Hepatic Glutathione Reductase Research Articles

Dietary Thymol Supplementation Promotes Antioxidant Responses and Thermal Stress Resistance in Rainbow Trout, Oncorhynchus mykiss.

Rainbow trout fingerlings were fed, in triplicate, diets supplemented with 0 (CTL), 50 (50 TM), 100 (100 TM), 200 (200 TM), 400 (400 TM) and 800 (800 TM) mg/kg of thymol, followed by 48 h of thermal stress. Growth performance and humoral immunological parameters showed no significant responses to dietary thymol concentrations. Fish fed 50-400 mg/kg thymol diets had significantly higher survival after heat stress. Plasma cortisol, glucose, hepatic glutathione peroxidase, glutathione reductase and erythrocyte catalase significantly increased after thermal stress, whereas total plasma antioxidant capacity, ascorbate, and hepatic/erythrocyte reduced-glutathione significantly decreased. There were significant elevations in plasma ascorbate and hepatic glutathione reductase in the 50 TM, 100 TM and 200 TM groups; plasma total antioxidant capacity in the 100 TM and 200 TM groups; hepatic glutathione peroxidase in the 200 TM group; and hepatic-reduced glutathione in the 100 TM, 200 TM and 400 TM groups, compared to CTL. The highest hepatic superoxide dismutase and lowest hepatic malondialdehyde were observed in the 100 TM group before heat stress. These parameters significantly increased after thermal stress in the treatment groups, except in the 100 TM and 200 TM groups. Hepatic catalase showed no significant difference among the treatment groups before thermal stress. Hepatic catalase significantly increased after heat stress in all treatment groups, except in the 100 TM group. Erythrocyte superoxide dismutase significantly increased in the 100 TM group before heat stress, whereas erythrocyte malondialdehyde significantly decreased in the 100 TM and 200 TM groups after thermal stress. Based on the results, 100 mg/kg of thymol can promote antioxidant power and thermal stress resistance in rainbow trout.

Ameliorating the impairment of glucose utilization in a high-fat diet-induced obesity model through the consumption of Tucum-do-Cerrado (Bactris Setosa Mart.).

We evaluated the effect of Tucum-do-Cerrado on glucose metabolism homeostasis and its relationship with redox-inflammatory responses in a high-fat (HF) diet-induced obesity model. The HF diet increased energy intake, feed efficiency, body weight, muscle and hepatic glycogen, insulin, homeostatic model assessment of insulin resistance (HOMA IR) and beta (β)-cell function, and gut catalase (CAT) activity, and decreased food intake, hepatic glutathione reductase (GR), glutathione peroxidase (GPX), glutathione S-transferase (GST), and superoxide dismutase (SOD) activities, hepatic phosphoenolpyruvate carboxykinase 1 (Pck1), and intestinal solute carrier family 5 member 1 (Slc5a1) mRNA levels compared with the control diet. However, the HF diet with Tucum-do-Cerrado decreased hepatic glycogen, and increased hepatic GR activity, hepatic Slc2a2 mRNA levels and serum Tnfa compared with the HF diet. Tucum-do-Cerrado decreased muscle glycogen, intestinal CAT and GPX activities, muscle PFK-1 and HK activities, and increased hepatic protein (CARB) and intestinal lipid (MDA) oxidation, hepatic GST activity, serum antioxidant potential, hepatic phosphofructokinase-1 (PFK-1) activity, intestinal solute carrier family 2 member 2 (Slc2a2), tumor necrosis factor (Tnf), interleukin-1 beta (Il1b), muscle protein kinase AMP-activated alpha 1 (Prkaa1), solute carrier family 2 member 2 (Slc2a2) mRNA levels, and serum interleukin-6 (IL-6) levels, regardless of diet type. Tucum-do-Cerrado consumption may ameliorate impaired glucose utilization in a HF diet-induced obesity model by increasing liver and muscle glucose uptake and oxidation. These data suggest that Tucum-do-Cerrado consumption improves muscle glucose oxidation in non-obese and obese rats. This response may be related to the improvement in the total antioxidant capacity of rats.

Gallic acid rescues uranyl acetate induced-hepatic dysfunction in rats by its antioxidant and cytoprotective potentials

BackgroundThe liver was identified as a primary target organ for the chemo-radiological effects of uranyl acetate (UA). Although the anti-oxidant and anti-apoptotic properties of gallic acid (GA) make it a promising phytochemical to resist its hazards, there is no available data in this area of research.MethodsTo address this issue, eighteen rats were randomly and equally divided into three groups. One group was received carboxymethyl cellulose (vehicle of GA) and kept as a control. The UA group was injected intraperitoneally with UA at a single dose of 5 mg/kg body weight. The third group (GA + UA group) was treated with GA orally at a dose of 100 mg/kg body weight for 14 days before UA exposure. UA was injected on the 15th day of the experiment in either the UA group or the GA + UA group. The biochemical, histological, and immunohistochemical findings in the GA + UA group were compared to both control and UA groups.ResultsThe results showed that UA exposure led to a range of adverse effects. These included elevated plasma levels of aspartate aminotransferase, lactate dehydrogenase, total protein, globulin, glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very-low-density lipoprotein and decreased plasma levels of high-density lipoprotein cholesterol. The exposure also disrupted the redox balance, evident through decreased plasma total antioxidant capacity and hepatic nitric oxide, superoxide dismutase, reduced glutathione, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase and increased hepatic oxidized glutathione and malondialdehyde. Plasma levels of albumin and alanine aminotransferase did not significantly change in all groups. Histopathological analysis revealed damage to liver tissue, characterized by deteriorations in tissue structure, excessive collagen accumulation, and depletion of glycogen. Furthermore, UA exposure up-regulated the immuno-expression of cleaved caspase-3 and down-regulated the immuno-expression of nuclear factor-erythroid-2-related factor 2 in hepatic tissues, indicating an induction of apoptosis and oxidative stress response. However, the pre-treatment with GA proved to be effective in mitigating these negative effects induced by UA exposure, except for the disturbances in the lipid profile.ConclusionsThe study suggests that GA has the potential to act as a protective agent against the adverse effects of UA exposure on the liver. Its ability to restore redox balance and inhibit apoptosis makes it a promising candidate for countering the harmful effects of chemo-radiological agents such as UA.

Effects of Dietary Lactic Acid Supplementation on the Activity of Digestive and Antioxidant Enzymes, Gene Expressions, and Bacterial Communities in the Intestine of Common Carp, Cyprinus carpio

The present study investigated the effects of dietary lactic acid (LA) supplementation on the growth performance, intestinal digestive/antioxidant enzymes’ activities, gene expression, and bacterial communities in common carp, Cyprinus carpio. Four diets were formulated to contain 0 g/kg LA (control), at 2.5 g/kg LA (2.5LAC), 5 g/kg LA (5LAC), and 10 g/kg LA (10LAC) and offered to the fish over a period of 56 days. The results showed that dietary 5 g/kg LA supplementation improved growth performance and feed efficiency in the fish. All LA treatments exhibited significant elevations in the intestinal trypsin and chymotrypsin activities, whereas the intestinal lipase, amylase, and alkaline phosphatase activities exhibited significant elevations in the 5LAC and 10LAC treatments. All LA treatments exhibited significant elevations in the intestinal heat shock protein 70, tumor necrosis factor-alpha, interleukin-1 beta, and defensin gene expressions, and the highest expression was observed in the 5LAC treatment. Additionally, dietary LA treatment significantly increased the lysozyme expression and Lactobacillus sp. population in the intestine of the fish, and the highest values were observed in the 5LAC and 10LAC treatments. Aeromonas sp. and Vibrio sp. populations decreased in the LA treatments, and the lowest Aeromonas sp. population was observed in the 10LAC treatment. The intestinal mucin2 and mucin5 expressions, and the hepatic reduced glutathione content, significantly increased, whereas hepatic glutathione peroxidase, glutathione reductase, and malondialdehyde significantly decreased in the 5LAC and 10LAC treatments. In conclusion, dietary 5 g/kg LA is recommended for common carp feeding to improve growth rate, antioxidant capacity, and intestinal health.

Feeding Yellow Worms to Meagre: Effects on Whole-Body Fatty Acid Profile and Hepatic and Intestine Oxidative Status.

This study aimed to determine the effects of dietary inclusion of Tenebrio molitor larvae (yellow worms) meal (TM) on meagre fish (Argyrosomus regius) whole-body fatty acids (FA) profile and hepatic and intestine oxidative status. For that purpose, fish were fed for 9 weeks a fishmeal-based diet (control) or diets including 10%, 20%, or 30% TM. With the increase in dietary TM level, whole-body oleic acid, linoleic acid, monounsaturated FA, and n-6 polyunsaturated FA (PUFA) increased while saturated FA (SFA), n-3 PUFA, n-3 long chain-PUFA, SFA:PUFA ratio, n3:n6 ratio, and FA retention decreased. Hepatic superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G6PDH), and glutathione reductase (GR) activities increased and catalase (CAT) and glutathione peroxidase (GPX) activities decreased with dietary TM inclusion. Hepatic total and reduced glutathione were lower in fish fed 20% TM. Intestinal CAT activity and oxidized glutathione increased and GPX activity decreased with dietary TM inclusion. Intestine SOD, G6PDH, and GR activities increased and malondialdehyde concentration decreased in fish fed the diets with lower TM inclusion levels. Liver and intestine oxidative stress index and liver malondialdehyde concentration were unaffected by dietary TM. In conclusion, to avoid major whole-body FA changes or antioxidant status imbalances, it is recommended to limit TM to 10% inclusion in meagre diets.

Effects of dietary β-glucan on growth rate, antioxidant status, immune response, and resistance against Aeromonas hydrophila in genetic improvement of farmed tilapia (GIFT, Oreochromis niloticus)

This study was conducted to assess the influences of dietary β-glucan on growth rate, antioxidant status, immunity response, and resistance against Aeromonas hydrophila of genetically improved farmed tilapia (GIFT, Oreochromis niloticus). Four isonitrogenous and isoenergetic diets were formulated to contain 0%, 0.2%, 0.4%, and 0.8% β-glucan, respectively. Fish with similar size (average body weight, 3.43 ± 0.02 g) were randomly distributed into 12 tanks with 40 juveniles per tank and hand-fed to apparent satiation twice daily for 10 weeks. The fish were then challenged by A. hydrophila and their cumulative survival rate was recorded for the next week. No obvious influences on growth rate and feed utilization of GIFT were induced by dietary β-glucan addition (P > 0.05). However, dietary 0.4% β-glucan inclusion increased the serum high-density lipoprotein cholesterol level but decreased the triglyceride, total cholesterol and low-density lipoprotein cholesterol levels as well as alanine aminotransferase and aspartate aminotransferase activities (P < 0.05). Similarly, the increased intestinal superoxide dismutase (SOD), peroxidase and total antioxidant capacity (TAC) activities as well as the decreased intestinal malondialdehyde (MDA) and reactive oxygen species contents were also observed in GIFT fed diet with 0.4% β-glucan (P < 0.05). Dietary addition of 0.8% β-glucan increased the plasma SOD, glutathione peroxidase (GPx), catalase, and TAC activities, but reduced the plasma MDA content (P < 0.05). Dietary β-glucan inclusion regardless of levels improved the hepatic SOD, glutathione reductase, catalase, peroxidase, TAC, and acid phosphatase activities, but depressed the hepatic nitric oxide and MDA contents (P < 0.05). Plasma lysozyme activity was improved by the inclusion of 0.4% and 0.8% β-glucan (P < 0.05); plasma immunoglobulin M, complement 3 and complement 4 contents were improved by dietary β-glucan inclusion (P < 0.05); respiratory burst activity of macrophages was improved by the addition of 0.2% β-glucan (P < 0.05). Additionally, dietary β-glucan supplementation reduced the mortality rate and increased the relative percentage survival of GIFT challenged by A. hydrophila (P < 0.05). These results indicated that suitable β-glucan inclusion (0.4–0.8%) could promote the antioxidant status, immune response and disease resistance of GIFT, and β-glucan can be used as a feed additive for GIFT.

Evaluation of Cottonseed Meal as an Alternative to Fish Meal in Diet for Juvenile Asian Red-Tailed Catfish Hemibagrus wyckioides.

A 10-week trial was performed to investigate the effects of replacing fishmeal with cottonseed meal (CSM) on the growth rate, protein metabolism, and antioxidant response of Asian red-tailed catfish Hemibagrus wyckioides. Five isonitrogenous and isocaloric diets (C0, C8.5, C17.2, C25.7, and C34.4) were prepared to contain 0%, 8.5%, 17.2%, 25.7%, and 34.4% CSM replacing fishmeal, respectively. The weight gain, daily growth coefficient, pepsin, and intestinal amylase activities initially increased and then decreased with the raising dietary CSM levels; the highest values were observed in the C17.2 group (P < 0.05). However, feed cost exhibited the opposite trend. With the increasing dietary CSM levels, the protein efficiency ratio and intestinal trypsin activity decreased but feed conversion rate increased gradually; while no differences were observed among the C0, C8.5, and C17.2 groups (P > 0.05). Dietary CSM inclusion regardless of levels increased the plasma growth hormone level as well as hepatic aspartate aminotransferase (AST) and γ-glutamyl transpeptidase activities but decreased the plasma glutamate dehydrogenase and AST activities (P < 0.05). With the increasing dietary CSM levels, the plasma alkaline phosphatase (AKP) and hepatic superoxide dismutase activities decreased but malondialdehyde content increased gradually, while no differences were observed among the C0, C8.5, and C17.2 groups (P > 0.05). The plasma immunoglobulin M content and hepatic glutathione reductase activity initially increased but then decreased with the raising dietary CSM levels; the highest values were found in the C17.2 group. These results indicated that dietary CSM inclusion level up to 17.2% improved the growth rate, feed cost, digestive enzyme activity, and protein metabolism without compromising antioxidant capacity of H. wyckioide, whereas these parameters were depressed by further inclusion of CSM. CSM is a potentially cost-effective alternative plant protein source in diet of H. wyckioide.

Alleviation of transportation-induced stress in Nile tilapia, Oreochromis niloticus, using brackish water

Fish transportation is associated with drawbacks such as stress, hydromineral imbalance, and oxidative stress. Thus, it worth finding methods to improve fish health and welfare during transportation. Adding salt to transportation water decreases osmotic stress and energy expenditure; thus, the objective of this work was to evaluate the effects of different concentrations of salt (0, 2, and 4 g/L) added in the transportation water on the stress and antioxidant parameters of Nile tilapia, Oreochromis niloticus, after 3 h transportation. The fish (38.2 ± 2.69 g) were sampled before (control), immediately and 24 h after transportation. After transportation, there were elevations in the plasma cortisol and glucose levels in all treatments; however, the salt-treated fish exhibited lower elevations in these parameters. The plasma sodium, chloride, and the hepatic alanine aminotransferase activity decreased; whereas the plasma total protein, albumin, and the hepatic malondialdehyde and lactate dehydrogenase significantly increased after transportation in 0 g/L salt treatment. The plasma sodium level stayed decreased after 24 h recovery in 0 g/L salt treatment; whereas, the hepatic alanine aminotransferase decreased in 4 g/L salt treatment, at this time. After transportation, there were significant elevations in the hepatic superoxide dismutase and glutathione peroxidase, as well as significant decreases in the hepatic glutathione reductase, aspartate aminotransferase, and reduced glutathione in 0 and 2 g/L salt treatments. The hepatic superoxide dismutase and glutathione peroxidase remained elevated, after 24 h recovery in 0 g/L salt treatment. There were significant decreases in the hepatic CAT activity after transportation in the salt-treated fish, and after recovery in all treatments. In conclusion, addition of 4 g/L salt to transportation water reduces stress, hepatic damage and oxidative stress, and hydromineral imbalance in Nile tilapia.

Dietary magnolol inclusion improves the antioxidant and immune responses, and resistance to Aeromonas hydrophila in genetically improved farmed tilapia (Oreochromis niloticus)

A 10-week feeding trial was conducted to evaluate the effects of dietary magnolol inclusion on the growth rate, antioxidant and immune responses of genetically improved farmed tilapia Oreochromis niloticus. Four experimental diets were formulated with 0%, 0.02%, 0.04% and 0.08% magnolol, respectively. Dietary 0.02–0.08% magnolol inclusion did not affect the growth rate and feed utilization of tilapia. However, dietary 0.02–0.08% magnolol inclusion increased the plasma catalase, the intestinal alkaline phosphatase (ALP), and the hepatic glutathione reductase (GR) and catalase activities; but reduced the hepatic malondialdehyde (MDA) content. Further, supplementation with 0.04–0.08% magnolol increased the plasma superoxide dismutase (SOD), peroxidase, ALP and total antioxidant capacity (TAC), the intestinal GR, catalase, peroxidase and TAC, and the hepatic SOD and TAC activities; but decreased the plasma MDA, the intestinal MDA and reactive oxygen species contents. Dietary 0.02–0.04% magnolol inclusion increased the plasma complement 3 content, whereas the plasma immunoglobulin M, complement 4 contents and lysozyme activity were increased by dietary 0.04–0.08% magnolol inclusion. The phagocytic activity of head kidney macrophages was increased by the inclusion of 0.04% magnolol. Additionally, supplementation with 0.02–0.08% magnolol increased the relative percentage survival of tilapia after infection with Aeromonas hydrophila. These results indicated that 0.04% magnolol inclusion improved the antioxidant and immune responses without compromising growth performance of tilapia, suggesting that magnolol could be used as an antioxidant and immunostimulant in aquafeed.

Dietary supplementation with Gracilaria sp. by-products modulates stress response, antioxidant and immune systems of gilthead seabream (Sparus aurata) exposed to crowding

By-products obtained from seaweed processing appear as a promissory source of bioactive compounds that could be included in aquafeed to improve the sustainability of aquaculture. Therefore, the present study aimed to evaluate the effects of dietary supplementation with by-products obtained from the seaweed Gracilaria sp. on the stress response, antioxidant, and immune systems of gilthead seabream (Sparus aurata) exposed to an acute crowding event. For this, fish were fed six experimental diets: (i) a diet containing a commercial antioxidant (CTR), (ii) a diet without antioxidant addition (NO-AOX), (iii) a NO-AOX diet with 0.5% ethanolic extract (0.5% EE), (iv) a NO-AOX diet with 5% ethanolic waste (5% EEW), (v) a NO-AOX diet with 5% agar waste (5% AW), and (vi) a NO-AOX diet with 2.5% agar waste (2.5% AW) for 59 days. After this period, fish were exposed to 1 h of crowding (100 kg m−3) and sampled immediately after 0 and at 24 h post-crowding. Our results showed that the fish-fed AW and EEW diets showed lower plasma cortisol levels than those fed the CTR diet, suggesting an improved stress response to crowding on these groups. No differences were detected on hepatic lipid peroxidation levels between dietary groups after crowding. However, the fish fed 0.5% EE diet showed lower hepatic glutathione reductase (GR) activity than fish fed the NO-AOX diet. Additionally, glutathione peroxidase (GPx) activity was decreased in the liver of fish fed 2.5% and 5% AW diets compared with the other dietary groups. Concerning immune parameters, the plasma peroxidase activity was higher in fish fed the 2.5% AW diet than fish fed NO-AOX or 5% EEW diets, suggesting a modulatory effect of dietary AW at 2.5% in the humoral immune response in crowded fish. Results suggest that dietary supplementation with AW, particularly when supplemented at 2.5%, could be used as a dietary tool to mitigate oxidative stress when improving immune response in gilthead seabream exposed to a stressor as crowding.

Protective mechanisms of piperine against acetaminophen-induced hepatotoxicity may be mediated through TGFBRAP1.

To investigate the possible protective mechanisms of piperine against acetaminophen (APAP)-induced hepatotoxicity in mice. Mice were given APAP (650 mg/kg i.p. once) with or without pretreatment with piperine (50 mg/kg/day orally for 3 days). APAP caused liver toxicity as indicated by increased serum alanine aminotransferase and liver microscopic pathology, decreased hepatic superoxide dismutase and glutathione reductase activities, without affecting nuclear factor erythroid 2-related factor 2 (Nrf2) expression. APAP administration induced inflammation and apoptosis manifested as increased NF-κB p65 and dysregulation of caspase 3/Bcl2 expression, respectively. In addition, APAP increased the expression of transforming growth factor-β receptor-associated binding protein 1 (TGFBRAP1). On the other hand, pretreatment with piperine improved liver function and structure, reserved hepatic antioxidative defense, and attenuated inflammatory and apoptotic markers. Interestingly, piperine administration enhanced hepatic TGFBRAP1 expression compared to APAP alone. The hepatoprotective effects of piperine against APAP are mediated via its antioxidant, anti-inflammatory, and anti-apoptotic effects, in addition to regulation of TGFBRAP1.

Dietary taurine supplementation affects lipid metabolism and improves the oxidative status of European seabass (Dicentrarchus labrax) juveniles

The aim of this study was to assess the effect of dietary taurine (Tau) in intermediary metabolism, oxidative status, and Tau biosynthesis capacity in European seabass juveniles. For that purpose, four diets (45% protein and 18% lipid) were formulated with increasing levels of Tau (0.2, 0.5, 0.7, and 1.2% of DM) and fed to triplicate groups of fish (IBW 55g) until apparent visual satiety for 10 weeks.Total bile acid content in the liver increased as dietary Tau supplementation increase, while the opposite occurred in the plasma. Plasma glucose, total cholesterol, HDL, and LDL cholesterol decreased, while total and indirect bilirubin increased with the increase of dietary Tau level.The activity of the key intermediary enzymes measured decreased with the increase of dietary Tau up to 0.7%. Regarding the antioxidant-related enzymes, dietary Tau supplementation decreased hepatic catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase activities with the maximum effects being observed as dietary Tau increased from 0.2 to 0.5%. Overall, there was a decreasing trend of hepatic lipid peroxidation with the increase of dietary Tau.This study is the first to demonstrate that in European seabass juveniles the capacity of expressing cysteine dioxygenase, an enzyme involved in the cysteine sulfinate pathway for Tau synthesis, although its expression was not affected by Tau levels in the diet.This study indicates that dietary Tau levels affect intermediary metabolism, namely carbohydrates and lipidic metabolism, and improve the antioxidant status of European seabass juveniles. Furthermore, although CDO expression was detected, European seabass seems unable to regulate its activity, these results supporting the essentiality of Tau for this species.

Paracetamol-induced metabolic and cardiovascular changes are prevented by exercise training.

Paracetamol (PAR) is the most frequently consumed non-prescription drug, yet it is well known to induce toxicity. Here, we have evaluated the effects of exercise training on vascular dysfunction induced by PAR. Rats were distributed among four groups: (a) Sedentary; (b) Exercise; (c) Sedentary+PAR; and (d) Exercise+PAR. The exercise comprised swimming 50min/d, 5d/wk for 6weeks (+PAR in the last 2weeks, at 400mg/kg/d/p.o.). After killing, the rats' blood and aortas were collected for biochemical analysis of hepatic transaminases, TBARs reaction, glutathione, glutathione reductase, SOD, and catalase. In vitro vascular relaxation was measured using acetylcholine and sodium nitroprusside in the presence or absence of tiron (an antioxidant). Vascular protein expression (eNOS and sGC) also were analysed. Increased transaminases after PAR treatment were found to be reduced by exercise. Vasodilation was impaired by PAR only in the sedentary group. Exercise prevented alterations in lipoperoxidation and glutathione levels after PAR exposure. Glutaathione reductase and SOD also were increased by PAR but were normalized in the exercised group. Catalase activity and protein expressions did not change in any group. PAR treatment caused impairment in both vasodilation and redox balance; however, exercise training prevented the vascular and redox system dysfunction induced by PAR treatment.

How Does Ginsenoside Rh2 Mitigate Adipogenesis in Cultured Cells and Obese Mice?

Ginsenoside Rh2, an intermediate metabolite of ginseng, but not naturally occurring, has recently drawn attention because of its anticancer effect. However, it is not clear if and how Rh2 inhibits preadipocytes differentiation. In the present study, we hypothesized that ginsenoside Rh2 attenuates adipogenesis through regulating the peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway both in cells and obese mice. Different concentrations of Rh2 were applied both in 3T3-L1 cells and human primary preadipocytes to determine if Rh2 inhibits cell differentiation. Dietary Rh2 was administered to obese mice to determine if Rh2 prevents obesity in vivo. The mRNA and protein expression of PPAR-γ pathway molecules in cells and tissues were measured by real-time polymerase chain reaction (RT-PCR) and Western blot, respectively. Our results show that Rh2 dose-dependently (30–60 μM) inhibited cell differentiation in 3T3-L1 cells (44.5% ± 7.8% of control at 60 μM). This inhibitory effect is accompanied by the attenuation of the protein and/or mRNA expression of adipogenic markers including PPAR-γ and CCAAT/enhancer binding protein alpha, fatty acid synthase, fatty acid binding protein 4, and perilipin significantly (p < 0.05). Moreover, Rh2 significantly (p < 0.05) inhibited differentiation in human primary preadipocytes at much lower concentrations (5–15 μM). Furthermore, dietary intake of Rh2 (0.1 g Rh2/kg diet, w/w for eight weeks) significantly (p < 0.05) reduced protein PPAR-γ expression in liver and hepatic glutathione reductase and lowered fasting blood glucose. These results suggest that ginsenoside Rh2 dose-dependently inhibits adipogenesis through down-regulating the PPAR-γ pathway, and Rh2 may be a potential agent in preventing obesity in vivo.

An in vivo and in vitro comparison of the effects of amoxicillin, gentamicin, and cefazolin sodium antibiotics on the mouse hepatic and renal glutathione reductase enzyme.

Despite the fact that the use of antibiotics is increasing worldwide, it is clear that antibiotics can lead to oxidative stress. This is the first study to make a comparison of the impact of frequently prescribed antibiotics, including amoxicillin, gentamicin, and cefazolin sodium, on the gene, protein, and activity of glutathione reductase (GR), which is one of the primary antioxidant enzymes, in mouse liver and kidney tissues. First, the GR enzyme was purified by the 2',5'-ADP Sepharose 4B affinity chromatography with a specific activity of 84.615 EU/mg protein and 9.63 EU/mg protein from the mouse liver and kidney, respectively. The in vitro inhibitory effects of the antibiotics in question was determined. While cefazolin sodium did not exhibit any inhibitory effect, gentamicin and amoxicillin inhibited GR activity in both tissues. Furthermore, the in vivo effects of these drugs were investigated, and amoxicillin and cefazolin sodium-inhibited GR activity in both liver and kidney tissues, while gentamicin did not have any effect on the kidney. Besides, while gentamicin downregulated and cefazolin sodium upregulated Gr gene expression, amoxicillin did not alter it. Protein expression was only affected by the administration of cefazolin sodium in the kidney. This study is important as it demonstrates that while amoxicillin and gentamicin showed parallel effects on the GR activity in liver and kidney tissues both in vitro and in vivo, cefazolin sodium had a very strong effect on hepatic and renal GR in vivo. Furthermore, the antibiotics used in this study induced oxidative stress in both tissues.

Commiphora myrrha Resin Alcoholic Extract Ameliorates High Fat Diet Induced Obesity via Regulation of UCP1 and Adiponectin Proteins Expression in Rats.

This study was performed to evaluate anti-obesity potential of Commiphora myrrha resin ethanolic extract (CME) with the respect to expression of leptin, adiponectin and uncoupling protein 1 (UCP1) in rats. Control rats fed basal diet. Second group fed basal diet and administered CME (500 mg/kg bw) orally for 14 weeks. Third group fed high fat diet (HFD) for 14 weeks. Fourth group fed HFD and administered CME as second group. Fifth group fed HFD for 8 weeks then fed basal diet and administered CME as third group for another 6 weeks. Phytochemical analysis of CME identified the presence of germacrene B, 1,4-benzoquinone, benzofuran, hexadecanoic acid, 9,12-octadecnoic acid methyl ester, reynosin, 11, 14-eicosadienoic acid, isochiapin B, bisabolene epixod, elemene and 1-heptatriacotanol. High fat diet significantly increased food intake, body weight, hyperglycemia, serum levels of total cholesterol, triacylglycerol, low density lipoprotein and ketone bodies, AST and AST activities, concentration of malondialdehyde and histopathological changes in hepatic tissues. However, it significantly reduced serum levels of high density lipoprotein, leptin and adiponectin, activity of hepatic glutathione reductase (GR) and brown adipose tissue UCP1 protein expression. In contrast, CME ameliorated HFD increased body weight, hyperglycemia, dyslipidemia, ketonemia, hepatic tissues lipid peroxidation, restored hepatic tissue architecture and enhanced protein expression of leptin, adiponectin and UCP1 and activity of hepatic GR. This study indicated that CME ameliorated HFD induced hyperglycemia and dyslipidemia through normalization of HFD reduced leptin, adiponectin and UCP1 proteins production and antioxidant activity.

Survival strategies of Wuchang bream (Megalobrama amblycephala) juveniles for chronic ammonia exposure: Antioxidant defense and the synthesis of urea and glutamine

This study aimed to explore how Wuchang bream (Megalobrama amblycephala) survive and defend against the toxicity of ambient total ammonia nitrogen (0, 5, 10, 20 and 30 mg/L TA-N) during 30-day exposure. As a result, hepatic malondialdehyde and protein carbonylation as well as histopathological alterations increased with increasing TA-N level, which suggested that chronic ammonia exposure caused oxidative stress and damage in the liver of fish. Meanwhile, the activities of hepatic total superoxide dismutase (T-SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glucose 6-phosphate dehydrogenase (G6PD) as well as the mRNA expression of Cu/Zn sod, cat, gpx and g6pd were elevated significantly along with significant reduction of glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) (P < 0.05). These results indicated that hepatic antioxidant responses were activated to alleviate oxidative damages induced by ammonia, in which lower-concentration ammonia only initiate SOD-CAT-GR-G6PDH defense and higher ammonia activated the SOD-CAT-GPx-GSH-GR-G6PDH antioxidant response. In addition, significant increases of serum urea and hepatic ammonia, urea, glutamine, arginase as well as glutamine synthetase were detected with the increase of TA-N (P < 0.05), while serum ammonia levels kept stable (P > 0.05). The present findings further revealed that ammonia could be detoxified directly into glutamine and urea in Wuchang bream to cope with ammonia exposure. In conclusion, under chronic ammonia exposure, enhanced hepatic antioxidant responses as well as increased urea and glutamine synthesis worked in combination to allow Megalobrama amblycephala to defend against environmental ammonia toxicity.

Comparative Analysis of Luteolin and Luteolin-7-O-Glucoside on anti-Atherogenesis in ApoE Knockout Mice with Hyperhomocysteinemia

AbstractLuteolin is a naturally occurring flavone that reportedly has anti-inflammatory effect. Flavones in plants are usually present in the form of glucosides, although occasionally they are found as aglycones. The bioavailability of flavones may differ when consumed as either aglycones or glucosides. Nonetheless, numerous studies focused on the biological activity of flavonoid aglycones or that in vitro. These findings are supporting reason to compare the anti-atherogenic effect of aglycone and glucoside forms of flavones in vivo. Male ApoE knockout mice (n = 28, 6-week-old) were divided randomly into 4 groups of 7 mice: negative control group, homocysteine control group, luteolin and luteolin7-O-glucoside groups with homocysteine. All animals were fed by a high-fat diet, modified by AIN-93, containing 0.5% of cholesterol and 45% of fat. Luteolin and luteolin-7-O-glycoside were given daily by gavage for 5 weeks (50 mg/kg BW, respectively). To induce hyperhomocysteinemia, homocysteine was provided as a drinking water (0.9g/L). Administration of homocysteine did not affect body weight gain, feed intake and feed efficiency ratio among groups. Homocysteine feeding sharply increased serum concentrations of homocysteine and triglyceride as well as adhesion molecules including monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1, which were attenuated by the administration of luteolin and luteolin-7-O-glucoside (p &lt; 0.05). Homocysteine administration produced development of atherosclerotic process by the induction of hepatic inducible nitric oxide synthase and cyclooxygenase-2 as well as aortic intercellular adhesion molecule expressions along with diminished expressions of antioxidative enzymes, such as hepatic glutathione reductase (GR), aortic GR and glutathione peroxidase (p &lt; 0.05). Administration of both flavones down-regulated expressions of inflammatory mediators and adhesion molecules as well as up-regulated expressions of antioxidative enzymes (p &lt; 0.05). These data were in accordance with the histopathological observations which were analyzed by hematoxylin and eosin (H&amp;E) stain and immunohistochemistry. In a comparison of both agents, luteolin more potently attenuated inflammation and oxidative stress than luteolin-7-O-glucoside. These results exhibit that luteolin and luteolin-7-O-glycoside ameliorated atherogenic processes through the regulation of inflammation and oxidative stress in ApoE knockout mice with hyperhomocysteinemia. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government of MOE (No 201704340001).

Influence of Dietary Astaxanthin on the Hepatic Oxidative Stress Response Caused by Episodic Hyperoxia in Rainbow Trout.

A 13-week feeding trial was carried out with juvenile rainbow trout to test two diets: a control diet without astaxanthin (AX) supplementation (CTRL diet), and a diet supplemented with 100 mg/kg of synthetic AX (ASTA diet). During the last week of the feeding trial, fish were exposed to episodic hyperoxia challenge for 8 consecutive hours per day. Episodic hyperoxia induced physiological stress responses characterized by a significant increase in plasma cortisol and hepatic glycogen and a decrease in plasma glucose levels. The decrease of plasma glucose and the increase of hepatic glycogen content due to episodic hyperoxia were emphasized with the ASTA diet. Hyperoxia led to an increase in thiobarbituric acid-reactive substances in the muscle, diminished by dietary AX supplementation in both liver and muscle. Muscle and liver AX were increased and decreased respectively after 7-day episodic hyperoxia, leading to an increase in flesh redness. This augment of muscle AX could not be attributed to AX mobilization, since plasma AX was not affected by hyperoxia. Moreover, hyperoxia decreased most of antioxidant enzyme activities in liver, whereas dietary AX supplementation specifically increased glutathione reductase activity. A higher mRNA level of hepatic glutathione reductase, thioredoxin reductase, and glutamate-cysteine ligase in trout fed the ASTA diet suggests the role of AX in glutathione and thioredoxin recycling and in de novo glutathione synthesis. Indeed, dietary AX supplementation improved the ratio between reduced and oxidized glutathione (GSH/GSSG) in liver. In addition, the ASTA diet up-regulated glucokinase and glucose-6-phosphate dehydrogenase mRNA level in the liver, signaling that dietary AX supplementation may also stimulate the oxidative phase of the pentose phosphate pathway that produces NADPH, which provides reducing power that counteracts oxidative stress. The present results provide a broader understanding of the mechanisms by which dietary AX is involved in the reduction of oxidative status.

Bisphenol A-induced oxidative damage in the hepatic and cardiac tissues of rats: The modulatory role of sesame lignans.

Bisphenol A (BPA) is an environmental pollutant that is widely produced throughout the world. It is primarily used in the manufacture of polycarbonate plastics, epoxy resins, paints and dental materials. BPA has been reported to promote hepatotoxicity and cardiotoxicity. The antioxidant activity of sesame lignans is well established. The current study assessed the protective efficiency of sesame lignans against BPA-induced hepatotoxicity and cardiotoxicity. Rats were divided into 4 groups: A control group, a BPA-treated group, a sesame lignans-treated group and a sesame lignans and BPA-treated group. Rats were orally administered their respective doses daily [30 mg/kg body weight (BW) BPA and/or 20 mg/kg BW sesame lignans] for 6 weeks. Liver function tests were performed using serum of all groups. Lipid profile and antioxidant status were also measured in liver tissue of the studied groups. The results were confirmed by histopathological examination of liver and heart tissues. The oral administration of BPA was revealed to elicit significant decreases in the activities of hepatic glutathione peroxidase, glutathione reductase, superoxide dismutase and glutathione. It also significantly increased levels of malondialdehyde. Furthermore, BPA-treatment resulted in lipid accumulation, elevated activities of alanine aminotransferase, creatine kinase MB and lactate dehydrogenase, and histological changes of liver and heart tissues. However, the co-administration of sesame lignans and BPA attenuated hepatotoxicity, cardiotoxicity and BPA-induced histological changes. The results of the current study indicated that sesame lignans may be helpful in the development of novel natural drugs to treat hepatic and cardiovascular disorders.