Glutathione Reductase (GR) And Glutathione Peroxidase Research Articles

Effects of two typical quinolone antibiotics in the marine environment on Skeletonema costatum

This study investigated the effects of levofloxacin (LEV) and norfloxacin (NOR) on Skeletonema costatum, focusing on cell growth, chlorophyll a (Chla) content, maximal quantum yield of PSII (Fv/Fm), protein content, enzyme activities of superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GSH-PX), and the membrane lipid peroxidation product malondialdehyde (MDA) content were conducted to analyze the responses of S. costatum under LEV and NOR exposure. Cell growth, Chla content, Fv/Fm, protein content, enzyme activities, and MDA content were assessed to elucidate physiological changes. Both LEV and NOR inhibited S. costatum growth, except for 10 mg/L NOR, which promoted growth. Algal cells exhibited higher sensitivity to LEV, with 96h-IC50 values of 14.770 mg/L for LEV and 44.250 mg/L for NOR. Low NOR concentration (10 mg/L) increased Chla content, while high antibiotic concentrations (>20 mg/L for LEV, >100 mg/L for NOR) decreased Chla content and Fv/Fm, indicating an impact on photosynthesis. Elevated LEV and NOR levels reduced protein and MDA content but increased GR, SOD, and GSH activities, indicating induced oxidative stress. The study provides a comprehensive analysis of LEV and NOR effects on marine microalgae growth and underlying physiological mechanisms, shedding light on potential ecological risks posed by antibiotics in marine ecosystems.

Pomelo polysaccharide extract inhibits oxidative stress, inflammation, and mitochondrial apoptosis of Epinephelus coioides

Although the production of pomelo, a citrus fruit, has recently increased considerably in China, the therapeutic potential of the fruitlets on aquatic animals has not been widely studied. Thus, in this study, we aimed to evaluate the protective effects of the crude polysaccharide extracted and purified from pomelo fruitlet (YZW-A), on oxidative stress, inflammation, and mitochondrial dysfunction-mediated apoptosis. For this, we added YZW-A (0, 100, 200 and 400 μg/mL) to Epinephelus coioides spleen (GS) cells before incubation with 0.8 mM of H2O2. Morphological indices showed significant deterioration when exposed to H2O2 (P < 0.05), whereas this was did not observed in the cells exposed to YZW-A. Administration of YZW-A (100 and 200 μg/mL) substantially mitigated the H2O2-induced oxidative stress, as shown by the elevated activities of the mitochondrial respiratory complexes and antioxidative enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) (P < 0.05). NF-κB derived inflammation was also significantly attenuated by the diminished gene expression of the NF-κB regulated proinflammatory cytokines (TNF-α, IL-β and IL-6) (P < 0.05). In addition, apoptosis-related indicators (Bax, Bcl-2, and caspase-3, −8, and − 9) and the cell apoptosis rate showed that mitochondrial dysfunction-mediated apoptosis was alleviated due to the decreased oxidative stress. Pretreatment with the NF-κB inhibitor, BAY11–7082 (20 μM), dramatically reduced the expression of the downstream genes of NF-κB, including the proinflammatory genes, IL-β and IL-6 (P < 0.05), and the proapoptotic genes, Bax, caspase 3, and caspase 9 (P < 0.05), which confirmed that the NF-κB signaling pathway is involved in the mechanisms of inflammation and apoptosis. In support of the results in vitro study, we further added YZW-A at the doses of 0, 200, 400, 800 and 1600 mg/kg in the diet for 56 days prior to the treatment of H2O2 or saline. The results demonstrated that administration of YZW-A significantly ameliorated H2O2-induced liver injury as evident by the decline of Serum albumin (ALB), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), and cholinesterase (CHE) content in the groupers. Furthermore, the changes on the activities of the antioxidative enzymes and the mRNA expression of the apoptosis-related indicators and the proinflammatory cytokines corresponded well with that of in GS cells. In addition, YZW-A treatment repressed the enhancement of enzymic activities of the proinflammatory cytokines induced by H2O2. In summary, these findings showed the therapeutic potential of YZW-A on H2O2-induced oxidative stress, and further mitigated the NF-κB regulated inflammation and apoptosis.

Lactobacillus delbrueckii Protected Intestinal Integrity, Alleviated Intestinal Oxidative Damage, and Activated Toll-Like Receptor-Bruton's Tyrosine Kinase-Nuclear Factor Erythroid 2-Related Factor 2 Pathway in Weaned Piglets Challenged with Lipopolysaccharide.

Oxidative stress is increasingly being recognized as a player in the pathogenesis of intestinal pathologies, and probiotics are becoming an attractive means of addressing it. The present study investigated the effects of dietary supplementation with Lactobacillus delbrueckii (LAB) on intestinal integrity and oxidative damage in lipopolysaccharide (LPS)-challenged piglets. A total of 36 crossbred weaned piglets (Duroc × Landrace × Large Yorkshire) were randomly divided into three groups: (1) non-challenged controls (CON), (2) LPS-challenged controls (LPS), and (3) 0.2% LAB (2.01 × 1010 CFU/g) + LPS treatment (LAB + LPS). On the 29th day of the experiment, the LPS and CON groups were injected intraperitoneally with LPS and saline at 100 ug/kg body weight, respectively. The results show that the LPS-induced elevation of the serum diamine oxidase (DAO) level and small intestinal crypt depth (CD) were reversed by the dietary addition of LAB, which also markedly increased the ileal expression of tight junction proteins (occludin, ZO-1, and claudin-1) in the LPS-challenged piglets. Furthermore, LAB supplementation normalized other LPS-induced changes, such as by decreasing malondialdehyde (MDA) in both the serum and intestinal mucosa and 8-hydroxy-2-deoxyguanosine (8-OHdG) in the jejunal mucosa, increasing glutathione reductase (GR) and glutathione peroxidase (GSH-Px) in both the serum and intestinal mucosa, and increasing glutathione (GSH) and superoxide dismutase (SOD) in the jejunal mucosa. LAB also activated Toll-like receptor (TLR)–Bruton’s tyrosine kinase (Btk)–nuclear factor erythroid 2-related factor 2(Nrf2) signaling pathways in the intestine, suggesting that it plays a vital role in the ameliorative antioxidant capacity of weaned piglets. In summary, LAB increased intestinal integrity by improving the intestinal structure and tight junctions while enhancing antioxidant functions via the activation of the TLR–Btk–Nrf2 signaling pathway.

Epigallocatechin-3-gallate Alleviates Vanadium-Induced Reduction of Antioxidant Capacity via Keap1-Nrf2-sMaf Pathway in the Liver, Kidney, and Ovary of Laying Hens.

This study evaluated the effect of epigallocatechin-3-gallate (EGCG) alleviating the reduction of antioxidant capacity induced by dietary vanadium (V) in the liver, kidney, and ovary of laying hens. Furthermore, Kelch-like ECH-associated protein 1(Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-small Maf proteins (sMaf) pathway was explored to reveal the molecular mechanism. A total of 768 40-week-old Hyline-Brown laying hens were randomly allocated to 4 groups with 8 pens per group and 24 hens per pen. The experimental groups were as follows: control (basal diet); V15, control + 15 mg/kg V; EGCG150, control + 150 mg/kg EGCG; V15 + EGCG150, V15 + 150 mg/kg EGCG. Our results revealed that dietary EGCG supplementation completely alleviated the V-induced reductions of hen-day egg production, average egg weight, Haugh unit, albumen height, eggshell strength, and eggshell thickness. Dietary EGCG supplementation completely prevented the V-induced reductions of serum follicle-stimulating hormone and luteinizing hormone levels. Besides, dietary EGCG supplementation reversed the V-induced increments of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA). In addition, dietary EGCG supplementation partially alleviated the V-induced reductions of the enzyme activities and gene expressions of superoxidative dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GSH-Px). Furthermore, dietary EGCG supplementation partially alleviated the V-induced reductions of Nrf2 and sMaf gene expressions, and the increments of Keap1 gene expression. In summary, EGCG partially alleviated V-induced reduction of antioxidant capacity through Keap1-Nrf2-sMaf pathway in the liver, kidney, and ovary of laying hens.

Evaluation of Anticancer Activity of Satureja montana Supercritical and Spray-Dried Extracts on Ehrlich's Ascites Carcinoma Bearing Mice.

Satureja montana herbal species belongs to aromatic medicinal plants with a significant place in traditional medicine. However, products produced with conventional procedures do not meet the requirements of the modern market which include environmentally-safe processes that provide quality, safe, and standardized products. In this study, the antiproliferative activity of S. montana extracts obtained by supercritical carbon dioxide and solid–liquid extraction followed by spray drying was investigated using the in vivo model of Ehrlich ascites carcinoma (EAC) in mice. The impact of two concentrations of extracts on the growth of tumor and the redox status of malignant cells was monitored. It was determined that the extracts induced oxidative stress in the malignant cells which was confirmed by the changes in activity of biochemical indicators of oxidative stress. The posttreatment was not an efficient approach, while the extracts applied as pretreatment and treatment resulted in an increase in the xanthine oxidase (XOD) activity, a decrease in catalase (CAT) activity, and an increase in the intensity of lipid peroxidation (LPx). Furthermore, a decrease in the values of reduced glutathione (GSH) and an increase in glutathione reductase (GR) and glutathione peroxidase (GSHPx) in EAC cells were recorded.

New insights into cadmium stressful-conditions: Role of ethylene on selenium-mediated antioxidant enzymes

Cadmium (Cd) contamination has generated an environmental problem worldwide, leading to harmful effects on human health and damages to plant metabolism. Selenium (Se) is non essential for plants, however it can improve plant growth and reduce the adverse effects of abiotic stress. In addition, ethylene may interplay the positive effects of Se in plants. In order to investigate the role of ethylene in Se-modulation of antioxidant defence system in response to Cd-stress, we tested the hormonal mutant Epinastic (epi) with a subset of constitutive activation of the ethylene response and Micro-Tom (MT) plants. For this purpose, Se mineral uptake, Cd and Se concentrations, pigments, malondialdeyde (MDA) and hydrogen peroxide (H2O2) contents, ethylene production, glutathione (GSH) compound, and superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) activities were analysed in MT and epi plants submitted to 0.5 mM CdCl2 and 1 μM of selenate or selenite. MT plants treated with both Se forms increased growth in the presence or not of 0.5 mM CdCl2, but not change epi growth. Both Se forms reduced Cd uptake in MT plants and cause reverse effect in epi plants. P, Mg, S, K and Zn uptake increased in epi plants with Se application, irrespective to Cd exposure. Chlorophylls and carotenoids contents decreased in both genotypes under Cd exposure, in contrast to what was observed in epi leaves in the presence of Se. When antioxidant enzymes activities were concerned, Se application increased Mn-SOD, Fe-SOD and APX activities. In the presence of Cd, MT and epi plants exhibited decreased SOD activity and increased CAT, APX and GR activities. MT and epi plants with Se supply exhibited increased APX and GR activities in the presence of Cd. Overall, these results suggest that ethylene may be involved in Se induced-defence responses, that triggers a positive response of the antioxidant system and improve growth under Cd stress. These results showed integrative roles of ethylene and Se in regulating the cell responses to stressful-conditions and, the cross-tolerance to stress could be used to manipulate ethylene regulated gene expression to induce heavy metal tolerance.

Physiological Responses and Tolerance Evaluation of Five Poplar Varieties to Waterlogging

Waterlogging resistance of five poplar varieties, ‘Danhongyang’ (DHY), ‘Juba-261’ (JB-261), ‘Zongqiansanhao’ (ZQ-3), ‘Zhonglin-2025’ (ZL-2025), and ‘Nanlin-895’ (NL-895), was evaluated under the simulated waterlogging conditions. Data on changes in leaf color and morphology as well as in biochemical indices, such as chlorophyll, malonaldehyde, soluble protein, soluble sugar content, superoxide dismutase (SOD), peroxidases (POD), ascorbate peroxidase (APX), glutathione reductase (GR), and glutathione peroxidase (GSH-PX) activities, relevant to submergence stress, were analyzed. The principal component analysis of the data identified the waterlogging resistance coefficient of the indices, which showed that waterflooding brought about different degrees of damage in the five poplar varieties, with DHY having the lowest waterlogging index. The leaf pigment content of the poplar was remarkably decreased by waterlogging, whereas malondialdehyde (MDA) and proline contents were enhanced, but in different extents among the poplar varieties. Nearly all other poplar varieties showed a tendency of decline in JB-261, ZQ-3, ZL-2025, NL-895, except for SOD activity in DHY, which increased under submergence stress. Poplar varieties had varying degree of changes in POD activity, and APX activity tended to increase upon waterlogging. GR also displayed increasing tendency in JB-261, ZL-2025 and NL-895, except for in ZQ-3, which declined under waterlogging stress. GSH-PX except for ZQ-3 displayed no significant change, which showed a tendency of decline in DHY, JB-261, ZL-2025, and NL895. Principal component analysis allowed us to reduce16 indices to four independent indices. The subordinate function analysis identified that the DHY variety had the highest waterlogging tolerance, whereas the NL-895 variety had the lowest waterlogging tolerance among tested varieties.&#x0D; &#x0D; *********&#x0D; In press - Online First. Article has been peer reviewed, accepted for publication and published online without pagination. It will receive pagination when the issue will be ready for publishing as a complete number (Volume 47, Issue 3, 2019). The article is searchable and citable by Digital Object Identifier (DOI). DOI link will become active after the article will be included in the complete issue.&#x0D; *********

Effect of mercury chloride on oxidative stress and nuclear factor erythroid 2-related factor 2 signalling molecule in liver and kidney of laying hens.

This study investigated the effects of mercury chloride (HgCl2 ) on the deposition of mercury (Hg), histopathology and oxidative stress in liver and kidney of laying hens. The gene expressions of antioxidant enzymes and nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) were further studied to uncover the molecular mechanism. A total of 960 40-week-old Hyline brown laying hens were randomly allocated to five treatments with eight pens per treatment and 24hens per pen. The hens were fed with five experimental diets containing graded levels of Hg at 0.270, 1.250, 3.315, 9.405 and 27.230mg/kg respectively. Results revealed that both deposition of Hg and score of injury in liver and kidney were significantly increased as dietary Hg dosage up to 27.230mg/kg diet. Deposition of Hg was positively related to score of injury in liver and kidney of laying hens. Besides, the activities of superoxidative dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px), and glutathione (GSH) content all significantly decreased (p<0.05), while malondialdehyde (MDA) content significantly increased (p<0.05) after Hg exposure in liver and kidney of laying hens. In addition, positive relationships occurred between antioxidant enzyme activities and antioxidant enzyme gene expressions except between SOD activity and manganese superoxide dismutase (MnSOD) gene expression in liver. Meanwhile, Nrf2 gene expression was positively related to antioxidant gene expressions and negatively connected with Keap1 gene expression. Negative relationships occurred between Nrf2 and Keap1 protein levels in liver and kidney. In conclusion, Hg could dose-dependently damage liver and kidney and induced hepatic and renal oxidative stress by means of suppressing Nrf2-Keap1 signalling molecule in laying hens.

Fructose 1, 6-diphosphate prevents alcohol-induced liver injury through inhibiting oxidative stress and promoting alcohol metabolism in mice

Fructose 1, 6-diphosphate (FDP), a glycolytic intermediate，has been identified to possess antioxidant activities. Here we show the protective effect of FDP against alcohol-induced liver injury in mice and the underlying mechanisms. The in vivo experiments demonstrated that FDP, orally administered to mice, dose-dependently suppressed alcohol (50%, v/v, 12ml/kg)-induced increase of serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), serum triglyceride (TG) level and hepatic malondialdehyde (MDA) level. FDP also inhibited liver histological lesions induced by seven-day administration of alcohol to mice. In vitro study indicated that FDP inhibited ethanol-induced L02 cell apoptosis via reducing pro-caspase3 protein level and increasing poly ADP-ribose polymerase (PARP) cleavage. The mechanism analysis showed that FDP prevented ethanol-induced decrease of mouse antioxidant capability through inhibiting the reducion of the level of glutathione (GSH) and activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-PX) in mouse livers, and suppressing the reducion of GSH level and SOD activity in L02 cells. FDP also enhanced alcohol metabolic rate through increasing alcohol dehydrogenase (ADH) activity and acetaldehyde dehydrogenase (ALDH) protein level, and down-regulating cytochrome p450 2E1 (CYP2E1). These results displayed that FDP protected mice from alcohol-induced liver injury, suggesting the potential activity of FDP in preventing alcoholic liver disease (ALD).

D-limonene ameliorates diabetes and its complications in streptozotocin-induced diabetic rats

It is known that diabetes causes some complications including alterations in lipid profile, hepatic enzyme levels but also it causes oxidative stress. Limonene, a major component of Citrus oils, has important health beneficial effects in lowering the level of oxidative stress due to its antioxidant activity. The aim of this study was to investigate the effects of D-limonene on streptozotocin (STZ)-induced diabetes in Wistar albino rats. For this purpose, DNA damage was evaluated by alkaline comet assay. Changes in the activities of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GSHPx) and the levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG), total glutathione (GSH), malondialdehyde (MDA), insulin, total bilirubin and BCA protein, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT), high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol and triglyceride were also evaluated. D-limonene treatment was found to significantly decrease DNA damage, GR enzyme activities and MDA levels and significantly increase GSH levels and CAT, SOD and GSH-Px enzyme activities and altered lipid and liver enzyme parameters in diabetic rats. According to our results, it seems that D-limonene might have a role in the prevention of the complication of diabetes in rats.

Histopathological findings of renal tissue induced by oxidative stress due to different concentrations of fluoride.

It has been reported that excessive intake of fluoride can induce renal lesions. However, its pathogenesis is still less understood. Therefore, this study was conducted to investigate oxidative damage and the relationships between the oxidative damage and renal lesions in fluoride-treated mice by using the methods of histopathology, biochemistry, flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). A total of 240 ICR mice were randomly divided into four equal groups (sodium fluoride was given orally at the dose of 0, 12, 24 and 48 mg/kg body weight for 42 days, respectively). We found that fluoride in excess of 12 mg/kg induced renal oxidative damage, which was characterized by increasing the levels of reactive oxygen species (ROS) production and contents of malondialdehyde (MDA) and protein carbonyls (PC), and decreasing the abilities of anti-superoxide anion (ASA) and anti-hydroxyl radical (AHR), glutathione (GSH) content, as well as activities and mRNA expression levels of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px). Concurrently, fluoride caused degeneration and necrosis of the tubular cells, renal tubular hyaline casts and glomeruli swelling, which were consistent with the alteration of renal function parameters including elevated contents of serum creatinine (Cr), serum uric acid (UA), blood urea nitrogen (BUN), and the activities of urinary N-acetyl-b-D-glucosaminidase (NAG), renal lactate dehydrogenase (LDH), and reduced activities of sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) and acid phosphatase (ACP) in the kidney. The above-mentioned results showed that fluoride in excess of 12 mg/kg induced renal oxidative damage, which then caused renal lesions and dysfunctions. These findings also clearly demonstrated that oxidative damage is one of the mechanisms of fluoride-induced renal lesions and dysfunctions.

Phenolic Profile, Antiradical and Antitumour Evaluation of Raspberries Pomace Extract from Serbia.

Raspberry waste, obtained from two cultivars, Meeker (ERM) and Willamette (ERW) was subjected to evaluation antioxidants and antitumour activities as a potential source of phenolics. Some phenolic acids and flavonoids were identified and quantified by HPLC. Antioxidant activity was tested by measuring ability to scavenge DPPH• and •OH by ESR spectroscopy. IC50DPPH• varied from 0.67 for ERM to 0.54 mg/mL for ERW, while IC50•OH values varied from 3.73 for ERM to 1.23 mg/mL for ERW. Cytotoxic activity was investigated using in vivo model of Ehrlich Ascite carcinoma cells (EAC) in mice. Pretreatment with extracts exhibited potent cytotoxic activity against EAC cells (up to 60%) and both extracts inhibited the tumour growth. Activity of xanthine oxidase (XOD) was extremely increased in pretreated animals, while the activity of enzyme complex glutathione reductase (GR) and glutathione peroxidase (GSHPx) was significantly increased. This study suggests that raspberry pomace could be used as nutraceutic resource and functional food ingredient.

Effects of antioxidant system on coronary artery lesions in patients with abnormal glucose metabolism.

To evaluate the effects of catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) system on the range and severity of coronary artery lesions in patients with abnormal glucose metabolism. This study included 766 patients with abnormal glucose metabolism. Levels of fasting blood lipids, blood glucose, CAT, SOD, GSH, glutathione reductase (GR), and glutathione peroxidase (GSH-Px) were measured in all the patients. Coronarography was performed, and the degree of the lesions in each coronary artery was quantitatively analyzed using the Gensini scoring system. In patients with impaired glucose regulation and diabetes, the number of coronary artery branches with stenosis and the Gensini scores were inversely correlated with the plasma levels of CAT, SOD, GSH, GH, and GSH-Px (P<0.001). Patients were grouped according to the Gensini scores. As the scores increased, the levels of CAT, SOD, GSH, GSH-Px, and GR gradually decreased. Logistic gradual regression analysis showed that GSH-Px and CAT were independent risk factors associated with the coronary artery lesions in three or more branches. Decreased plasma levels of CAT, SOD, GSH, GR, and GSH-Px were inversely correlated, at least to some extent, with the extent of coronary artery lesions. Particularly, GSH-Px and CAT were independent risk factors associated with coronary artery lesions involving three or more branches. This suggests that long-term hyperglycemia leads to enhancement of oxidative stress.

Hepatoprotective constituents of Firmiana simplex stem bark against ethanol insult to primary rat hepatocytes.

Background:Ethanol causes hepatic cellular damage by alterations in biological functions. This study evaluated the hepatoprotective potential of the methanolic extract originating from Firmiana simplex (Sterculiaceae) stem bark against the ethanol-induced hepatotoxicity in rat primary hepatocytes.Materials and Methods:The extract of F. simplex stem bark was successively fractionated into n-hexane, chloroform, ethyl acetate (EtOAc), and n-butanol. Column chromatography with silica gel and sephadex LH-20 was used to isolate the EtOAc fraction. Rat primary hepatocytes were cultured to study the hepatoprotective activity of isolated substances against ethanol-induced toxicity. Intracellular reactive oxygen species (ROS) levels, the antioxidant activities of glutathione reductase (GR) and glutathione peroxidase (GSH-PX) enzymes, and the GSH content were measured to examine the antioxidative property of the isolated compounds.Results:Two flavonoid glycosides, quercitrin (1) and tamarixetin 3-O-rhamnopyranoside (2), were isolated from the active EtOAc fraction. Compound 1 significantly protected rat primary hepatocytes against ethanol-induced oxidative stress by reducing the intracellular ROS level and preserving antioxidative defense systems such as GR, GSH-PX, and total GSH.Conclusion:This is the first report on the hepatoprotective activities of the extract of F. simplex. The EtOAc fraction of F. simplex stem bark and its major constituent quercitrin (1) could function as hepatoprotective agents to attenuate the development of alcoholic liver disease.

Protective effect of tea polyphenols on renal ischemia/reperfusion injury via suppressing the activation of TLR4/NF-κB p65 signal pathway

Tea polyphenols (TP) was investigated in rats for its protective effect on renal ischemia/reperfusion injury (RIRI). Rats were randomized into groups as follows: (I) sham group (n=10); (II) RIRI group (n=10); (III) RIRI+TP (100mg/kg) group (n=5); (IV) RIRI+TP (200mg/kg) group (n=5); (V) RIRI+TP+ Astragalus mongholicus aqueous extract (AMAE) (300 mg/kg+100mg/kg) group (n=5). For the IRI+TP groups, rats were orally given with tea polyphenols (100, 200 and 300 mg/kg body weight) once daily 10 days before induction of ischemia, followed by renal IRI. For the sham group and RIRI group, rats were orally given with equal volume of saline once daily 10 days before induction of ischemia, followed by renal IRI. Results showed that tea polyphenol pretreatment significantly suppressed ROS level and MDA release. On the other hand, in rats subjected to ischemia-reperfusion, the activities of endogenous antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) showed recovery, whereas the levels of urea nitrogen and serum creatinine were reduced by administration of tea polyphenols orally for 10 days prior to ischemia-reperfusion. Moreover, tea polyphenol pretreatment significantly decreased TLR4 and NF-κB p65 protein expression levels in RIRI rats. At the same time, tea polyphenol pretreatment attenuated the increased level of serum IL-1β, IL-6, ICAM-1 and TNF-α, and enhanced IL-10 production in RIRI rats. Furthermore, tea polyphenol pretreatment significantly decreased renal epithelial tubular cell apoptosis induced by renal ischemia/reperfusion, alleviating renal ischemia/reperfusion injury. These results cumulatively indicate that tea polyphenol pretreatment could suppress the TLR4/NF-κB p65 signaling pathway, protecting renal tubular epithelial cells against ischemia/reperfusion-induced apoptosis, which implies that antioxidants may be a potential and effective agent for prevention of the ischemic/reperfusion injury through the suppression extrinsic apoptotic signal pathway induced by TLR4/NF-κB p65 signal pathway. Moreover, supplement of AMAE can increased renal protection effect of TP.

Schisandra Chinensis Baillon regulates the gene expression of phase II antioxidant/detoxifying enzymes in hepatic damage induced rats.

BACKGROUND/OBJECTIVESThis study investigated the antioxidant activities and hepatoprotective effects of Schisandra chinensis Baillon extract (SCE) against tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatic damage in rats.MATERIALS/METHODSSprague-Dawley (SD) rats were pretreated with SCE (300, 600, and 1,200 mg/kg BW) or saline once daily for 14 consecutive days. On day 14, each animal, except those belonging to the normal control group, were injected with t-BHP (0.8 mmol/kg BW/i.p.), and all of the rats were sacrificed 16 h after t-BHP injection.RESULTSAlthough no significant differences in AST and ALT levels were observed among the TC and SCE groups, the high-dose SCE group showed a decreasing tendency compared to the TC group. However, erythrocyte SOD activity showed a significant increase in the low-dose SCE group compared with the TC group. On the other hand, no significant differences in hepatic total glutathione (GSH) level, glutathione reductase (GR), and glutathione peroxidase (GSH-Px) activities were observed among the TC and SCE groups. Hepatic histopathological evaluation revealed that pretreatment with SCE resulted in reduced t-BHP-induced incidence of lesions, such as neutrophil infiltration, swelling of liver cells, and necrosis. In particular, treatment with a high dose of SCE resulted in induction of phase II antioxidant/detoxifying enzyme expression, such as glutathione S-transferase (GST) and glutamate-cysteine ligase catalytic subunit (GCLC).CONCLUSIONSBased on these results, we conclude that SCE exerts protective effects against t-BHP induced oxidative hepatic damage through the reduction of neutrophil infiltration, swelling of liver cells, and necrosis. In addition, SCE regulates the gene expression of phase II antioxidant/detoxifying enzymes independent of hepatic antioxidant enzyme activity.

English

The aim of the present study is to investigate the effect of rutin, a potent antioxidant and anti-inflammatory compound on experimentally-induced diabetic neuropathy (DN) in male Wistar rats. In diabetic and normal rats, the pain-related behavior tests were performed before and after rutin (50 and 100 mg/kg/day for 6 weeks) treatments. In serum, fasting glucose, insulin, tumor necrosis factor-&alpha; (TNF-&alpha;), interleukin-6 (IL-6) and interleukin-1&beta; (IL-1&beta;) levels were estimated and in sciatic nerve, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels, and superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione-reductase (GR) and glutathione peroxidase (GSH-Px) activities were measured. Diabetic rats developed neuropathy which was apparent from decreased tail-flick and paw-withdrawal latencies and by following decrease in performance on Rota-Rod treadmill. Rutin treatments ameliorated the hyperalgesia, analgesia and improved motor coordination. Streptozotocin (STZ) significantly increased TBARS and decreased GSH levels in sciatic nerve where rutin treatment significantly protected those changes. In diabetic rats, SOD, CAT, GST, GSH-Px and GR activities were significantly inhibited. Rutin treatment significantly ameliorated decrease in antioxidant defense. Present results demonstrate protective effect of rutin in diabetic neuropathy through attenuation of oxidative stress and they suggest that rutin is a potential drug for the prevention of early diabetic-induced neuropathy. Key words: Streptozotocin, rutin, oxidative stress, neuropathy, diabetes.

Neuroprotective Effect of Thymoquinone on Repeated Immobilization Stress-Induced Oxidative Stress in Rats

The present study was designed to investigate the effect of Thymoquinone (TQ) in restraint stress- induced biochemical alterations in Wistar albino rats. Restraint stress was applied for 21 days (4 h/day) and 60 min before every stress exposure the rats were treated with two doses of TQ (5 and 10 mg/kg). In serum, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Interleukin-1β (IL-1β) Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) were estimated. Thiobarbituric Acid Reactive Substances (TBARS), reduced Glutathione (GSH), nitrite and nitrate levels and Super Oxide Dismutase (SOD), Catalase (CAT), Glutathione-S-Transferase (GST), Glutathione-Reductase (GR) and Glutathione Peroxidase (GSH-Px) activities were estimated in brain. Interleukins and enzymatic activities in serum significantly elevated by the restraint stress and were ameliorated by both the doses of TQ treatment. In brain TBARS, nitrite and nitrate levels significantly elevated due to restraint stress, the TQ treatment brings back to normal levels. Restraint stress significantly decreased in oxidative enzyme activities as the SOD, CAT, GST, GSH-Px and GR. TQ treatments significantly enhanced the activities compared to untreated stressed rats. Present results revealed that, TQ reduced the restraint stress-induced oxidative process in terms of above mentioned biochemical parameters. Thus, in view of its antioxidative nature, TQ may be developed as an effective therapeutic agent for stress-induced oxidation and CNS depression.

Neuroprotective Effect of Silymarin by Modulation of Endogenous Biomarkers in Streptozotocin Induced Painful Diabetic Neuropathy

Aim of the present study is to investigate the effect of silymarin (SM), a potent antioxidant and anti-inflammatory compound on experimentally-induced Diabetic Neuropathy (DN) in male Wistar rats. Diabetes was induced by single streptozotocin (STZ) injection in rats. Pain-related behavior tests were performed including tail flick, paw-pressure analgesia and Rota-rod performance. Silymarin treatment was started after 21st day of diabetes induction and continued for 6 consecutive weeks. In serum fasting glucose, insulin, tumor necrosis factor-&alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1&beta (IL-1&beta) levels were estimated and in sciatic nerve, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), Superoxide Dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST), glutathione-reductase (GR) and glutathione peroxidase (GSH-Px) activities were measured. Diabetic rats developed neuropathy which was apparent from decreased tail-flick latency and paw-withdrawal latency.This was escorted by decreased motor coordination as assessed by performance on Rota-rod treadmill. Treatment with SM ameliorated the hyperalgesia, analgesia and improved motor coordination. STZ significantly increased TBARS and decreased GSH levels in sciatic nerve where silymarin treatment significantly protected those changes. Enzymatic activities such as SOD, CAT, GST, GSH-Px and GR were significantly inhibited in sciatic nerve of diabetic rats. The SM treatment significantly ameliorated decrease in antioxidant defense. Our results clearly demonstrate protective effect of SM is mediated through attenuation of oxidative stress and suggest therapeutic potential of SM in attenuation of diabetic neuropathy.

Vitamin D status and its association with antioxidant profiles in diabetic patients: A cross-sectional study in Iran

There are increasing evidences about the relationship between vitamin D status and the control of diabetes. Several studies showed that vitamin D has an antioxidant property. In this study, we aimed to determine the relationship between serum levels of 25-hydroxy vitamin D (25-OH-D) and glycemic, antioxidant profile in diabetes compared to healthy groups. This cross-sectional study was conducted in 100 patients with type 2 diabetes mellitus (T2DM) and 100 healthy controls. Fasting serum levels of 25-OH-D, calcium, phosphorous, parathyroid hormone, glucose, HbA(1C), insulin, homeostasis model assessment of insulin resistance index, total antioxidant capacity (TAC), activities of superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GSH-PX) were measured. Eighty-two percent of type 2 diabetic patients and 75% of healthy subjects were suffering from vitamin D deficiency or insufficiency. The activities of GR and GSH-PX were higher in diabetic patients compared to control. There was a negative relationship between 25-OH-D and activity of GR, GSH-PX. Also, 25-OH-D had a positive association with activity of SOD in diabetic patients. In the control group, 25-OH-D had an inverse relationship with SOD, GSH-PX, and positively with GR activities. Vitamin D deficiency has a high prevalence among Iranian adult population with and without type 2 diabetes. Our results showed that vitamin D may have a beneficial effect on the control of glycemic profiles and oxidative stress in T2DM patients.