Increase In Glutathione Content Research Articles

Repeated psychosocial stress causes glutamic acid decarboxylase isoform-67, oxidative-Nox-2 changes and neuroinflammation in mice: Prevention by treatment with a neuroactive flavonoid, morin

Psychosocial stress and biological predispositions are linked to mood and personality disorders related to psychiatric behaviors. Targeting neuroinflammation and oxidative stress has been recognized as a potential strategy for the prevention of psychosocial stress-induced psychiatric disorders. Morin, a bioactive compound isolated from mulberry leaf has been shown to produce antiamnesic, antipsychotic and anti-inflammatory effects relative to ginseng, a well-known adaptogen. Hence, the present study investigated the effect of morin on social-defeat stress (SDS)-induced behavioral, neurochemical, neuroimmune and neurooxidative changes in mice using intruder-resident paradigm. The intruder male mice were distributed into 6 groups (n = 10). Groups 1 (normal-control) and 2 (SDS-control) received normal saline, groups 3–5 had morin (25–100 mg/kg) while group 6 received ginseng (50 mg/kg) intraperitoneally daily for 14 days. Thirty minutes after treatment from days 7–14 onwards, mice in groups 2–6 were exposed to SDS for 10 min physical and psychological confrontations respectively with aggressive-resident mice. Neurobehavioral effects (locomotor activity, cognitive performance, anxiety- and depressive-like behavior) were assessed on day 14. Biomarkers of oxidative/nitrergic stress and neuroinflammation; acetylcholinesterase (AChE) and glutamic-acid decarboxylase-67 (GAD67) were measured in the striatum, prefrontal-cortex and hippocampus. Behavioral deficits induced by SDS were attenuated by morin and ginseng. Both morin and ginseng decreasedmalondialdehyde, nitrite levels and increased glutathione concentrations in the brain regions. They also reduced inflammatory mediators (TNF-α, IL-6, COX-2 and NF-κB), AChE activity and Nox-2 expression in the specific brain regions. However, morin increased the levels of GAD67 in the striatum, prefrontal-cortex and hippocampus in contrast to ginseng. Our results suggest that morin mitigates SDS-induced neurobehavioral deficits through enhancement of GAD67, inhibition of AChE activity, oxidative stress, Nox-2 and neuroinflammatory pathways.

Prostaglandin E2 affects in vitro maturation of bovine oocytes

The role of prostaglandin E2 (PGE2) in the successful resumption of oocyte meiosis and cumulus expansion has been well-documented. However, there remains very little information available on the influence of PGE2 on other processes that occur during oocyte maturation. In this study, we supplemented a maturation medium with PGE2 and monitored oocyte quality markers, glucose metabolism, mitochondrial status, oxidative stress, and apoptosis in the cumulus-oocyte complexes (COCs), using a well-established in vitro model of embryo production in cattle. We found that this increased availability of PGE2 during maturation led to an increase in the expression of genes associated with oocyte competence and improved the quality of blastocysts produced. Prostaglandin E2 also appeared to stimulate glucose uptake and lactate production in the COCs, both influencing the expression of enzymes involved in glycolysis and the hexosamine biosynthetic pathway. We found that PGE2 reduced intracellular reactive oxygen species levels, and simultaneously increased glutathione concentration and stimulated antioxidant gene expression in the oocyte. These results indicate that PGE2 has an important role in the protection of oocytes against oxidative stress. Mitochondrial membrane potential was also improved in PGE2-treated oocytes, and there was a reduction in the occurrence of apoptosis in the COCs. Promotion of an anti-apoptotic balance in transcription of genes involved in apoptosis was present in both oocytes and the cumulus cells. In summary, PGE2 could represent a novel autocrine/paracrine player in the mechanisms that can facilitate successful oocyte maturation and oocyte survival in the cow.

Xanthotoxin and umbelliferone attenuate cognitive dysfunction in a streptozotocin-induced rat model of sporadic Alzheimer's disease: The role of JAK2/STAT3 and Nrf2/HO-1 signalling pathway modulation.

The aim of the present study was to assess the neuroprotective effects of xanthotoxin and umbelliferone in streptozotocin (STZ)-induced cognitive dysfunction in rats. Animals were injected intracerebroventricularly (ICV) with STZ (3 mg/kg) once to induce a sporadic Alzheimer's disease (SAD)-like condition. Xanthotoxin or umbelliferone (15 mg/kg, i.p.) were administered 5 hr after ICV-STZ and daily for 20 consecutive days. Xanthotoxin or umbelliferone prevented cognitive deficits in the Morris water maze and object recognition tests. In parallel, xanthotoxin or umbelliferone reduced hippocampal acetylcholinestrase activity and malondialdehyde level. Moreover, xanthotoxin or umbelliferone increased glutathione content. These coumarins also modulated neuronal cell death by reducing the level of proinflammatory cytokines (tumour necrosis factor-alpha and interleukin-6), inhibiting the overexpression of inflammatory markers (nuclear factor κB [NF-κB] and cyclooxygenase II), and upregulating the expression of NF-κB inhibitor (IκB-α). Interestingly, xanthotoxin diminished phosphorylated JAK2 and phosphorylated STAT3 protein expression, while umbelliferone markedly replenished nuclear factor erythroid-derived 2-like 2 (Nrf2) and haem oxygenase-1 (HO-1) levels. The current study provides evidence for the protective effect of xanthotoxin and umbelliferone in STZ-induced cognitive dysfunction in rats. This effect may be attributed, at least in part, to inhibiting acetylcholinestrase and attenuating oxidative stress, neuroinflammation and neuronal loss.

BSC2 enhances cell resistance to AmB by inhibiting oxidative damage in Saccharomyces cerevisiae

Amphotericin B has been the gold standard for the treatment of invasive mycosis for many years. Its resistance mechanisms are reported to be mainly related to the decrease of ergosterol content or the changes of cell wall. Previous study has shown that Saccharomyces cerevisiae strain lack of BSC2 was sensitive significantly to Amphotericin B. In the present study, the role of BSC2 on Amphotericin B resistance were investigated. We found that BSC2 enhanced the resistance of yeast cells to Amphotericin B, which was not related to cellular ergosterol content. BSC2 can maintain the permeability of mitochondrial membrane and cell membrane integrity by inhibiting the accumulation of intercellular reactive oxygen species and alleviating the production of lipid peroxidation and superoxide radical. These alterations were attributed to the enhancement of the activities of superoxide dismutase, catalase and glutathione peroxidase, and the increased glutathione content. Taken together, BSC2 inhibits oxidative damage induced by Amphotericin B through increasing activities of antioxidant enzymes and levels of GSH to alleviate the accumulation of reactive oxygen species, lipid peroxidation and superoxide radical, resulting in the maintenance of mitochondrial membrane potential and cell membrane integrity. However, Amphotericin B resistance mediated by BSC2 is independent of Yap1p, GSH1 and Hog1p. The results demonstrate for the first time that BSC2 enhances cell resistance to Amphotericin B by inhibiting oxidative damage in yeast. Our findings improve current understanding of the mechanism of Amphotericin B resistance and provide potential strategy for reducing Amphotericin B resistance.

Antioxidant defense in the eyes of immunocompetent and immunosuppressed mice infected with Acanthamoeba spp.

BackgroundAcanthamoeba spp. are ubiquitous pathogens which cause granulomatous amoebic encephalitis and disseminated infection. Moreover, Acanthamoeba spp. infection of the cornea leads to Acanthamoeba keratitis. Our previous study showed that the infection of an eyeball may also take place via the migration of trophozoites through the optic nerve from the brain to the eyes. The aim of the study was to analyze the activity of enzymatic antioxidants and the concentration of non-enzymatic antioxidant in the eyes of immunocompetent and immunocompromised mice with disseminated acanthamoebiasis.ResultsIn the immunocompetent mice infected with Acanthamoeba spp. we noted a significant decrease in catalase activity at 8 and 16 days post-infection (dpi). Glutathione reductase activity was significantly lower at 16 dpi compared to the control group and glutathione concentration was statistically higher at 24 dpi than in the control group. In the immunosuppressed mice, a statistically significant increase in glutathione concentration in the eye samples was found at 16 dpi compared to those not infected with Acanthamoeba spp. In the immunosuppressed mice infected with Acanthamoeba spp., glutathione peroxidase activity was statistically lower at 8 dpi, and glutathione concentration was statistically significantly higher at 16 dpi compared to the control group.ConclusionsThe inflammatory response in the eyes of hosts with experimental acanthamoebiasis led to changes in the activity of enzymatic antioxidants and the content of non-enzymatic antioxidant. Therefore, the dysregulation of antioxidants may play a role in the pathomechanism of Acanthamoeba eye infection.

HPLC fingerprint analysis of Phyllanthus emblica ethanol extract and their antioxidant and anti-inflammatory properties

Ethnopharmacological relevancePhyllanthus emblica L. (P. emblica) as a medical plant has been used to treat diseases in Asia. It is famous for a wide range of biological activities, especially for its antioxidant and anti-inflammatory activity. However, quality control underlying the bioactivity of P. emblica fruits remains to be studied. Materials and methodsIn this study, we evaluated the HPLC fingerprint and bioactivity of polyphenols extracted from P. emblica fruits grown in different habitats. ResultsP. emblica fruits collected from 10 different habitats in Guangdong, Fujian, Yunnan, and Guangxi provinces in China were used to establish a simple and reliable HPLC fingerprint assay. Simultaneous quantification of three monophenols was also performed to determine assay quality and consistency. Additionally, chemical assessment of the different ethanolic extract (PEEE) from 10 P. emblica fruits demonstrated that they exhibited antioxidant activity by enhancing reducing power and total antioxidant capacity, scavenging hydroxyl radical and superoxide anion. PEEE protected RAW264.7 cells from oxidative damage by increasing glutathione content and total superoxide dismutase activity, suppressing MDA content. PEPE also alleviated lipopolysaccharide-induced inflammation in RAW 264.7 cells by decreasing release of pro-inflammatory mediators. Notably, the PEEE samples from Yunnan province showed the optimal antioxidant and anti-inflammatory effects among all the PEEE samples. ConclusionIn conclusion, The PEEE HPLC fingerprint may help improve P. emblica quality control, and P. emblica with antioxidant and anti-inflammatory activities may be potentially applied in functional foods or in adjuvant therapy for medicinal development.

Protective effects of dietary supplementation with a silicate clay mineral (palygorskite) in lipopolysaccharide-challenged broiler chickens at an early age

Palygorskite (Pal), a silicate clay mineral abundant in the natural world, has been recently receiving increased attention in animal production. The aim of the present study was to evaluate the effects of Pal supplementation on growth performance, organ weight, inflammatory response, intestinal barrier function, and antioxidant capacity of broilers challenged with lipopolysaccharide (LPS) at an early age. In total, 144 1-day-old male broiler chicks were allocated to one of three treatment groups consisting of six replicates of eight chicks each. The three treatments were: 1) non-challenged broilers fed basal diet (control group); 2) LPS-challenged broilers fed basal diet; 3) LPS-challenged broilers fed basal diet supplemented with 10 g/kg Pal. Broilers were injected intraperitoneally with LPS at a dosage of 1 mg/kg body weight or an equivalent amount of saline (control group) at 17, 19, and 21 days of age. LPS challenge resulted in inferior growth performance to that of the control group (body weight at 21 days of age, 721 g vs 657 g; gain-to-feed ratio, 0.68 vs 0.59), and higher relative weights of liver and spleen in broilers (P < 0.05). Pal supplementation did not improve growth performance (body weight at 21 days of age, 657 g vs 660 g; gain-to-feed ratio, 0.59 vs 0.61) or decrease the relative organ weight of LPS-challenged broilers (P> 0.05). Furthermore, LPS treatment increased interleukin-1β concentration in serum and ileal mucosa, and interferon-γ concentration in jejunal mucosa (P < 0.05). In contrast, the concentrations of interleukin-1β in serum and interferon-γ in jejunal mucosa in LPS-challenged broilers were reduced by Pal supplementation (P < 0.05). LPS challenge increased the abundance of interferon-γ and claudin-3 mRNA in jejunal mucosa, but reduced zonula occludens-1 mRNA expression in ileal mucosa (P < 0.05). These changes in mRNA abundance of the aforementioned genes in LPS-challenged broilers were normalized on Pal supplementation (P < 0.05). LPS injection increased serum d-lactic acid concentration in broilers (P < 0.05), and this increase was reversed by Pal supplementation (P < 0.05). LPS challenge also increased malondialdehyde accumulation in serum and jejunal mucosa, but reduced glutathione concentration in jejunal and ileal mucosa of broilers (P < 0.05). In contrast, dietary Pal supplementation decreased malondialdehyde accumulation, but increased glutathione concentration in jejunal mucosa of LPS-challenged broilers (P < 0.05). It can, therefore, be concluded that Pal can be added to diets of LPS-challenged young broiler chickens to reduce inflammation and improve antioxidant capacity.

Regulation of oxidative-restorative processes in secondary fermentation of wine materials in sparkling wine technology

The expediency of using preparations of dry inactivated (cell walls) yeast - glutaroma, salcline, bioproject, elivite and activite in the technology of sparkling wines produced by classical and reservoir methods has been studied. Decreased activity of redox potential is found when using said preparations irrespective of method of secondary fermentation. The greatest effect is noted in the combined use of cell wall preparations and bentonite suspension. The use of glutaroma and elivite, as well as mixtures thereof with bentonite, provided the highest amount of antioxidant activity of sparkling wine in both secondary fermentation methods. During the secondary fermentation of the control sample, an increase in glutathione content was observed in the first 2 weeks, after which its concentration remained virtually unchanged for 90 days of observation. The introduction into circulation of glutaroma, activite, bioproject, salcline, activated the fermentation process, and the concentration of reduced glutathione increased. A marked increase in glutathione concentration was found in the combined use of bentonite suspension with glutaroma, elivite and bioprotect. The increase in glutathione content was observed during the whole period of observation. On the basis of the obtained data, the mechanisms of oxidation-reduction process in production of sparkling wines by classical and reservoir methods are justified.

Evaluation of metabolic changes in liver and serum of streptozotocin-induced diabetic rats after Mango diet supplementation

Abstract Mango consumption has shown bioactive properties against several diseases like diabetes, therefore, we evaluated how a mango-supplemented diet affects metabolic pathways in diabetic rats. Serum and liver samples were collected from 26 rats divided into 3 groups (healthy, untreated diabetic and mango-treated diabetic) after dietary intervention and analysed using an LC-MS untargeted metabolomic strategy. Twenty-six and 29 metabolites in serum and liver were potentially annotated, showing significant differences among groups. Several affected pathways were due to the disease state [fatty acids (i.e. palmitoleic, linolenic, stearidonic, eicosapentaenoic, docosahexaenoic acids and others), bile acids (i.e. glycocholic acid) and amino acids (i.e. leucine, isoleucine and valine)], and others due to mango supplementation (increased hepatic bioaccumulation of euxanthone, a mangiferin metabolite, and increased glutathione concentration). These results suggest that a mango-supplemented diet exerted a significant antioxidant effect in the liver of diabetic rats, likely due to its phenolic compounds, like mangiferin and its metabolites.

The SGLT2 Inhibitor Empagliflozin Ameliorates the Inflammatory Profile in Type 2 Diabetic Patients and Promotes an Antioxidant Response in Leukocytes.

Sodium–glucose co-transporter 2 inhibitors (iSGLT2) have been linked to a considerable reduction in cardiovascular risk in patients with type 2 diabetes (T2D), but the precise molecular mechanisms are still elusive. We aimed to evaluate the effects of the iSGLT2 empagliflozin on systemic inflammation and its potential antioxidant properties. This is an observational, prospective follow-up study of a cohort of fifteen patients with T2D who received 10 mg/day of empagliflozin according to standard clinical care. Measures at baseline, 12 and 24 weeks were taken. Metabolic and anthropometric parameters were evaluated. Production of mitochondrial superoxide, glutathione content, and glutathione s-reductase and catalase mRNA levels were measured in leukocytes. Serum levels of myeloperoxidase, hs-CRP and IL-10 were determined. In addition to decreased body weight and reduced glucose and HbA1c levels, we observed a reduction in superoxide production in leukocytes of diabetic patients and increased glutathione content, prominently after 24 weeks of empagliflozin treatment. Leukocyte expression of glutathione s-reductase and catalase, and serum levels of IL-10 were enhanced at 24 weeks of empagliflozin treatment. Concomitantly, reduced hs-CRP and myeloperoxidase levels were seen. This study provides evidence of the antioxidant and anti-inflammatory properties of empagliflozin treatment in humans, which may contribute to its beneficial cardiovascular effects.

Synergistic activation of mitochondrial metabolism and the glutathione redox couple protects HepG2 hepatocarcinoma cells from palmitoylcarnitine-induced stress.

Fatty acid stress can have divergent effects in various cancers. We explored how metabolic and redox flexibility in HepG2 hepatocarcinoma cells mediates protection from palmitoylcarnitine. HepG2 cells, along with HCT 116 and HT29 colorectal cancer cells were incubated with 100 μM palmitoylcarnitine for up to 48 h. Mitochondrial H2O2 emission, glutathione, and cell survival were assessed in HT29 and HepG2 cells. 100 μM palmitoylcarnitine promoted early growth in HepG2 cells by ~8% after 48 h versus decreased cell survival observed in HT29 and HCT 116 cells. Palmitoylcarnitine increased mitochondrial respiration at physiological and maximal concentrations of ADP, while lowering cellular lactate content in HepG2 cells, suggesting a switch to mitochondrial metabolism. HepG2 cell growth was associated with an early increase in H2O2 emission by 10 min, followed by a decrease in H2O2 at 24 h that corresponded with increased glutathione content, suggesting a redox-based compensatory mechanism. In contrast, abrogation of HT29 cell proliferation was related to decreased mitochondrial respiration (likely due to cell death) and decreased glutathione. Concurrent glutathione depletion with BSO prevented palmitoylcarnitine-induced growth in HepG2 cells, indicating that glutathione was critical for promoting growth following palmitoylcarnitine. Inhibiting UCP2 with genipin sensitized HepG2 cells to palmitoylcarnitine, suggesting that activation of UCP2 may be a 2nd redox-based mechanism conferring protection. These findings suggest that HepG2 cells possess inherent metabolic and redox flexibility relative to HT29 cells that confers protection from palmitoylcarnitine-induced stress via adaptive increases in mitochondrial respiratory control, glutathione buffering, and induction of UCP2.

Genistein improves viability, proliferation and mitochondrial function of cardiomyoblasts cultured in physiologic and peroxidative conditions.

Phytoestrogens exert protective effects on the cardiovascular system through mechanisms that have yet to be clearly demonstrated. The aim of this study was to evaluate the protective effects exerted by genistein on cardiomyoblasts (H9C2) against oxidative stress, nitric oxide (NO) release, viability, proliferation/migration and mitochondrial function. H9C2 cultured in physiological or peroxidative conditions, were treated with genistein in the absence or presence of estrogen receptors (ERs), G protein‑​coupled‑estrogenic‑receptors (GPER), Akt, extracellular‑​signal‑regulated kinases 1/2 (ERK1/2) and p38 mitogen activated protein kinase (p38MAPK) blockers. Cell viability, proliferation, migration, mitochondrial membrane potential, mitochondrial oxygen consumption and oxidant/antioxidant system, were measured by specific assays. Western blot assay was used for the analysis of NO synthase (NOS) subtypes' and expression and activation of various kinases. In all experiments 17β‑estradiol was used for comparison. The results showed that phytoestrogens and estrogens can increase cell viability, proliferation/migration and improve mitochondrial membrane potential and oxygen consumption of H9C2. Furthermore, NO release was modulated by genistein and 17β‑estradiol. These effects were reduced or abolished by the pre‑treatment with ERs, GPER, Akt, ERK1/2 and p38MAPK blockers. Finally, a reduction of reactive oxygen species production and an increase of glutathione content was found in response to the two agents. In H9C2 cultured in physiological conditions, genistein induced endothelial NOS‑dependent NO production through the involvement of estrogenic receptors and by the modulation of intracellular signalling related to Akt, ERK1/2, and p38MAPK. Moreover, estrogens and phytoestrogens protected H9C2 against oxidative stress by reducing inducible NOS expression and through the modulation of the antioxidant system and mitochondrial functioning.

Glutathione as a mediator of cartilage oxidative stress resistance and resilience during aging and osteoarthritis

ABSTRACTPurpose: An underlying cause of osteoarthritis (OA) is the inability of chondrocytes to maintain homeostasis in response to changing stress conditions. The purpose of this article was to review and experimentally evaluate oxidative stress resistance and resilience concepts in cartilage using glutathione redox homeostasis as an example. This framework may help identify novel approaches for promoting chondrocyte homeostasis during aging and obesity.Materials and Methods: Changes in glutathione content and redox ratio were evaluated in three models of chondrocyte stress: (1) age- and tissue-specific changes in joint tissues of 10 and 30-month old F344BN rats, including ex vivo patella culture experiments to evaluate N-acetylcysteine dependent resistance to interleukin-1beta; (2) effect of different durations and patterns of cyclic compressive loading in bovine cartilage on glutathione stress resistance and resilience pathways; (3) time-dependent changes in GSH:GSSG in primary chondrocytes from wild-type and Sirt3 deficient mice challenged with the pro-oxidant menadione.Results: Glutathione was more abundant in cartilage than meniscus or infrapatellar fat pad, although cartilage was also more susceptible to age-related glutathione oxidation. Glutathione redox homeostasis was sensitive to the duration of compressive loading such that load-induced oxidation required unloaded periods to recover and increase total antioxidant capacity. Exposure to a pro-oxidant stress enhanced stress resistance by increasing glutathione content and GSH:GSSG ratio, especially in Sirt3 deficient cells. However, the rate of recovery, a marker of resilience, was delayed without Sirt3.Conclusions: OA-related models of cartilage stress reveal multiple mechanisms by which glutathione provides oxidative stress resistance and resilience.

Hypoglycemic and antioxidant activities of Clerodendrum inerme leaf extract on streptozotocin-induced diabetic models in mice

ObjectiveRecently, much attention has been paid to natural product-derived compounds for antidiabetic drug discovery. More recent studies are being focused on clarifying the bioactivity of plants and derived products. The aim of the present study was to investigate the anti-oxidant and antidiabetic activities of Clerodendrum inerme leaf extract (CILE) in streptozotocin-induced diabetic mice. MethodsC. inerme leaves were analyzed for preliminary phytochemical properties and the content of total phenolic and flavonoid were determined. In vitro anti-oxidant activity was measured using DPPH assay. Streptozotocin-induced diabetic model in mice was applied for in vivo study by the effect of CILE at two dose levels (343 and 686 mg/kg b.w.). ResultsThe results showed that C. inerme leaves contained the major constituents of flavonoids, alkaloids, tannins, triterpenes, and saponins. CILE exhibited the total polyphenol and flavonoid content with 120.458 mg gallic acid equivalent/g dry weight and 4.494 mg hispidulin equivalent/g dry weight, respectively. The anti-oxidant activity of CILE was expressed with IC50 = 25.28 µg/mL. CILE at the doses of 343 mg/kg and 686 mg/kg after 7 d administration exerted a decrease in plasma glucose, protected the liver, kidneys against oxidation stress via increasing glutathione content in the liver, and reduced malondialdehyde content in the liver and kidneys. Pancreatic histological analysis in diabetic mice treated with CILE also showed the pancreatic β-cells regeneration via increasing the size and number of pancreatic islets. ConclusionThese findings suggested that C. inerme leaves had potent antidiabetic and anti-oxidant activities. The results provide reliable scientific base, which is the premise for further research and development of CILE as supplements.

Lysine harvesting is an antioxidant strategy and triggers underground polyamine metabolism.

SummaryBoth single and multicellular organisms depend on anti-stress mechanisms that enable them to deal with sudden changes in the environment, including exposure to heat and oxidants. Central to the stress response are dynamic changes in metabolism, such as the transition from the glycolysis to the pentose phosphate pathway- a conserved first-line response to oxidative insults1,2. Here we report a second metabolic adaptation that protects microbial cells in stress situations. The role of the yeast polyamine transporter Tpo13–5 in maintaining oxidant resistance is unknown6. However, a proteomic time-course experiment suggests a link to lysine metabolism. We reveal a connection between polyamine and lysine metabolism during stress situations, in the form of a promiscuous enzymatic reaction in which the first enzyme of the polyamine pathway, Spe1p, decarboxylates lysine and forms an alternative polyamine, cadaverine. The reaction proceeds in the presence of extracellular lysine, which is taken up by cells to reach concentrations up to one hundred times higher than those required for growth. Such extensive harvest is not observed for the other amino acids, is dependent on the polyamine pathway and triggers a reprogramming of redox metabolism. As a result, NADPH- which would otherwise be required for lysine biosynthesis- is channelled into glutathione metabolism, leading to a large increase in glutathione concentrations, lower levels of reactive oxygen species and increased oxidant tolerance. Our results show that nutrient uptake occurs not only to enable cell growth, but when the nutrient availability is favourable it also enables cells to reconfigure their metabolism to preventatively mount stress protection.

Zinc-enriched probiotics enhanced growth performance, antioxidant status, immune function, gene expression, and morphological characteristics of Wistar rats raised under high ambient temperature.

The present study was conducted to evaluate the effects of zinc-enriched probiotics (ZnP) on growth performance, antioxidant status, immune function, related gene expression, and morphological characteristics of Wistar rats raised under high heat stress condition during summer. 36, 6-week-old male Wistar rats were randomly divided into three groups; fed with basal diet (control), basal diet with probiotics (P), and basal diet with zinc-enriched probiotics supplementation (ZnP, 100mg/L), for 40 consecutive days. Blood samples were collected through intracardiac method on the last day of experiment and tissues were collected from liver, heart, and kidneys. The results revealed that both P and ZnP significantly (P < 0.05) enhanced growth performance. However, ZnP remarkably increased glutathione content, glutathione peroxidase, and superoxide dismutase activities but reduced malondialdehyde level in serum of the Wistar rats. The concentration of IL-2, IL-6, and IFN-γ was significantly (P < 0.05) increased with treatments of P and ZnP compared to control group while IL-10 was significantly (P < 0.05) decreased. Additionally, the expression of SOD1, SOD2, MT1, and MT2 genes was significantly (P < 0.05) up-regulated with the treatment of ZnP, but Hsp90 and Hsp70 heat shock genes were significantly (P < 0.05) down-regulated with the treatment of P and ZnP, respectively. Hematoxylin and Eosin staining showed that both P and ZnP supplementation treatments induced changes in villus height and intestinal wall thickness. In conclusion, zinc-enriched probiotics supplementation can improve the growth performance of Wistar rats under high ambient temperature through enhancing antioxidant status, immune function, related genes expression, and intestinal morphological characteristics. This product may serves as a potential nutritive supplement for Wistar rats under high heat stress conditions.

Chronic treatment with C-type natriuretic peptide impacts differently in the aorta of normotensive and hypertensive rats.

The aim of this study was to determine whether exogenous administration of C-type natriuretic peptide (CNP) induces functional and morphological vascular changes in spontaneously hypertensive rats (SHR) compared with normotensive rats. Male 12-week-old normotensive Wistar and SHR were administered with saline (NaCl 0.9%) or CNP (0.75μg/h/100g) for 14days (subcutaneous micro-osmotic pumps). Systolic blood pressure (SBP) was measured in awake animals and renal parameters were evaluated. After decapitation, the aorta was removed, and vascular morphology, profibrotic markers, and vascular reactivity were measured. In addition, nitric oxide (NO) system and oxidative stress were evaluated. After 14-days of treatment, CNP effectively reduced SBP in SHR without changes in renal function. CNP attenuated vascular remodeling in hypertensive rats, diminishing both profibrotic and pro-inflammatory cytokines. Also, CNP activated the vascular NO system and exerted an antioxidant effect in aortic tissue of both groups, diminishing superoxide production and thiobarbituric acid-reactive substances, and increasing glutathione content. These results show that chronic treatment with CNP attenuates the vascular damage development in a model of essential hypertension, inducing changes in fibrotic, inflammatory, oxidative, and NO pathways that could contribute to beneficial long-term effects on vascular morphology, extracellular matrix composition, and function. The knowledge of these effects of CNP could lead to improved therapeutic strategies to not only control BP but also reduce vascular damage, primarily responsible for the risk of cardiovascular events.

Exogenous interference detection in urine proteinograms

Recently, much attention has been paid to natural product-derived compounds for antidiabetic drug discovery. More recent studies are being focused on clarifying the bioactivity of plants and derived products. The aim of the present study was to investigate the anti-oxidant and antidiabetic activities of Clerodendrum inerme leaf extract (CILE) in streptozotocin-induced diabetic mice.C. inerme leaves were analyzed for preliminary phytochemical properties and the content of total phenolic and flavonoid were determined. In vitro anti-oxidant activity was measured using DPPH assay. Streptozotocin-induced diabetic model in mice was applied for in vivo study by the effect of CILE at two dose levels (343 and 686 mg/kg b.w.).The results showed that C. inerme leaves contained the major constituents of flavonoids, alkaloids, tannins, triterpenes, and saponins. CILE exhibited the total polyphenol and flavonoid content with 120.458 mg gallic acid equivalent/g dry weight and 4.494 mg hispidulin equivalent/g dry weight, respectively. The anti-oxidant activity of CILE was expressed with IC50 = 25.28 µg/mL. CILE at the doses of 343 mg/kg and 686 mg/kg after 7 d administration exerted a decrease in plasma glucose, protected the liver, kidneys against oxidation stress via increasing glutathione content in the liver, and reduced malondialdehyde content in the liver and kidneys. Pancreatic histological analysis in diabetic mice treated with CILE also showed the pancreatic β-cells regeneration via increasing the size and number of pancreatic islets.These findings suggested that C. inerme leaves had potent antidiabetic and anti-oxidant activities. The results provide reliable scientific base, which is the premise for further research and development of CILE as supplements.

Role of salicylic acid and hydrogen sulfide in promoting lead stress tolerance and regulating free amino acid composition in Zea mays L.

Lead toxicity is a threat to growth and production of crop plants. In this study, effect of salicylic acid and sodium hydrosulfide pretreatments was investigated on the alteration in the Pb accumulation, protein content, nitrate reductase activity and metabolism of selected free amino acids in maize plants subjected to lead stress. Maize seeds were soaked in 0.5 mM salicylic acid and sodium hydrosulfide for 12 h and then exposed to 2.5 mM Pb (NO3)2 for 9 days. Results demonstrated that lead stress significantly reduced the plant growth, shoot glutathione content and protein content, nitrate reductase activity in the shoots and roots while increased glutathione content in roots of maize plants. We also observed accumulation of most free amino acids composition except tyrosine and tryptophan under lead stress condition. Plants pre-treated with salicylic acid and sodium hydrosulfide exhibited improvement of plant growth, decrease of Pb accumulation, increase of protein and glutathione contents and nitrate reductase activity. Salicylic acid and sodium hydrosulfide pretreatments decreased most amino acids content in shoot of lead stressed plants. In case of roots, salicylic acid and sodium hydrosulfide had different effects on the content of amino acids. Pretreatment of sodium hydrosulfide resulted in greater levels of free amino acids in roots. These results indicate that moderate lead stress can be attributed to effect of salicylic acid and sodium hydrosulfide by improvement of nitrate reductase activity and glutathione content and regulation of amino acids metabolism.

Comparing the protective effects of three sulfur compounds against acrylonitrile-induced acute toxicity in CYP2E1-induced rats

Cytochrome P450 2E1 (CYP2E1) can be induced by diabetes mellitus, nonalcoholic liver disease, and obesity. This study assessed the protective effects of three sulfur compounds, namely phenethyl isothiocyanate (PEITC), dimethyl trisulfide (DMTS), and sodium thiosulfate (STS), on acrylonitrile (ACN)-induced acute toxicity in rats enriched with CYP2E1. PEITC and DMTS were administered intragastrically (i.g.), whereas STS was injected intraperitoneally (i.p.) at an identical dose of 0.5 mmol/kg for 3 days in acetone-pretreated rats before ACN (90 mg/kg) injection (i.p.). Acetone-treated rats that expressed high levels of CYP2E1 were more susceptible to ACN-induced acute toxicity. The sulfur compounds reduced the rate of convulsions and loss of the righting reflex in acute ACN-exposed CYP2E1-induced rats; PEITC and DMTS also increased the survival rates. PEITC inhibited hepatic CYP2E1 activity and protected hepatic and cerebral cytochrome c oxidase (CcOx) activities in acute ACN-exposed CYP2E1-enriched rats; DMTS protected hepatic CcOx activity. DMTS attenuated ACN-induced oxidative injury by reducing malondialdehyde (MDA) levels and increasing glutathione content in the brain. STS only reduced cerebral MDA levels, whereas PEITC did not exhibit any antioxidant effects. Collectively, PEITC provided superior protective effects against ACN-induced acute toxicity in rats with increased CYP2E1 activity, followed by DMTS; STS provided limited effects. PEITC and DMTS might be considered as promising chemopreventive agents against ACN-induced acute toxicity in vulnerable subpopulations with increased CYP2E1 activity.