GST Expression Research Articles

Protective and therapeutic effects of sildenafil and tadalafil on aflatoxin B1-induced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has been classified as one of the most common forms of liver cancer occurring worldwide, and risk factors include hepatitis B & C virus, alcoholism, and dietary carcinogens like aflatoxin B1 (AFB1), which is produced by fungus Aspergillus flavus and Aspergillus parasiticus. Metabolism of AFB1 resulted into the formation of AFB1-exo-8, 9-epoxide which is largely responsible for HCC development. So far conventional cytotoxic chemotherapy has not provided much benefit in HCC, necessitating the need for newer treatment modalities. Recent reports suggest that phosphodiesterase-5 inhibitors (PDE5i) may have anticancer activity, but till date, the anticancer property of PDE5i (tadalafil & sildenafil) has not been evaluated in HCC. The present study was aimed to define the anticancer property of tadalafil and sildenafil against AFB1-induced HCC rats. Rats were randomly divided into five groups with five rats in each group. Except normal control group, rats of all other groups were fed with 5% alcohol via drinking water for 3weeks. After 3weeks, two successive dose of AFB1 (1mg/kg bw, ip) was administered on subsequent days followed by the administration of PDE5i (tadalafil & sildenafil, 10mg/kg bw) along with drinking water after 6weeks of treatment with AFB1 for 2weeks. An in-depth investigation into its mechanistic aspect revealed that development of HCC induced by aflatoxin B1, decreased the mRNA expression and activity of antioxidant enzyme SOD, GPx, catalase, GR and GST, and GSH content with a concomitant increase in the level of lipid peroxidation. Post-treatment with PDE5 inhibitor (tadalafil & sildenafil) restored the above parameters towards normal, and this result was more effective in case of sildenafil. Thus, results from the above studies suggest that PDE5 inhibitors may act as anticancer agents by preventing the development and progression of HCC by modulating the key parameters of antioxidant pathway.

Antagonistic Potential of Novel Endophytic Bacillus Strains and Mediation of Plant Defense against Verticillium Wilt in Upland Cotton.

Verticillium wilt caused by Verticillium dahliae is a threatening disease of cotton, causing economic loss worldwide. In this study, nine endophytic Bacillus strains isolated from cotton roots exhibited inhibitory activity against V. dahliae strain VD-080 in a dual culture assay. B. altitudinis HNH7 and B. velezensis HNH9 were chosen for further experiments based on their high antagonistic activity. The secondary metabolites of HNH7 and HNH9 also inhibited the growth of VD-080. Genetic marker-assisted detection revealed the presence of bacillibactin, surfactin, bacillomycin and fengycin encoding genes in the genome of HNH7 and HNH9 and their corresponding gene products were validated through LC-MS. Scanning electron microscopy revealed mycelial disintegration, curling and shrinkage of VD-080 hyphae after treatment with methanolic extracts of the isolated endophytes. Furthermore, a significant reduction in verticillium wilt severity was noticed in cotton plants treated with HNH7 and HNH9 as compared to control treatments. Moreover, the expression of defense-linked genes, viz., MPK3, GST, SOD, PAL, PPO and HMGR, was considerably higher in plants treated with endophytic Bacillus strains and inoculated with VD-080 as compared to control.

Chlorella sp. modulates the glutathione mediated detoxification and S-adenosylmethionine dependent methyltransferase to counter arsenic toxicity in Oryza sativa L.

The present study investigates the role of Chlorella sp. in the mitigation of arsenic (iAs) induced toxicity in Oryza sativa L. The study shows, co-culture of rice seedlings with Chlorella sp. reduced the iAs accumulation, simultaneously improving the growth of seedlings under iAs treatments. While treatment with As(III) and As(V) (60 µM) alone, inflicted toxicity in rice seedlings, manifested as significant enhancement in stress markers levels (TBRAS and H2O2), this coincided with the shifting of cellular reduced state to oxidized state (reduced GSH/GSSG ratio). Contrarily, co-culturing rice seedlings with Chlorella sp. under iAs toxicity, reduced these stress markers and recovered the GSH/GSSG ratio. The GSH dependent antioxidant enzymes i.e. GR and GPX activities also exhibited significant enhancement upon co-culturing rice seedlings with Chlorella sp. against iAs stress. Simultaneously, the expression of four thiol dependent GRX genes, i.e. GRX13950, GRX35340, GRX12190 and GRX07950 were enhanced against As(III) and As(V) (60 µM), which reduced upon co-culturing with Chlorella sp. A similar trend was also observed with the expression of GST genes, where the co-culture with Chlorella sp. significantly reduced the genes expression of two isoforms (GST 38600 and GST 38610). On the contrary, the expression of S-adenosylmethionine dependent methyltransferases (SAMT) gene in rice seedlings was enhanced upon co-culturing with the Chlorella sp. against iAs stress. Overall, the results demonstrate that the rice seedlings when co-culture with Chlorella sp. ameliorates iAs toxicity through GSH dependent detoxification pathway, evident from the enhanced expression of GRX, GST, SAMT genes and activity of GSH dependent antioxidant enzymes (GR and GPX) in the rice seedlings.

Effect of pollution with lead, cupper, cadmium on gene expression pattern of liver GST and serum lysozymes in Nile tilapia (Oreochromis. niloticus)

Objective: This study was conducted to evaluate the influence of pollution with lead, copper, cadmium on the gene expression pattern of liver Glutathione-S-transferase and serum lysozyme in Nile tilapia (Oreochromis. niloticus). Design: Descriptive study. Fish: A Total of 120 Nile tilapia fish (Oreochromis niloticus) samples were collected from Lake Manzala, and drainage water at different localities. Procedures: Cd, Cu, and Pb concentrations residues within mid-dorsal muscle tissue, within gills, liver, and kidney were determined. Erythrocyte count, hemoglobin concentration, Packed Cell volume and other blood indices, as well as, total leukocyte count were measured. Biochemically, Alanine transaminase, Aspartate transaminase activities, total protein, creatinine, uric acid, lysozymes activity were estimated. GST gene expression was determined in the liver. Results: The results showed that Pb, Cu and Cd were bio accumulated at a higher level in the liver, kidney and gills of Nile tilapia fish (Oreochromis niloticus) from all sampling sites. The levels of the ALT and AST were increased, total protein and Albumin concentrations were decreased. Creatinine and uric acid were significantly (P≤ 0.05) increased in all groups (compared to the control group. Hematological parameters and lysozyme activity were decreased. Up regulation of the hepatic GST expression levels in Nile tilapia exposed to the heavy metals in comparison to the control value. Conclusion and clinical relevance: This study shows that lead, copper and cadmium were bio accumulated at higher concentration in liver, kidney, gills and muscles of Nile tilapia due to large industrial activities near locations of the sampling sites. Additionally, GST gene expression represents sensitive biomarker of aquatic pollution.

Effect of pollution with lead, cupper, cadmium on gene expression pattern of liver GST and serum lysozymes in Nile tilapia (Oreochromis. niloticus)

Objective: This study was conducted to evaluate the influence of pollution with lead, copper, cadmium on the gene expression pattern of liver Glutathione-S-transferase and serum lysozyme in Nile tilapia (Oreochromis. niloticus). Design: Descriptive study. Fish: A Total of 120 Nile tilapia fish (Oreochromis niloticus) samples were collected from Lake Manzala, and drainage water at different localities. Procedures: lead, copper and cadmium concentrations within mid-dorsal muscle tissue, within gills, liver, and kidney were determined. Erythrocyte count, hemoglobin concentration, Packed Cell volume and other blood indices, as well as, total leukocyte count were measured. Biochemically, Alanine transaminase, Aspartate transaminase activities, total protein, creatinine, uric acid, lysozymes activity were estimated. GST gene expression was determined in the liver. Results: The results showed that Pb, Cu and Cd were bio accumulated at a higher level in the liver, kidney and gills of Nile tilapia fish (Oreochromis niloticus) from all sampling sites. The activities of ALT and AST were increased significantly (p < 0.05), but total protein and Albumin concentrations were decreased. Creatinine and uric acid were significantly increased in all groups compared to the control group (P≤ 0.05). Hematological parameters and lysozyme activity were decreased. Up regulation of the hepatic GST expression levels in Nile tilapia exposed to the heavy metals in comparison to the control value. Conclusion and clinical relevance: This study shows that lead, copper and cadmium were bio accumulated at higher concentration in liver, kidney, gills and muscles of Nile tilapia due to large industrial activities near locations of the sampling sites. Additionally, GST gene expression represents sensitive biomarker of aquatic pollution.

The Effects of Amoxicillin, Cefazolin, and Gentamicin Antibiotics on the Antioxidant System in Mouse Heart Tissues.

Free radicals lead to destruction in various organs of the organism. The improper use of antibiotics increases the formation of free radicals and causes oxidative stress. In this study, it was aimed to determine the effects of gentamicin, amoxicillin, and cefazolin antibiotics on the mouse heart. 20 male mice were divided into 4 groups (1st control, 2nd amoxicillin, 3rd cefazolin, and 4th gentamicin groups). The mice in the experimental groups were administered antibiotics intraperitoneally at a dose of 100 mg / kg for 6 days. The control group received normal saline in the same way. The gene expression levels and enzyme activities of SOD, CAT, GPx, GR, GST, and G6PD antioxidant enzymes were investigated. GSH levels decreased in both the amoxicillin and cefazolin groups, while GR, CAT, and SOD enzyme activities increased. In the amoxicillin group, Gr, Gst, Cat, and Sod gene expression levels increased. As a result, it was concluded that amoxicillin and cefazolin caused oxidative stress in the heart, however, gentamicin did not cause any effects.

Combined effects of exposure to engineered silver nanoparticles and the water-soluble fraction of crude oil in the marine copepod Calanus finmarchicus

While it is likely that ENPs may occur together with other contaminants in nature, the combined effects of exposure to both ENPs and environmental contaminants are not studied sufficiently. In this study, we investigated the acute and sublethal toxicity of PVP coated silver nanoparticles (AgNP) and ionic silver (Ag+; administered as AgNO3) to the marine copepod Calanus finmarchicus. We further studied effects of single exposures to AgNPs (nominal concentrations: low 15 μg L−1 NPL, high 150 μg L−1 NPH) or Ag+ (60 μg L−1), and effects of co-exposure to AgNPs, Ag+ and the water-soluble fraction (WSF; 100 μg L−1) of a crude oil (AgNP + WSF; Ag++WSF). The gene expression and the activity of antioxidant defense enzymes SOD, CAT and GST, as well as the gene expression of HSP90 and CYP330A1 were determined as sublethal endpoints. Results show that Ag+ was more acutely toxic compared to AgNPs, with 96 h LC50 concentrations of 403 μg L−1 for AgNPs, and 147 μg L−1 for Ag+. Organismal uptake of Ag following exposure was similar for AgNP and Ag+, and was not significantly different when co-exposed to WSF. Exposure to AgNPs alone caused increases in gene expressions of GST and SOD, whereas WSF exposure caused an induction in SOD. Responses in enzyme activities were generally low, with significant effects observed only on SOD activity in NPL and WSF exposures and on GST activity in NPL and NPH exposures. Combined AgNP and WSF exposures caused slightly altered responses in expression of SOD, GST and CYP330A1 genes compared to the single exposures of either AgNPs or WSF. However, there was no clear pattern of cumulative effects caused by co-exposures of AgNPs and WSF. The present study indicates that the exposure to AgNPs, Ag+, and to a lesser degree WSF cause an oxidative stress response in C. finmarchicus, which was slightly, but mostly not significantly altered in combined exposures. This indicated that the combined effects between Ag and WSF are relatively limited, at least with regard to oxidative stress.

Duration-dependent effects induced by titanium dioxide nanoparticles on pancreas of adult male albino rats (histological and biochemical study)

ABSTRACT Titanium dioxide nanoparticles (TiO2NPs) have been widely used in numerous applications and enter the human body through different routes. This study aimed to investigate the effect of intraperitoneal TiO2NPs on the histological and biochemical structure of rat pancreas. Fifty adult male albino rats were divided into four groups. Group I (control) was equally divided into two subgroups. Groups II, III, and IV: rats received intraperitoneal TiO2NPs for 7, 14, and 45 days, respectively. Blood samples were taken for the estimation of blood glucose, serum insulin, serum α-amylase, and lipase activity levels. Sections of the pancreas were processed for light, electron microscope examination, and immunohistochemical detection of insulin protein. Other parts were exposed to Real-Time Polymerase Chain Reaction for Bax, Bcl-2, SOD, and GST mRNA gene expression. Results showed pancreatic tissue damage, including acinar and islet cells, which became worse with increased duration of exposure to TiO2NPs. Decreased immune expression of the insulin protein together with decreased serum insulin and increased blood glucose levels indicated the alteration of β cells. Decreased serum α-amylase and lipase activities indicated alteration of acinar cells. Increased Bax and decreased Bcl-2 mRNA expression levels showed the apoptotic effect of TiO2NPs caused by oxidative stress and evidenced by a significant reduction in the mRNA expression of SOD and GST in a duration-dependent manner. In conclusion: the present study stated that TiO2NPs exposure for long durations had toxic effects on both exocrine and endocrine pancreas mediated by apoptotic and oxidative stress pathways.

Microplastics Aggravate the Bioaccumulation of Two Waterborne Veterinary Antibiotics in an Edible Bivalve Species: Potential Mechanisms and Implications for Human Health.

Edible bivalves are one of the major types of seafood and may be subject to antibiotic and microplastics (MPs) coexposure under realistic scenarios. However, the effect of MPs on the bioaccumulation of antibiotics in edible bivalves and subsequent health risks for consumers remain poorly understood. Therefore, the bioaccumulation of two frequently detected veterinary antibiotics, oxytetracycline (OTC) and florfenicol (FLO), with or without the copresence of MPs was investigated in the blood clam. Health risks associated with the consumption of contaminated clams were also assessed. Furthermore, the activity of GST and expression of key detoxification genes were analyzed as well. The bioaccumulation of OTC and FLO in clams was found to be aggravated by MPs. Because the estimated target hazard quotients (THQs) were far less than the critical value, direct toxic effects of consuming contaminated clams are negligible. However, the dietary exposure doses of the human gut microbiota (DEGM) to the antibiotics tested were greater than or similar to corresponding minimum selective concentrations (MSC), indicating a potential antibiotic resistance risk. Moreover, the GST activity and expression of detoxification genes were significantly suppressed by MPs, suggesting that the disruption of detoxification represents one possible explanation for the aggravated bioaccumulation observed here.

Evaluation of boscalid toxicity on Daphnia magna by using antioxidant enzyme activities, the expression of genes related to antioxidant and detoxification systems, and life-history parameters

Boscalid is a succinate dehydrogenase inhibitor fungicide commonly used to control a range of plant pathogens. Although it is one of the most common fungicides in the aquatic environment, the potential adverse effects of boscalid on freshwater invertebrates still remain unclear. This study aimed to evaluate the toxicity of boscalid on Daphnia magna (D. magna) and provide new information to assess the eco-toxicity of the boscalid on aquatic invertebrates. The effects of boscalid on malondialdehyde (MDA) level, activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) and the mRNA level of genes associated with antioxidant system (sod, cat, and gst) and detoxification (cytochrome P450 4 (cyp4) and nuclear respiratory factor 1 (nrf1)) were determined after 48 h treatment. The effect of boscalid on reproduction and development of D. magna was evaluated by a 21-d-chronic toxicity test. Boscalid dose-dependently altered activities of SOD, CAT, and GST and led to lipid peroxidation during acute exposure in D. magna. Exposure to 5 and 10 mg/L boscalid also significantly decreased gene expression of sod, gst, cyp4 and nrf1 but increased cat gene expression. Furthermore, chronic toxicity results showed that exposure to boscalid decreased molting frequency, number of neonates per Daphnia, and the number of broods per female as compared to the control groups. The above results indicated that boscalid had significant negative impacts on D. magna, and information present here helps to evaluate the eco-toxicity caused by boscalid on aquatic invertebrates.

Effects of Antimony on Reactive Oxygen and Nitrogen Species (ROS and RNS) and Antioxidant Mechanisms in Tomato Plants.

This research studies the effects that Sb toxicity (0.0, 0.5, and 1.0 mM) has on the growth, reactive oxygen and nitrogen species, and antioxidant systems in tomato plants. Sb is accumulated preferentially in the roots, with little capacity for its translocation to the leaves where the concentration is much lower. The growth of the seedlings is reduced, with alteration in the content in other nutrients. There is a decrease in the content of Fe, Mg, and Mn, while Cu and Zn increase. The contents in chlorophyll a and b decrease, as does the photosynthetic efficiency. On the contrary the carotenoids increase, indicating a possible action as antioxidants and protectors against Sb. The phenolic compounds do not change, and seem not to be involved in the defense response of the tomato against the stress by Sb. The water content of the leaves decreases while that of proline increases in response to the Sb toxicity. Fluorescence microscopy images and spectrofluorometric detection showed increases in the production of O2.–, H2O2, NO, and ONOO–, but not of nitrosothiols. The Sb toxicity induces changes in the SOD, POX, APX, and GR antioxidant activities, which show a clear activation in the roots. In leaves, only the SOD and APX increase. The DHAR activity is inhibited in roots but undergoes no changes in the leaves, as is also the case for the POX and GR activities. Ascorbate increases while GSH decreases in the roots. The total AsA + DHA content increases in the roots, but the total GSH + GSSG content decreases, while neither is altered in the leaves. Under Sb toxicity increases the expression of the SOD, APX, and GR genes, while the expression of GST decreases dramatically in roots but increases in leaves. In addition, an alteration is observed in the pattern of the growth of the cells in the elongation zone, with smaller and disorganized cells. All these effects appear to be related to the ability of the Sb to form complexes with thiol groups, including GSH, altering both redox homeostasis and the levels of auxin in the roots and the quiescent center.

Effects of imidacloprid on the oxidative stress, detoxification and gut microbiota of Chinese mitten crab, Eriocheir sinensis

Imidacloprid (IMI) is used in integrated aquaculture systems for pest control and the toxicity of IMI to non-target aquatic animals such as fish and microcrustaceans has been recognised. However, knowledge about the toxic effect of IMI on commercial crabs is still scarce. In the present study, effects of IMI on the acute toxicity, antioxidative status, detoxification systems and gut microbiota in Chinese mitten crab, Erocheir sinensis were investigated. In the present study, the 96-h LC50 of IMI for E. sinensis was 24.97 mg/L. Under sublethal exposure, superoxide dismutase (SOD) activities increased under low concentration (LC, 5 μg/L) and median concentration (MC, 50 μg/L) exposure, but decreased in high concentration group (HC, 500 μg/L). Activities of catalyse (CAT) decreased in a dose-dependent manner. Detoxification-related enzymes aminopyrine N-demethylase (APND) and erythromycin N-demethylase (ERND) increased in all treatments whereas glutathione-S-transferase (GST) decreased dose-dependently. The relative mRNA expression of the cytochrome P4502 (cyp2) gene was induced significantly in LC and HC groups while no significant change was observed in cytochrome P4503 (cyp3) gene. The expression of gst was also significantly decreased in HC group. Up-regulation of heat shock protein hsp70 and 90 was observed in MC and HC groups whereas hsp60 up-regulated only in LC group. In addition, significant changes of composition of microbial communities at both phylum and genus levels were found in this test. In particular, beneficial bacteria were found to decrease and pathogens increased after exposure to IMI. These results indicate that high concentration of IMI could induce oxidative stress and suppress the detoxification system mainly by down-regulation of gst mRNA expression, inhibition of enzyme activities and dysbiosis of gut microbiota.

Dietary nanoencapsulated quercetin homeostated transcription of redox-status orchestrating genes in zebrafish (Danio rerio) exposed to silver nanoparticles

The present study assessed the protective effect of chitosan-nanoencapsulated quercetin (Qu-ChiNPs) against oxidative stress caused by silver nanoparticles (AgNPs). To this end, the transcription of prime genes regulating hepatic Keap1-Nrf2 pathway as well as downstream antioxidant enzymes were monitored prior to and after oxidative stress by AgNPs. Zebrafish (Danio rerio; n = 225) was assigned into five experimental groups based on feeding with diets supplemented with different additives as follows: negative and positive control groups, without additive; ChiNPs, 400 mg nanochitosan per kg diet; Quercetin, 400 mg free quercetin per kg diet; and Qu-ChiNPs, 400 mg Qu-ChiNPs per kg diet. At the end of the feeding trial (40 days), the experimental groups, except the negative control, were exposed to sublethal concentration of AgNPs (0.15 mg L−1) for 96h. Before exposure to AgNPs, free quercetin-treated diet significantly upregulated Keap1, Nrf2, Cat, SOD, GPx, and GST genes in the liver tissue when compared with the control diet, whereas Qu-Chi.NPs downregulated their transcription to the lowest levels. After exposure to AgNPs, all genes exhibited different responses in the AgNPs-exposed groups. The highest transcription of Nrf2, Cat, SOD, GPx, and GST was observed in the positive group, with being upregulated about 8, 10, 8, 8, and 7 times, respectively, when compared to the respective ones in the negative control. However, Keap1 showed a reverse response with being transcripted 12 times lower. The quercetin treatments, especially Qu-Chi.NPs, significantly reduced the transcription of Nrf2, Cat, SOD, GPx, and GST genes, yet enhanced Keap1 expression. Qu-Chi.NPs reduced the expression of Nrf2, SOD, Cat, GPx, and GST about 11, 10, 15, 10, and 10 times, respectively, yet increased that of Keap1 about 12 times. Taken together, nanoencapsulation can improve the antioxidant efficacy of quercetin against AgNPs toxicity and might reduce involvement of the cellular antioxidant system through tuning redox status. More broadly, it would be interesting to assess the effects of Qu-Chi.NPs against other metallic and organic oxidative stressors or pollutants.

Moringa Oleifera Leaf Extract Repairs the Oxidative Misbalance following Sub-Chronic Exposure to Sodium Fluoride in Nile Tilapia Oreochromis niloticus.

Simple SummaryThe present study investigated the antioxidant effect of ethanolic extract of Moringa Oleifera (MO) leaves against sodium fluoride-induced toxicity in Nile tilapia. It is concluded that MO leaves are a promising antioxidant plant via downregulation of lipid peroxidation, and upregulation of antioxidant enzyme activity including SOD, CAT, GPx, GSH, and TAC in liver, kidney, gills, and muscle tissue in a time-dependent manner, in addition to downregulation of mRNA expression of antioxidant-related genes.The potential antioxidant property of Moringa oleifera (MO) has been the recent focus of an increased number of studies. However few studies investigated its antioxidative ability against sodium fluoride-induced redox balance breakdown in Oreochromis niloticus. Thus, this study evaluates the effects of MO against the oxidative stress induced by sub-chronic exposure to sodium fluoride (NaF). A total of 264 fish (40 ± 3 g BW) were used to calculate the 96 hr-LC50 of NaF and perform the sub-chronic exposure study. 96 hr-LC50 of NaF was calculated as (61 mg/L). The 1/10 dose of the calculated 96 hr-LC50 (6.1 mg/L) was used to complete the sub chronic exposure for eight weeks. Fish were divided into four groups (n = 51; three replicates each); control, non-treated group; NaF group (exposed to NaF 6.1 mg/L); MO group (treated with 1% MO of diet); and NaF+MO (exposed to NaF 6.1 mg/L and treated with 1% MO of diet). The results revealed that the sub-chronic exposure to NaF (6.1 mg/L) was substantially increased malondialdehyde (MDA) and decrease the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reduced (GSH), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) in the gills, liver, kidney, and muscle tissue in a time-dependent manner. In addition, a significant reduction in mRNA expression of GST in the liver was reported following NaF exposure. On the contrary, dietary supplementation of MO to NaF-exposed fish resulted in a significant reduction in MDA levels, and a significant elevation of SOD, CAT, GSH, GPx, and TAC activities in a time-dependent manner, in addition to significant elevation of GST mRNA expression in liver tissue. It could be concluded that a 1% MO (w/w) ration is a promising antioxidant plant that may successfully use to interfere with the oxidation processes induced by NaF in various tissues of Oreochromis niloticus.

Glutathione transferase and mammary tumors

The analysis of publications from the last 5 years is presented in this review. These articles describe the relationship of glutathione transferase (GST) with mammary tumors. Most of these works are dedicated to investigating the genotypic relationship between GST and neoplasms in human. The most common are single nucleotide polymorphism of GSTP1 Val105Ile (rs1695) and gene deletions GSTM1 and GSTT1. Several publications describe polymorphisms of GSTM3(rs4970737), GSTM4 and GSTA5. These polymorphisms (especially GSTP1 Val105Ile) are associated with the risk of mammary tumors, overall survival and relapse in patients of some ethnic groups. This is as a result of reduced enzymatic activity of GST and disturb of ability to detoxify substrates. Some studies demonstrate that single nucleotide polymorphism of GSTP1 Val105IIe is associated with a better response to chemotherapy and overall survival of patients, but no association with genotypes of GSTM1 and GSTT1. The injections of carcinogenic compounds into the tissue of mammary gland or its feeding to rats leed to decrease of GST activity and to development of tumors. The increased expression of GST in breast cancer cell lines leeds to increase of the resistance of these cells against various chemical compounds therefore the enzyme catalyzes the binding of these compounds to glutathione and this prevent their negative effects and is necessary for the formation of conjugates. Such increased expression of GST indicates on the resistance of breast cancer cell lines in particular to the action of drugs, which reduces their therapeutic effect. This is shown on cell lines BT474, MCF-7, MCF-7/ADR, MCF-7/ADR-1024, MCF-10A, MDA-MB-231, MDA-MB-468 and T47D. Chemical compounds (including antitumor drugs), that reduce the activity and/or expression of GST, can have a cytotoxic effect on these cells. Mammary tumors associated with epigenetic changes that do not change the sequence of nucleotides in GST genes. The methylation of the GSTP1 promoter decreases an expression of protein in mammary tissue and increases a risk of cancer in different ethnic groups. Compounds increase the level of expression of genes when they are able to lower the level of methylation or to affect demethylation. Polymorphisms of GST genes, their association with response to chemotherapy and overall survival of patients, expression of GST and it dependence on the action of anticancer drugs, methylation of GST promoter are associated with diagnosis, prognosis, and treatment of mammary neoplasms.

Mechanism of protection of rat hepatocytes from acetaminophen-induced cellular damage by ethanol extract of Aerva lanata.

The aim of this study is to evaluate the protective effect of ethanol extract of Aerva lanata (EEAL) in preventing acetaminophen induced liver toxicity. EEAL was prepared and its hepatoprotective effect was studied in both isolated primary hepatocytes in vitro and in Sprague Dawley rats in vivo. For in vivo studies, the animals were grouped as Group I – Control; Group II – ACN (2 g/kg b.w.); Group III – EEAL (50 mg/kg b.w.) + ACN (2 g/kg b.w.), Group IV – EEAL (100 mg/kg b.w.) + ACN (2 g/kg b.w.). Extracellular activities of the enzymes liver aminotransferease (GOT, GPT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in isolated hepatocytes and rat plasma were studied colorimetrically. Expression of GST, Nrf2, COX 1 & COX2 genes in rat liver were evaluated by RT-PCR. The results showed that ACN induced down-regulation of Nrf2 and upregulation of GST gene expression, which were modulated by EEAL treatment. GOT, GPT, ALP and LDH levels were found to be lowered in both hepatocyte culture media and plasma following EEAL treatment. In addition, the medium GOT and GPT levels were diminished following EEAL treatment only. Moreover, only ALP and LDH in serum appeared to be at normal level following EEAL treatment, whereas GOT and GPT showed levels lower than control. ACN treatment increased the expression of pro-inflammatory COX 1 and COX 2 genes and the levels of these genes were reduced by EEAL treatment. EEAL pre-treated rats exposed to ACN were found to retain normal hepatic structure compared to ACN alone treated rats. From these results it can be concluded that ethanol extract of A. lanata possesses both anti-inflammatory and hepatoprotective activity.

Dietary curcumin enhances intestinal antioxidant capacity in ducklings via altering gene expression of antioxidant and key detoxification enzymes.

The study investigated the effects of dietary curcumin supplementation on tissue distribution of curcumin and its metabolites, intestinal antioxidant capacity, and expression of detoxification-related genes in ducks. A total of 720 one-day-old male Cherry Valley Pekin ducklings (initial BW 58.6 ± 0.1g) were randomly assigned to 4 dietary groups each with 6 replicates of 30 ducks using a single factorial arrangement design. Ducks in the control group were fed a basal diet and the remainder were fed the basal diet supplemented with 200, 400, or 800mg/kg curcumin. The experiment lasted for 21 D. Curcumin was present at 13.12 to 16.18mg/g in the cecal digesta, 75.50 to 575.40μg/g in jejunal mucosa, 35.10 to 73.65μg/g in liver, and 7.02 to 7.88μg/mL in plasma. The jejunal and hepatic contents of curcumin increased significantly (P < 0.05) in response to supplementation with 400 and 800mg/kg of curcumin respectively, compared with 200mg curcumin/kg group. There was a linear (P < 0.001) effect of dietary curcumin on relative abundance of SOD1, GPX1, CAT, HO-1, and Nrf2 transcripts, and a quadratic (P < 0.001) increase in the activities of GSH-Px and T-AOC in jejunal mucosa. The expression of CYP1A4, CYP2D17 increased and CYP1B1, CYP2A6 decreased linearly (P < 0.001) with dietary curcumin concentrations. In addition, dietary curcumin increased gene expression of GST, MRP6, and ABCB1 in jejunal mucosa. In conclusion, dietary supplementation with 200 to 800mg/kg curcumin enhanced the accumulation of curcumin and its metabolites in jejunum as well as increasing the antioxidant capacity and detoxification potential, which play major roles in the protection of duck intestines against damage.

Characterization of rat glutathione transferases in olfactory epithelium and mucus

The olfactory epithelium is continuously exposed to exogenous chemicals, including odorants. During the past decade, the enzymes surrounding the olfactory receptors have been shown to make an important contribution to the process of olfaction. Mammalian xenobiotic metabolizing enzymes, such as cytochrome P450, esterases and glutathione transferases (GSTs), have been shown to participate in odorant clearance from the olfactory receptor environment, consequently contributing to the maintenance of sensitivity toward odorants. GSTs have previously been shown to be involved in numerous physiological processes, including detoxification, steroid hormone biosynthesis, and amino acid catabolism. These enzymes ensure either the capture or the glutathione conjugation of a large number of ligands. Using a multi-technique approach (proteomic, immunocytochemistry and activity assays), our results indicate that GSTs play an important role in the rat olfactory process. First, proteomic analysis demonstrated the presence of different putative odorant metabolizing enzymes, including different GSTs, in the rat nasal mucus. Second, GST expression was investigated in situ in rat olfactory tissues using immunohistochemical methods. Third, the activity of the main GST (GSTM2) odorant was studied with in vitro experiments. Recombinant GSTM2 was used to screen a set of odorants and characterize the nature of its interaction with the odorants. Our results support a significant role of GSTs in the modulation of odorant availability for receptors in the peripheral olfactory process.

Correction to: CYP2E1-mediated oxidative stress regulates HO-1 and GST expression in maneb- and paraquat-treated rat polymorphonuclear leukocytes.

In the original publication of the article, the wrong β-actin blots were pasted in Figs. 1b and 2c. The correct versions of Figs. 1b and 2c are given in this correction.

Ex vivo and in vivo effects of arsenite on GST and ABCC2 activity and expression in the middle intestine of the rainbow trout Oncorhynchus mykiss

In fish of freshwaters environments, the accumulation and toxic effects of arsenite (AsIII) can be attenuated by detoxification proteins such as GST and ABCC transporters. We studied the effects of AsIII on the middle intestine of O. mykiss in ex-vivo and in vivo/ex vivo assays. For the ex vivo assays, we measured the transport rate of the ABCC substrate DNP-SG and GST activity in intestinal strips and everted sacs. AsIII inhibited DNP-SG transport in a concentration-dependent manner, specifically when we applied it on the basolateral side. GST activity increased when we applied a maximum concentration of AsIII. For the in vivo/ex vivo assays, we kept fish in water with or without 7.7 μmol L−1 of AsIII for 48 h. Then, we measured DNP-SG transport rate, GST activity, and PP1 activity in intestine strips during one hour. For PP1 activity, we incubated the strips with or without microcystin-LR (MCLR), a toxin excreted through ABCC2 proteins. We also analyzed Abcc2 and Gst-π mRNA expression in intestine and liver tissue. In the group exposed in vivo to AsIII, DNP-SG transport rate and GST activity were higher and the effect of MCLR over PP1 activity was attenuated. AsIII significantly induced only Abcc2 mRNA expression in both middle intestine and liver. Our results suggest that, in the middle intestine of O. mykiss, AsIII is absorbed mainly at the basolateral side of the enterocytes, excreted to the lumen by ABCC2 transporters, and is capable of modulating Abcc2 mRNA expression by a transcriptional mechanism.