from 24-h dietary recall interviews using published iAs residue data; drinking and cooking water As intake from water samples and consumption data. Aggregate iAs intake (food plus water) was associated with elevated serum MMP-9 in mixed model regression, with and without adjustment for covariates. In models stratified by tap water As, aggregate intake was a significant positive predictor of serum MMP-9 in subjects exposed to water As≤10 μg/l. Inorganic As from food alone was associated with serum MMP-9 in subjects exposed to tap water As≤3 μg/l. Exposure to iAs from food and water combined, in areas where tap water As concentration is ≤10 μg/l, may contribute to As-induced changes in a biomarker associated with toxicity.

Dietary inorganic arsenic intake in the U.S. and relation to serum matrix metalloproteinase-9 at different threshold concentrations of tap water arsenic

Arsenic (As) exposure is associated with cancer, chronic lung disease and cardiovascular disease, yet the mechanisms involved in As toxicity are not clearly understood. Matrix metalloproteinase 9 (MMP-9) has also been linked to these diseases, and, in earlier studies, we observed: 1) MMP-9 alterations in cultured lung cells exposed to As, 2) a positive association between As in drinking water and increased serum MMP-9 in humans, and 3) that the majority of As exposure in US populations was from food. The objectives of the current study are to evaluate the effects of dietary components of inorganic As intake on serum MMP-9 in subjects with household tap water As concentrations above and below 10 ppb, 5 ppb and 3 ppb. In a cross-sectional study of 215 adult subjects living in Arizona communities, 24-hour dietary intake was analyzed for inorganic As using published residue data, and As in cooking and drinking water was estimated from multisource water samples and reported consumption data. In mixed model regression, the sum of total inorganic As intake was positively associated with serum MMP-9, with and without adjustment for covariates. In adjusted models, dietary protein was a positive predictor and dietary folate, Hispanic ethnicity and age were statistically significant negative predictors. When total inorganic As intake was deconstructed into its component sources--dietary, drinking water and cooking water--, none of the sources were significant predictors. In models stratified by household tap water As, total inorganic As intake was consistently associated with serum MMP-9 among subjects exposed to tap water As below 10 and 5 ppb, but not above. Inorganic As from food alone was significantly associated with serum MMP-9 only among subjects exposed to household tap water As ? 3 ppb. Even in the U.S. where the average tap water As is 2.4 ppb, total inorganic As intake from food and water may contribute to As-induced changes in biomarkers associated with disease.

Influence of Momordica charantia on oxidative stress-induced perturbations in brain monoamines and plasma corticosterone in albino rats

Objectives:The objective of this study was to evaluate the antistress activity of Momordica charantia (MC) fruit extract on stress-induced changes in albino rats and also to explore attenuating effects of MC on in vitro lipid peroxidation in rat brain.Materials and Methods:In this study, Wistar albino rats (180–200 g) were used. Plasma corticosterone and monoamines—5-hydroxy tryptamine (5-HT), norepinephrine (NE), epinephrine (E) and dopamine (DA) in cortex, hypothalamus and hippocampus regions of brain were determined in animals under different stressful conditions. Ethanolic fruit extract of MC, at doses of 200 and 400 mg/kg, was used. The oxidative stress paradigms used in in vivo models were acute stress (AS) and chronic unpredictable stress (CUS). Panax quinquefolium (PQ) was used as a standard in in vivo models and ascorbic acid was used as a reference standard in the in vitro method.Results:Subjecting the animals to AS (immobilization for 150 min once only) resulted in significant elevation of plasma corticosterone levels and brain monoamine levels. Pretreatment with MC at doses of 200 and 400 mg/kg p.o. significantly countered AS-induced changes and a similar effect was exhibited by PQ at 100 mg/kg p.o. In the CUS regimen (different stressors for 7 days), plasma corticosterone levels were significantly elevated whereas the levels of 5-HT, NE, E, and DA were depleted significantly. Pretreatment with MC (200 and 400 mg/kg) attenuated the CUS-induced changes in the levels of above monoamines in cortex, hypothalamus, and hippocampus regions of brain and plasma corticosterone in a dose-dependent manner. Furthermore, MC extract (1000–5000 μg/mL) exhibited a significant quenching effect on in vitro lipid peroxidation indicating its strong antioxidant activity which was compared with ascorbic acid.Conclusions:This study reveals the antistress activity of MC as it significantly reverted the stress-induced changes, and the activity might be attributed to its antioxidant activity since stress is known to involve several oxidative mechanisms.

Adaptogenic effect of Bacopa monniera (Brahmi)

As stress is linked to many diseases, research on an effective antistress agent (adaptogen) from plants has gained importance. We report the investigations on the adaptogenic property of a standardized extract of Bacopa monniera against acute (AS) and chronic stress (CS) models in rats. Panax root powder ( Panax quinquefolium) was taken as a standard. Male SD rats, weighing 180–200 g, exposed to immobilization stress for 150 min once only for AS and for seven consecutive days in CS, were fed with B. monniera or Panax root powder daily for 3 days in AS and for 7 days in CS, 45 min prior to each exposure of stress. Rats were sacrificed immediately after stress, the blood was collected, and the plasma was separated out for biochemical estimation. Adrenals, spleen, and thymus were dissected for organ weight and stomach for ulcer score. AS exposure significantly increased the ulcer index, adrenal gland weight, plasma glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK) but significantly decreased the spleen weight. Pretreatment with B. monniera at 40 mg/kg po significantly reduced the AS-induced increase in the ulcer index, adrenal gland weight, plasma glucose, AST, and CK. A dose of 80 mg/kg po significantly reversed the AS-induced changes in adrenal gland weight, spleen weight, plasma glucose, ALT, and AST. Panax root powder, 100 mg/kg po, significantly reversed the AS-induced changes in spleen weight, plasma ALT, AST, and CK. CS exposure resulted in a significant increase in the ulcer index, adrenal gland weight, plasma AST, and CK with a significant decrease in the thymus and spleen weight, plasma triglyceride, and cholesterol. Pretreatment with low dose of B. monniera extract at 40 mg/kg significantly reversed changes in ulcer index and plasma AST only, whereas the pretreatment with higher dose significantly reversed CS-induced changes in ulcer index, adrenal gland weight, CK, and AST. Panax root powder significantly reversed CS-induced increase in ulcer index, adrenal gland weight, CK, and AST. On the basis of our result, it is concluded that the standardized extract of B. monniera possesses a potent adaptogenic activity.

Arsenic toxicity is enzyme specific and its affects on ligation are not caused by the direct inhibition of DNA repair enzymes

The molecular mechanism of arsenic toxicity is believed to be due to the ability of arsenite [As(III)] to bind protein thiols. Numerous studies have shown that arsenic is cytotoxic at micromolar concentrations. Micromolar As can also induce chromosomal damage and inhibit DNA repair. The mechanism of arsenic-induced genotoxicity is very important because arsenic is a human carcinogen, but not a mutagen, and there is a need to establish recommendations for safe levels of As in the environment. We have measured the dose–response for arsenic inhibition of several purified human DNA repair enzymes, including DNA polymerase β, DNA ligase I and DNA ligase III and have found that most enzymes, even those with critical SH groups, are very insensitive to As. Many repair enzymes are activated by millimolar concentrations of As(III) and/or As(V). Only pyruvate dehydrogenase, one of eight purified enzymes examined so far, is inhibited by micromolar arsenic. In contrast to the purified enzymes, treatment of human cells in culture with micromolar arsenic produces a significant dose-dependent decrease in DNA ligase activity in nuclear extracts from the treated cells. However, the ligase activity in extracts from untreated cells is no more sensitive to arsenic than the purified enzymes. Our results show that direct enzyme inhibition is not a common toxic effect of As and that only a few sensitive enzymes are responsible for arsenic-induced cellular toxicity. Thus, arsenic-induced co-mutagenesis and inhibition of DNA repair is probably not the result of direct enzyme inhibition, but may be an indirect effect caused by As-induced changes in cellular redox levels or alterations in signal transduction pathways and consequent changes in gene expression.