Hepatic Glutathione S-transferase Activity Research Articles

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.

Comparisons between human and rodent hepatic glutathione S-Transferase activities reveal sex and species differences

Glutathione S-transferases (GSTs) are conjugating enzymes involved in drug metabolism, antioxidant defence, and cell signalling. Herein, we investigated hepatic GST conjugation in several mouse and rat strains, including both sexes, with a direct comparison to humans. Using general and isoform-selective substrates, all mouse strains had significantly greater activities than humans for total cytosolic GST, GST-M, GST-T, and microsomal GST activities. Some strains had significantly greater GST-P activities compared to humans. Sex differences between males and females were evident in all strains for total cytosolic GST, GST-M, and GST-P, and sex differences in GST-T and microsomal GST activities within strains were noted. All rats had significantly greater activities than humans for GST-M and GST-T; only some strains were significantly greater than humans for GST-P, total cytosolic GST, and microsomal GST. Sex differences within strains showed significantly greater GST-M and GST-T activities in males compared to females. Select strains showed sex differences for total cytosolic and microsomal GST activities; there were no sex differences in GST-P activities. Significant differences in glutathione conjugation between humans and rodents exist, including sex differences. This highlights the need for careful animal selection in pre-clinical studies where GSTs are the primary metabolic pathway.

Effects of Chinese gallnut tannic acid on growth performance, blood parameters, antioxidative status, intestinal histomorphology, and cecal microbial shedding in broilers challenged with aflatoxin B1.

The objective of the present study was to investigate the effects of tannic acid (TA) on growth performance, blood parameters, antioxidant capacity, and intestinal health in broilers challenged with aflatoxin B1 (AFB1). A total of 480 broilers aged 1 d were randomly allotted into four treatments: 1) CON, control diet; 2) AF, CON + 60 μg/kg AFB1 of feed during days 1 to 21, CON + 120 μg/kg AFB1 of feed during days 22 to 42; 3) TA1, AF + 250 mg/kg TA; and 4) TA2, AF + 500 mg/kg TA. Average daily gain (ADG) and average daily feed intake (ADFI) were increased in the TA1 during days 1 to 21, days 22 to 42, and days 1 to 42 compared with CON and AF treatments (P < 0.05). Broilers fed the TA2 diet had greater ADG and ADFI than those fed the CON and AF diets during the finisher and the whole period (P < 0.05). Administration of TA decreased the relative weight of liver and kidney compared with broilers fed the AF diet on day 42 (P < 0.05). The blood activity of alanine transferase (ALT) and gamma-glutamyl transferase (GGT) was increased in the AF treatment compared with the CON (P < 0.05). Broilers fed the TA1 decreased the ALT content on day 21, and the level of ALT and GGT was decreased in the TA2 compared with the AF group on day 42 (P < 0.05). The activity of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) in plasma, and the hepatic glutathione S-transferase (GST) was decreased in the AF group compared with the CON group (P < 0.05). The TA decreased plasma malondialdehyde concentration, and increased plasma T-SOD, GSH-Px, total antioxidant capacity, and hepatic GST activity compared with the AF (P < 0.05). The crypt depth of the jejunum was decreased in the TA1 treatment on day 21, and the villus height of the ileum was increased in the TA2 group on day 42 compared with the AF treatment (P < 0.05). The cecal Lactobacillus counts on day 21 were tended to increase in the TA treatments compared with the AF (P = 0.061). In conclusion, dietary inclusion of 250 and 500 mg/kg TA could improve the growth, antioxidant capacity, and partially protected the intestinal health of broilers challenged with AFB1.

Characterization of Cytosolic Glutathione S-Transferases Involved in the Metabolism of the Aromatase Inhibitor, Exemestane.

Exemestane (EXE) is a hormonal therapy used to treat estrogen receptor-positive breast cancer by inhibiting the final step of estrogen biosynthesis catalyzed by the enzyme aromatase. Cysteine conjugates of EXE and its active metabolite 17β-dihydro-EXE (DHE) are the major metabolites found in both the urine and plasma of patients taking EXE. The initial step in cysteine conjugate formation is glutathione conjugation catalyzed by the glutathione S-transferase (GST) family of enzymes. The goal of the present study was to identify cytosolic hepatic GSTs active in the GST-mediated metabolism of EXE and 17β-DHE. Twelve recombinant cytosolic hepatic GSTs were screened for their activity against EXE and 17β-DHE, and glutathionylated EXE and 17β-DHE conjugates were detected by ultra-performance liquid chromatography tandem mass spectrometry. GST α (GSTA) isoform 1, GST μ (GSTM) isoform 3 and isoform 1 were active against EXE, whereas only GSTA1 exhibited activity against 17β-DHE. GSTM1 exhibited the highest affinity against EXE with a Michaelis-Menten constant (KM) value that was 3.8- and 7.1-fold lower than that observed for GSTA1 and GSTM3, respectively. Of the three GSTs, GSTM3 exhibited the highest intrinsic clearance against EXE (intrinsic clearance = 0.14 nl·min-1·mg-1). The KM values observed for human liver cytosol against EXE (46 μM) and 17β-DHE (77 μM) were similar to those observed for recombinant GSTA1 (53 and 30 μM, respectively). Western blot analysis revealed that GSTA1 and GSTM1 composed 4.3% and 0.57%, respectively, of total protein in human liver cytosol; GSTM3 was not detected. These data suggest that GSTA1 is the major hepatic cytosolic enzyme involved in the clearance of EXE and its major active metabolite, 17β-DHE. SIGNIFICANCE STATEMENT: Most previous studies related to the metabolism of the aromatase inhibitor exemestane (EXE) have focused mainly on phase I metabolic pathways and the glucuronidation phase II metabolic pathway. However, recent studies have indicated that glutathionylation is the major metabolic pathway for EXE. The present study is the first to characterize hepatic glutathione S-transferase (GST) activity against EXE and 17β-dihydro-EXE and to identify GST α 1 and GST μ 1 as the major cytosolic GSTs involved in the hepatic metabolism of EXE.

Telomerase activator-65 and pomegranate peel improved the health status of the liver in aged rats; multi-targets involved.

Objective(s):This study was undertaken to investigate the efficacy of telomerase activator-65 (Ta-65) and pomegranate peel against aging-induced deteriorations in the liver. Materials and Methods: The rats were divided into four groups: control, aged, aged rats treated with Ta-65, and pomegranate orally for two months.Results:Aging significantly increased the serum levels of total protein, globulins, and protein carbonyl and reduced the insulin-like growth factor 1 (IGF-1). It also elevated the hepatic malondialdehyde and decreased the hepatic glutathione S-transferase (GST) activity. Aging elevated the expression of thioredoxin reductase1, telomerase reverse transcriptase, and cytochrome 3a1 in the liver; it increased the p53 protein level and elevated the activity of caspase-3 in the liver indicating the occurrence of apoptosis. The architecture of the liver deteriorated in the aged rats, as shown by both light and electron microscopy examinations. The liver of the aged rats had many apoptotic hepatocytes with shrunken nuclei. Many hepatocytes had dilated rough endoplasmic reticulum, many lysosomes, and many fat droplets. Administration of Ta-65 and pomegranate to the aged rats normalized most of the previous biochemical parameters and improved the liver architecture. Conclusion:Ta-65 and pomegranate have anti-aging activity through targeting multiple cellular pathways. It is also noteworthy that Ta-65 was superior to pomegranate in its alleviative effects.

Antioxidant effects of gum arabic on gentamycin-induced hepatotoxicity in rats

Background Gum arabic (GA) is an exudate obtained from Acacia senegal and A. seyal, and it contains a large amount of nonviscous soluble fiber. Experimental studies revealed its strong antioxidant properties. Gentamycin-induced hepatotoxicity has been reported in experimental animals. Gentamycin induces hepatoxicity mainly by generating free radicals and enhancing oxidative stress. Aim This study aimed to investigate the involvement of oxidative stress and the alteration of the oxidant–antioxidant balance in gentamycin-induced hepatotoxicity. In addition, this study explored the possible protection that can be afforded by GA, given its antioxidant potential. Materials and methods Forty adult male Albino rats’ weighing was used in this study. The animals were randomly divided into four groups. Group I served as control, which received normal mouse diet. Group II orally received GA through a gastric feeding tube for 8 days. Group III received a daily intraperitoneal injection of gentamycin. Group IV received gentamycin intraperitoneally plus orally for 8 days. Results The results of this study revealed significant elevation of serum alanine transaminase, hepatic malondialdehyde level, glutathione peroxidase, and glutathione S-transferase activities and reduction of hepatic Reduced Glutathione (GSH) and glutathione reductase activities in gentamycin-treated animals. Administration of GA with gentamycin intake restored the altered parameters to their normal values, whereas hepatic glutathione peroxidase and glutathione S-transferase activities were enhanced further. Conclusion This study demonstrated the antioxidant effect of GA and its protective role against gentamycin-induced hepatocyte injury. More studies are warranted to further reveal the underlying mechanisms of the antioxidant properties of GA, especially at the structural and molecular levels.

Diazinon exposure produces histological damage, oxidative stress, immune disorders and gut microbiota dysbiosis in crucian carp (Carassius auratus gibelio).

Diazinon is a common organophosphate pesticide widely used to control parasitic infections in agriculture. Excessive use of diazinon can have adverse effects on the environment and aquatic animal health. In the present study, the toxic effects of diazinon on the histology, antioxidant, innate immune and intestinal microbiota community composition of crucian carp (Carassius auratus gibelio) were investigated. The results showed that diazinon at the tested concentration (300μg/L) induced gill and liver histopathological damages. Hepatic total superoxide dismutase (T-SOD), catalase (CAT), and glutathione S-transferase (GST) activities significantly decreased (P<0.05) by 32.47%, 65.33% and 37.34%, respectively. However, the liver tissue malondialdehyde (MDA) content significantly (P<0.05) increased by 138.83%. The 300μg/L diazinon significantly (P<0.05) downregulated the gene expression of TLR4, MyD88, NF-kB p100 and IL-8 but had no significant effect TNF-α (P=0.8239). In addition, the results demonstrated that diazinon exposure could affect the intestinal microbiota composition and diversity. Taken together, the results of this study indicated that diazinon exposure can cause damage to crucian carp, induce histopathological damage in gill and liver tissues, oxidative stress in the liver, and innate immune disorders and alter intestinal microbiota composition and diversity.

Organophosphorus flame retardant induced hepatotoxicity and brain AChE inhibition on zebrafish (Danio rerio)

Organophosphorus flame retardants (OPFRs) are high production volume (HPV) chemicals. Recent reports reveal that OPFRs are ubiquitous in the environment. Unfortunately, the toxicity profiles for OPFRs on organisms remain limited. Hence, to illustrate the potential toxic effects of OPFRs at environmental relevant concentrations on aquatic biota, in the present study, we investigated biochemical, enzymological, antioxidants, and histological (at long-term study) changes of zebrafish tissues under short- (96 h) and long- (21 days) -term triphenyl phosphate (TPhP) exposure. The hepatic glucose production (except short-term TPhP treatment up to 48 h), aspartate transaminase, alanine transaminase, lactate dehydrogenase, reactive oxygen species generation, lipid peroxide, and catalase activities were found to be increased in TPhP exposed groups when compared to control groups (normal and solvent control groups). The hepatic protein content and sodium dismutase activity were declined in TPhP exposed groups. Likewise, brain tissue acetylcholinesterase activity was declined in TPhP exposed groups. The hepatic glutathione S-transferase activity increased after 24 h under short-term TPhP exposure (96 h), while under long-term exposure period (21 days) the enzyme activity was accelerated when compared to control groups. Long-term TPhP exposure resulted in a series of morphological anomalies in the hepatic tissues of zebrafish. Our study reveals that TPhP can potentially cause antioxidants imbalance, alterations in enzymological and biochemical profiles, and morphological anomalies in hepatic tissues of zebrafish. Moreover, TPhP could cause neurotoxic effects on zebrafish at studied concentrations. Our findings expand the available toxicity profiles for TPhP on aquatic biota and propose that zebrafish are a good indicator, and studied parameters are valid biomarkers in assessing the eco-toxicological effects of OPFRs.

Effects of glycerol monolaurate on growth and physiology of chicks consuming diet containing fumonisin

Glycerol monolaurate (GML) is composed of lauric acid and glycerol. Research has shown that such organic acids can minimize negative effects caused by mycotoxins. Therefore, the objective of this study was to determine whether adding GML (free or encapsulated) to chick feed minimizes the effects of natural contamination by fumonisin (Fusarium verticillioides), evaluating parameters such as biochemistry, antioxidant properties, histological analysis and chick growth. Were weighed 84 chicks of the Cobb 500 strain and randomly distributed them into six groups of two replicates each (n = 14). The F group consumed feed containing fumonisin (levels 400 ppb), with no performance enhancer; F + ZB- feed with fumonisin (levels 400 ppb) + zinc bacitracin; F + GLM100 - feed with fumonisin (levels 400 ppb) + 100 mg of GML/kg of feed; F + NGLM4 - feed with fumonisin (levels 400 ppb) + 4 mg GML/kg in nanocapsules added to the feed; F + NGLM8 - fumonisin feed (levels 400 ppb) + 8 mg GML/kg in nanocapsules in the feed; and F0 - fumonisin-free feed (negative control) + zinc bacitracin. The body weights of birds fed with feed fumonisin-contaminated feed (F, F + ZB, F + GLM100, F + NGLM4 and F + NGLM8) were significantly lower (P < 0.05) than those of the negative control (F0), despite the use of GML (free and nanoencapsulated). Serum levels of triglycerides, globulins and cholesterol were significantly lower in the F0 group than in the other groups (P < 0.05), except for the F + NGLM8 group. Significantly greater levels of lipid peroxidation were observed in livers in the groups that consumed fumonisin than in the control group (F0) (P < 0.05). Serum levels of reactive oxygen species were significantly lower in groups F + NGLM8 and F0 than in the other treatments (P < 0.05). Superoxide dismutase activity was significantly greater in groups F + NGLM8 and F0 than in groups F, F + ZB and F + NGLM4. Hepatic catalase activity was significantly lower in birds that consumed contaminated feed (F, F + ZB, F + GLM100, F + NGLM4 and F + NGLM8) than in the control group (F0). Greater hepatic glutathione S-transferase activity was observed in the F + NGLM8 group than in the F0 group. Despite changes in cellular lesions in the liver, no histological changes were observed in the liver or intestines, even though visually there was yellowing of the liver. Taken together, the data suggest that free or nano-encapsulated GML did not minimize oxidative stress caused by fumonisin, and consequently, these birds had less weight gain.

Dietary supplementation with caffeine increases survival rate, reduces microbial load and protects the liver against Aeromonas hydrophila-induced hepatic damage in the grass carp Ctenopharyngodon idella

The indiscriminate use of antibiotics is a major concern for the aquaculture industry because of the increasing prevalence of bacterial resistance, including the emergence of multi-resistant strains of Aeromonas hydrophila. Therefore, alternative ecofriendly therapeutic or prophylactic approaches such as natural products have been suggested, including caffeine, a methylxanthine with potent bactericidal and antioxidant properties. The aims of this study were to evaluate whether dietary supplementation with caffeine exerted bactericidal effects against A. hydrophila, and to determine whether caffeine protected the liver of grass carp (Ctenopharyngodon idella) against A. hydrophila-induced oxidative damage. Experiment I evaluated the antimicrobial properties of caffeine dietary supplementation linked to longevity and mortality rates during aeromonosis. Fish infected with A. hydrophila that were fed diets containing 5% and 8% caffeine lived significantly longer than those fed with control diets. Experiment II evaluated hepatic oxidative stress-related parameters and microbial loads on day 7 post-infection. Levels of hepatic reactive oxygen species (ROS), lipid peroxidation (LOOH) and protein carbonylation (PC) levels were significantly higher in infected fish fed with control diet than in uninfected fish, and hepatic antioxidant capacity against peroxyl radicals (ACAP) levels, and superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR) activities were significantly inhibited. Dietary supplementation with 5% and 8% caffeine prevented the increase on hepatic ROS, LOOH and PC levels (except 5% caffeine) elicited by infection. Caffeine supplementation reduced or prevented the inhibition of hepatic SOD, GPx and GST activities. Finally, both caffeine concentrations reduced the hepatic microbial load compared to fish fed with control diets that were infected with A. hydrophila. Taken together, the data suggest that dietary supplementation with 8% caffeine may be considered a compelling prophylactic approach to aeromonosis caused by A. hydrophila.

Behavioural and biochemical effects of one-week exposure to aflatoxin B1 and aspartame in male Wistar rats

Food products are susceptible to contamination by mycotoxins, and aflatoxin B1 (AFB1) stands as the most toxic among them. AFB1 intoxication results in distinct signs, including widespread systemic toxicity. Aspartame (ASP) is an artificial sweetener used as a sugar substitute in many products, and compelling evidence indicates ASP can be toxic. Interestingly, mechanisms underlying ASP and AFB1 toxicity involve oxidative stress. In this context, concomitant use of ASP and AFB1 in a meal may predispose to currently unidentified behavioural and biochemical changes. Therefore, we evaluated the effect of AFB1 (250 μg/kg, intragastrically (i.g.)) and/or ASP (75 mg/kg, i.g.) exposure for 7 days on behavioural and biochemical markers of oxidative stress in male Wistar rats. AFB1 and/or ASP increased hepatic glutathione S-transferase (GST) activity when compared to controls. In the kidneys, increased GST activity was detected in AFB1 and AFB1+ASP groups. In addition, AFB1 and or ASP elicited behavioural changes in the open field, marble burying and splash tests, however no additive effects were detected. Altogether, present data suggest AFB1 and ASP predispose to anxiety- and obsessive-compulsive-like symptoms, as well as to enzymatic defence system imbalance in liver and kidney of Wistar rats.

The effect of Triaenophorus nodulosus (Cestoda: Bothriocephalidea) infection on some biochemical parameters of the liver of Perca fluviatilis.

Natural infection of 2 to 6-year-old perch with the cestode parasites Triaenophorus nodulosus was shown to have minor effects on the studied components of the antioxidant defense system, nucleic acids degradation, and carbohydrate metabolism enzymes in the liver of the fish. The level of infection of 1-4 parasite larvae per fish observed in wild population of perch was shown to be moderate in terms of its effect on the health of the host fish. The activity of hepatic enzymes β-galactosidase, β-glucosidase, cathepsin D, and glutathione S-transferase showed different responses in infected males and females, which indicates different potential resistance of fish to the stress exposure between genders.

Dietary quercetin abrogates hepatorenal oxidative damage associated with dichloromethane exposure in rats

Exposure to dichloromethane (DCM), a commonly used chlorinated solvent in industrial settings and for the production of many household products, reportedly elicits detrimental effects in animals and humans. The present study investigated the protective role of dietary quercetin on DCM-induced hepatorenal damage in rats. Experimental rats were orally administered with DCM (150 mg/kg) and 30 min later with quercetin at 10, 20 and 40 mg/kg or none for 7 consecutive days. The results indicated that DCM-mediated significant (p<0.05) increases in serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase and alkaline phosphatase activities as well as urea and creatinine levels were dose-dependently normalized to the control values in rats co-treated with quercetin. Further, quercetin co-treatment ameliorated DCM-mediated decrease in the hepatic and renal activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione S-transferase as well as glutathione level in the treated rats. Moreover, quercetin co-treatment markedly reduced lipid peroxidation level and protected against histological changes in liver and kidney of the treated rats. Taken together, quercetin abrogated hepatorenal oxidative damage in DCM-treated rats via improvement of antioxidant status and suppression of oxidative damage.

Short-term regulation of the hepatic activities of cytochrome P450 and glutathione S-transferase by nose-only cigarette smoke exposure in mice

The present study aimed to determine the effects of cigarette smoke on the regulation of hepatic cytochrome P450 (CYP) and glutathione S-transferase (GST) enzymes in male BALB/c mice exposed to nose-only cigarette smoke for 4 days. There were no significant increases in serum liver injury markers (alanine aminotransferase and aspartate aminotransferase) or oxidative stress (total antioxidant capacity, malondialdehyde, and glutathione disulfide/reduced glutathione) following cigarette smoke exposure, but malondialdehyde was elevated in the bronchoalveolar lavage fluid of smoke-exposed mice. Additionally, the hepatic microsomal protein levels of Cyp1a and Cyp2b, and the activities of ethoxyresorufin O-deethylase, pentoxyresorufin O-depenylase, and chlorzoxazone 6-hydrxylase, were elevated in smoke-exposed mice. Interestingly, the hepatic activities of GST toward 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene, and ethacrynic acid, but not cumene hydroperoxide were enhanced by cigarette smoke exposure, which was consistent with the increased expression levels of mu- and pi-class GSTs, but not alpha-class GSTs, observed in immunoblot analyses. These findings indicate that the short-term inhalation of cigarette smoke induces drug-metabolizing enzymes such as CYP1A, CYP2B, and mu/pi-class GSTs in the absence of hepatic injury and oxidative stress. Furthermore, smoking may alter hepatic drug metabolism, as well as the disposition and toxicity of xenobiotics, including some therapeutic drugs and cigarette smoke constituents.

The molecular and biochemical insight view of lycopene in ameliorating tramadol-induced liver toxicity in a rat model: implication of oxidative stress, apoptosis, and MAPK signaling pathways.

The influence of tramadol (TD) on hepatic tissue and the potential efficiency of lycopene to mitigate TD-induced hepatotoxic impacts were determined. Forty male albino rats were allocated into four groups: group I, untreated (placebo); group II, injected with TD (15mgkg-1) intraperitoneally (i.p.); group III, gastrogavaged with lycopene (10mgkg-1) per os (p.o.); and group IV received TD with lycopene with the same mentioned doses for 15days. The results demonstrated that TD induced augmentation in tissue lipid peroxidation biomarker and disturbance in the antioxidant homeostasis and elevated the activity of serum liver injury biomarkers and decreased serum protein, globulin, and albumin. Hepatic glutathione S-transferase (GST), superoxide dismutase (SOD), thioredoxin-1 (Txn-1), and catalase (CAT) activities and gene expression were decreased and glutathione content was reduced in the TD-challenged rats, and these effects were alleviated by lycopene. Furthermore, TD induced apoptosis in liver tissues as shown by DNA fragmentation and upregulation of proapoptotic Bax and Casp-3 while lycopene upregulated the antiapoptotic Bcl-2. The results of Western blot showed that lycopene initiated low expression of mitogen activated protein kinase pathway (MAPK) protein expression in liver tissues of TD-challenged rats. In addition, lycopene reduced fatty degeneration and necrosis of the liver in TD-challenged group. Our data demonstrate that lycopene appears to be highly efficient in mitigating the hepatotoxic impacts of TD by preventing lipid peroxidation and initiating modifications in the expression and activity of antioxidant pathways. Surprisingly, lycopene fortified liver tissue by inhibiting DNA fragmentation and apoptosis signaling induced by TD. MAPK activation may be dependent from ROS generation; due to lycopene which possessed antioxidant potential did have a substantial effect on MAPK activity.

Anti-arthritic properties of crude extract from Chenopodium ambrosioides L. leaves.

To evaluate the effect of hydroalcoholic crude extract (HCE) from Chenopodium ambrosioides leaves on the development of type II collagen-induced arthritis (CIA) and on pro-inflammatory cytokine balance. Collagen-induced arthritis was induced in DBA1/J mice. On the 21st day, the mice were treated orally with HCE or methotrexate, daily. Six weeks after beginning the treatment, the following measures were determined: lymphoid organs cell numbers, percentage of blood cells, IL-6, IFN-γ, TNF-α and IL-17 serum concentrations, activity of hepatic and kidney glutathione S-transferase, hepatic 7-ethoxyresorufin-O-deethylase activity, bone density and histopathology. Treatment of CIA mice with HCE 5mg/kg (HCE5) reduced the percentage of neutrophils and macrophages and the number of bone marrow cells and increased the lymphocyte numbers and the inguinal lymph node cellularity. This treatment inhibited the serum concentration of IL-6 and TNF-α, which may be related to the preservation of bone density and to the slight thickening of periarticular tissues, with minimal fibrosis and fibroblast proliferation in the joints. The CIA group presented advanced articular erosion and synovial hyperplasia. Phytochemical analysis showed mainly flavonols. HCE5 presented anti-arthritic potential and reduced IL-6 and TNF-α, which participate directly in the development and maintenance of the inflammatory process in rheumatoid arthritis.

Effects of dietary lipid-coated zinc on the antioxidant defense system in the small intestine and liver of piglets

The purpose of the study was to investigate the effects of lipid-coated ZnO (LCZ) and the level of LCZ compared with ordinary zinc oxide (ZnO) on antioxidant defense system in the intestine and liver of piglets. A total of forty piglets (n=8) were fed a diet supplemented with 100 ppm Zn with ZnO (ZnO-1), 2,500 ppm Zn with ZnO (ZnO-2), 100 ppm Zn as LCZ (LCZ-1), 200 ppm Zn as LCZ (LCZ-2), or 400 ppm Zn as LCZ (LCZ-3) for 14-d, respectively. The LCZ-3 group resulted in higher (P<0.05) mRNA expressions and activities of CuZn-superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), and glutathione S-transferase (GST) in jejunal mucosa compared with the ZnO-1 and LCZ-1 groups, while no difference was observed in the mRNA level of antioxidant genes between the ZnO-1 and ZnO-2 groups. Within the LCZ groups, the LCZ level linearly and quadratically (P<0.01) increased antioxidant enzymes in the jejunum. The maximum response of jejunal antioxidant enzymes to Zn supplementation was achieved by 400 ppm of LCZ. Hepatic mRNA expression of antioxidant enzymes was unaffected by Zn source and level, while hepatic SOD and GST activities were greater (P<0.05) in the LCZ-3 group than in the ZnO-1 group. No difference was observed in lipid peroxidation of the jejunum and liver and the total antioxidant power of plasma among groups. In conclusion, a supplementation with 400 ppm of LCZ resulted in a maximum increase in antioxidant enzymes, indicating that LCZ may affect antioxidant defense system more profoundly than ZnO.

Feeding higher level of de-oiled rice bran causes stress to Labeo rohita fingerlings

A 60-day feeding trial was conducted with different inclusion levels of de-oiled rice bran (DORB) to study the digestive enzyme activity, physio-metabolic changes and oxidative stress in Labeo rohita fingerlings. Six iso-nitrogenous (30% crude protein), iso-lipidic (6% crude lipid) and iso-energetic (380.14Kcal/100g) semi-purified diets were prepared with the graded levels of DORB viz. 0 (control), T20 (20%), T30 (30%), T40 (40%), T50 (50%) and T60 (60%). Three hundred and fifteen (315) fingerlings with an average weight of 8±0.5g were distributed randomly in seven treatments in triplicates, following a completely randomised design (CRD). The digestive enzyme, protease and amylase activities were higher in 20, 30 and 40% DORB fed groups but the Lipase activity did not vary significantly whereas, SOD and GST activity was significantly lower (p<0.05) in the same groups. The T50 and T60 groups showed significantly higher (p<0.05) hepatic LDH (Lactate dehydrogenase), GST (Glutathione-s-transferase) and SOD activity, while RBC (Red blood cell) and WBC (White blood cell) content were found significantly lower in these groups. The catalase activity did not vary significantly (p>0.05) among treatment group. Serum glucose content was higher in the T40, T50 and T60 groups, while serum total protein, albumin, NBT (Nitroblue tetrazolium) and haemoglobin levels were not significantly different among the treatments. From the study, it can be concluded that DORB causes stress to fish when fed at higher inclusion level (50 & 60%).

Herba Gelsemii elegantis is detoxified by ramulus et folium Mussaendae pubescentis extract by modulating hepatic cytochrome P450 and glutathione S-transferase enzymes in rats.

Herba Gelsemii elegantis (GE) has been frequently used as a Chinese folk medicine but has high acute toxicity. In Traditional Chinese Medicine, it may be detoxified by Ramulus et Folium Mussaendae pubescentis (MP), but the detoxification mechanism has remained elusive. The present study aimed to evaluate the detoxification mechanisms by which MP modulates the effect of GE in rats, including the inhibition of hepatic cytochrome P (CYP)450 and glutathione S-transferase (GST) enzymes. Male Sprague Dawley rats were orally administered GE at three doses (0.36, 0.43 or 0.54 g/kg) alone and, at the highest dose, in combination with MP (21.6 g/kg) every day for 7 consecutive days. The control group of animals received the same volume of saline. The mRNA and protein expression of hepatic CYPs representative of two subfamilies (CYP2E1 and CYP1A2) were separately assessed by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), western blot and immunohistochemistry assays. The mRNA and protein expression as well as enzyme activity of hepatic GST were assessed by RT-qPCR, western blot and colorimetric assays, respectively. The results indicated that GE significantly inhibited CYP2E1 mRNA and protein expression in a dose-dependent manner. Co-administration of MP increased CYP2E1 mRNA and protein expression as compared with the high GE dose alone. Cells expressing CYP2E1, located around the hepatic vascular plexus under a clear background, were identified by immunohistochemical staining. The results for CYP1A2 were similar to those for CYP2E1. At all concentrations used, GE significantly inhibited GST mu 1 (GSTm1) mRNA and protein expression in a dose-dependent manner, as compared with the control. Combination of GE and MP increased the mRNA and protein expression of GSTm1 as compared with the high dose of GE. However, the differences in GST-pi mRNA and protein expression between the GE and GE + MP groups were not significant. Of note, rats co-treated with MP were significantly protected from the decrease in GST activity produced by GE. The present study indicated that co-administration of GE and MP upregulated the activities of CYP450 and GST enzymes when compared with GE alone. This modulation may explain for the effect of MP in reducing the acute toxicity of GE.

Pear pomace water extract suppresses hepatic lipid peroxidation and protects against liver damage in rats fed a high fat/cholesterol diet.

The protective effect of pear pomace water extract (PPWE) against hepatic lipid peroxidation was investigated in rats fed a 41% kcal fat diet containing 0.21% cholesterol (HFCD). For 5weeks, 200 or 400mg/kg of PPWE was administrated once daily via oral gavage. Body weights were lower in the PPWE-treated group than in the control group. Serum total antioxidant capacity increased, whereas hepatic thiobarbituric acid reactive substances significantly decreased after the administration of PPWE. PPWE recovered the HFCD-induced reduction of hepatic glutathione S-transferase and glutathione peroxidase activity. The serum alanine aminotransferase and aspartate aminotransferase activities significantly decreased on PPWE treatment. The present investigation suggests that PPWE represents a valuable natural antioxidant source for use in the health food industry.