Glutathione S-transferase Activity In Liver Research Articles

Consumption of toxic benthic cyanobacteria by two common demersal fish: Growth, antioxidant and liver histopathology responses

Benthic freshwater cyanobacteria have the potential to produce toxins. Compared with more extensively studied plankton species, little is known about the impact of harmful benthic cyanobacteria on aquatic organisms. As demersal fish are usually in direct contact with benthic cyanobacteria, it is important to understand their interactive effects. This study investigated the physio-chemical responses of two demersal fish (Xenocypris davidi and Crucian carp) after exposure to benthic Oscillatoria (producing cylindrospermopsin, 2 × 106 cells/mL) for 7 days. Interestingly, benthic Oscillatoria had less adverse effects on X. davidi than C. carp. The two demersal fish effectively ingested Oscillatoria, but Oscillatoria cell sheathes could not be fully digested in C. carp intestines and led to growth inhibition. Oscillatoria consumption induced oxidative stress and triggered alterations in detoxification enzyme activities in the X. davidi liver. Superoxide dismutase (SOD) and glutathione reductase (GR) activities significantly increased in the C. carp liver, but catalase (CAT) and detoxification enzymes glutathione S-transferase (GST) and glutathione (GSH) activities were insignificantly changed. This suggested that C. carp may have a relatively weak detoxification capacity for toxic Oscillatoria. Oscillatoria ingestion led to more pronounced liver pathological changes in C. carp, including swelling, deformation, and loss of cytoskeleton structure. Simultaneously, fish consumption of Oscillatoria increased extracellular cylindrospermopsin concentration. These results provide valuable insights into the ecological risks associated with benthic cyanobacteria in aquatic ecosystems.

Supplementation with grape seed extract, onion peel extract, or rosemary extract in the diet alleviates growth inhibition, liver damage, and oxidative stress induced by diquat in Lohmann chicks

The present study aimed to assess the impact of grape seed extract (GSE), onion peel extract (OPE), and rosemary extract (ROE) on Diquat-induced growth restriction and oxidative stress in Lohmann chicks. A total of 200 chicks were randomly assigned to 5 diets: the positive control (PC) group, the negative control (NC) group, GSE group, OPE group, and ROE group. During the first 7 d of trial, compared with NC and PC groups, the GSE group enhanced average daily feed intake (ADFI). From day 8–21, diquat injection resulted in reduced growth performance, increased platelet volume distribution width (PWD), malondialdehyde (MDA) concentration, and activities of alanine aminotransferase (ALT) in chick serum; it also decreased total protein (TP), albumin (ALB), globulin (GLB) concentration, activities of superoxide dismutase (SOD) and glutathione S-transferase (GST) in chick serum; furthermore, it increased MDA concentration while decreasing GST activities in liver. The NC group exhibited lower average daily gain (ADG) than other groups. Compared with NC group, GSE group reduced ALT activities, MDA levels, and red cell distribution width (RDW), and PDW concentration; it also increased SOD, GST activities. The ROE group lowered ALT activities and MDA concentration. The OPE group decreased ALT activities, and MDA levels, RDW, and PDW concentration, and increased SOD activities of chicks. These results suggest that supplementing antioxidants in diets alleviated oxidative stress in chicks challenged by improving antioxidant capacity and liver function.

The transient character of mitochondrial uncoupling by the popular fungicide fluazinam is specific for liver

The popular fungicide fluazinam is known to exhibit an unusual cyclic pattern of the protonophoric uncoupling activity in isolated rat liver mitochondria (RLM), with membrane deenergization followed by spontaneous recoupling in the minute scale, which is associated with glutathione conjugation of fluazinam catalyzed by glutathione-S-transferase (GST). Here, we compare the fluazinam effect on RLM with that on rat kidney (RKM) and heart (RHM) mitochondria by monitoring three bioenergetic parameters: oxygen consumption rate, mitochondrial membrane potential and reduction of nucleotides. Only in RLM, the uncoupling activity of fluazinam was transient, i.e. disappeared in a few minutes, whereas in RKM and RHM it was stable in this time scale. We attribute this difference to the increased activity of mitochondrial GST in liver. We report data on the detection of glutathione-fluazinam conjugates by mass-spectrometry, thin layer chromatography and capillary electrophoresis after incubation of fluazinam with RLM but not with RKM, which supports the assumption of the tissue specificity of the conjugation.

CONSUMPTION OF BROCCOLI SPROUTS INCREASED THE ACTIVITY OF GLUTATHIONE-DEPENDENT ANTIOXIDANT ENZYMES IN MURINE LIVER

Aim. The purpose of this work was to investigate effects of the consumption of broccoli sprouts on the activity of antioxidant defense enzymes in the liver of. GPx isoforms. After photo fixation of gels, we determined activity of each isoform densitometrically using ImageJ software. Results were statistically analyzed by ANOVA followed by post-hoc Tukey's test. Data are presented as mean±SEM. Methods. Frozen tissue was homozeniged in lysis buffer, centrifuged and resulted supernatants were used for analysis. Activities of enzymes were determined by using electrophoresis in polyacrylamide gel. After electrophoresis we conducted dyeing of separate gels for detection of superoxide dismutase (SOD), glutathione-S-transferase (GST) or glutathione peroxidase (GPx) isoforms. After photo fixation of gels, we determined activity of each isoform densitometrically using ImageJ software. Results were statistically analyzed by ANOVA followed by post-hoc Tukey's test. Data are presented as mean±SEM. Results. In the hepatic tissue of all four groups of mice, two isoforms of SOD (SOD1 and SOD2) were detected in gels. The intensity of the bands of both isoforms was not significantly different between groups. Three isoforms of GST (GST1, GST2, GST3) were detected in the liver samples. The activity of GST1 did not significantly differ between the experimental groups. Activities of GST2 and GST3 forms were significantly higher in the group “Broccoli” compared to Control and Cafeteria Diet groups. We identified three isoforms of glutathione peroxidase (GPx1, GPx2, GPx3) in liver samples. The activity of GPx isoform 1 was not significantly different between the experimental groups. The activity of GPx2 was significantly higher in the group of mice that consumed Broccoli and Cafeteria Diet + Broccoli compared to Control. GPx2 activity was significantly higher in the Broccoli group compared to the Cafeteria Diet group. Activity of GPx3 was significantly higher in the Broccoli group compared to the Control and Cafeteria Diet group. Conclusions. Cafeteria diet did not significantly affect the activity of SOD isoforms, but led to redistribution of in the activity of GST and GPx isoforms in murine liver. Feeding with broccoli spouts significantly increased the activity of 2 and 3 isoforms of GST and GPx in murine liver compared to values in control mice and mice fed with cafeteria diet. Combination of Broccoli + Cafereria diet had small activating effects on antioxidant enzyme acivity, compared with cafeteria diet.

Effects of white mustard (Sinapis alba) oil on growth performance, immune response, blood parameters, digestive and antioxidant enzyme activities in rainbow trout (Oncorhynchusmykiss)

A study was conducted to evaluate the effects of dietary supplementation of white mustard (Sinapis alba) oil (WMO) on growth performance, immune responses, digestive and antioxidant enzyme activities in juvenile rainbow trout (Oncorhynchus mykiss). For this purpose, fish (initial weight: 25.77 ± 0.13 g) were divided into four experimental groups in triplicate and fed ad libitum twice a day with diets containing WMO at 0 (control), 0.5, 1, and 1.5% of diet for 9 weeks. Three fish from each tank (n:9 per treatment) were sampled on 21st, 42nd, and 63rd days for further analyses. At the end of the feeding period, fish were challenged with Aeromonas hydrophila and Yersinia ruckeri in two separate experimental setups. Results showed that final weight, weight gain, and specific growth rate were significantly increased in all experimental groups compared to the control. Feed conversion ratio was similar among treatments. Respiratory burst and potential killing activity decreased in all experimental groups compared to the control (P < 0.05). Lysozyme and myeloperoxidase activities were elevated in all experimental groups at the end of the experiment compared to the control (P < 0.05). Cytokine gene expressions in the head kidney and intestine were elevated in all experimental groups compared to that of the control in general (P < 0.05). Hematological responses of the experimental fish groups were similar to that of the control (P > 0.05). Pepsin and trypsin levels decreased in all experimental groups (P < 0.05). In terms of antioxidant enzyme activities, significant improvement in liver superoxide dismutase, catalase, and glutathione s-transferase activities in all treatment groups were determined (P < 0.05). In addition, a significant decline in liver lipid peroxidation levels was recorded in all treated groups at all sampling times compared to the control (P < 0.05). At the end of this feeding trial, no significant differences (P > 0.05) were observed in survival against A. hydrophila among experimental groups compared to the control (P > 0.05). However, increased survival against Y. ruckeri was determined in experimental fish groups (P < 0.05). This study suggests that white mustard oil had a favorable effect on the overall health and growth of rainbow trout.

Effects of dietary pantothenic acid on growth, antioxidant ability and innate immune response in juvenile black carp

An 8-week feeding study was conducted to examine how dietary pantothenic acid (PA) affects growth, antioxidant ability and innate immunity in juvenile black carp (Mylopharyngodon piceus). Juvenile fish (7.35 ± 0.06 g) were fed diets with PA at 0, 5, 10, 20, 40 and 80 mg/kg, respectively. The highest weight gain (WG), specific growth rate (SGR) and protein efficiency ratio (PER) were obtained with 10 mg/kg dietary PA (p < 0.05), as well as the lowest feed conversion ratio (FCR). Adequate dietary PA (10 and 20 mg/kg) markedly upregulated neuropeptide Y (NPY), orexin (ORX) and ghrelin (GRL) and downregulated cholecystokinin (CCK) in the brain of these animals (p < 0.05). Intestinal sodium-dependent multivitamin transporter (SMVT) expression and α amylase, trypsin, chymotrypsin and lipase activities were all improved after supplementation of PA at 10 or 20 mg/kg (p < 0.05). In addition, adequate dietary PA (10 and 20 mg/kg) significantly increased the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR), as well as the amounts of reduced glutathione (GSH) and total antioxidant capacity (T-AOC) in the liver of these animals (p < 0.05). Meanwhile, liver glutathione S-transferase (GST) activity and malondialdehyde (MDA) amounts levels were both markedly decreased with dietary PA at 10 or 20 mg/kg (p < 0.05). Furthermore, adequate dietary PA significantly elevated the mRNA amounts of NFE2-related nuclear factor 2 (Nrf2) and downregulated Kelch-like-ECH-associated protein 1a (Keap1a) and Keap1b (p < 0.05), and remarkably upregulated innate defense molecules, including lysozyme (LYZ), natural resistance-associated macrophage protein (NRAMP), liver-expressed antimicrobial peptide 2 (LEAP-2), hepcidin (HEPC), complement 3 (C3) and complement 9 (C9) in the liver (p < 0.05). Meanwhile, elevated dietary PA resulted in increased LYZ activity and C3 content and decreased aspartate aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum samples from juvenile black carp compared with the groups fed PA-deficient diets (p < 0.05). Moreover, 10, 20 and 40 mg/kg PA-containing diets starkly downregulated intestinal interleukin 8 (IL-8) and IL-11 at the mRNA level in comparison with the PA-deficient diet (0 mg/kg) (p < 0.05). However, PA supplementation at 10, 20 or 40 mg/kg resulted in increased intestinal zonula occludens-1 (ZO-1), ZO-2, ZO-3, claudin 3, claudin 4, claudin 8, claudin 15 and occludin mRNA levels in M. piceus in comparison with the 0 mg/kg PA group (p < 0.05). Jointly, the above findings suggested adequate dietary PA (10 and 20 mg/kg) enhances feed utilization and growth performance, as well as antioxidant capacities and non-specific immune reactions in juvenile M. piceus.

The effects of dietary exposure to Magnéli phase titanium suboxide and titanium dioxide on rainbow trout (Oncorhynchus mykiss)

Magnéli phase titanium suboxides (Magnéli TiOx) are promising, novel materials with superior properties compared to TiO2, they are substoichiometric titanium oxides with the chemical formula TinO2n-1 (where n ≥ 1). In this study, for the first time, subchronic effects of dietary intake of Magnéli TiOx were evaluated and compared with TiO2 particles of similar size, in concentrations 0.1% and 0.01% of feed. The experiment consisted of 38 d of an exposition period and 14 d of a depuration period. Minor effects on plasma biochemical profile and morphological parameters were recorded. A reduced count of leukocytes was found in the blood of both Magnéli TiOx and TiO2 exposed fish, suggesting immunotoxic effects. Erythrocytosis was specific for Magnéli TiOx. Indices of oxidative stress, namely increased lipid peroxidation in liver, increased activity of superoxide dismutase in liver, kidney and gills and glutathione S-transferase (GST) in gills, as well as decreased activity of ceruloplasmin and GST in liver were found predominantly in fish exposed to TiO2. Histopathological examination revealed increased lipid-like vacuolation in the liver, the presence of hyaline droplets in renal tubules and multiplication of mucous glands in the epidermis in both tested substances and intestine damage in TiO2 groups.Overall, in Magnéli TiOx exposed groups, fewer adverse effects compared to TiO2 expositions were recorded. Their wider practical implementation in place of TiO2 is therefore beneficial.

Boric acid supplementation affects antioxidant activity in ovariectomized female rats

This study aimed to investigate the protective effect of boric acid (BA) supplementation against oxidative stress (OS) in ovariectomized rats. A total of 48 nonpregnant female Wistar albino rats (180-250 g) were used in the experiment. The rats were divided into six equal groups (n = 8): Control, OVX, OVX + 5 mg/kg BA (OVX + BA5), OVX + 10 mg/kg BA (OVX + BA10), 5 mg/kg BA (BA5), and 10 mg/kg BA (BA10). The rats were intraperitoneally anesthetized with a combination of ketamine hydrochloride (85 mg/kg) and xylazine (10 mg/kg) and underwent a bilateral ovariectomy. Supplementation with 5 mg/kg and 10 mg/kg BA via oral gavage was started 2 weeks after ovariectomy and continued for 20 days. Catalase (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione (GSH), and malondialdehyde (MDA) levels in the liver, kidney, and brain tissues of rats were analyzed by the spectrophotometric method. MDA concentrations in the liver tissue was increased in the OVX rats compared to the control group (p &lt;0.05). Liver GST activity was significantly decreased in the OVX rats, but it was increased with 5 mg/kg and 10 mg/kg BA supplementation (p &lt;0.05). Mean kidney GSH, GPx, and CAT activities in the OVX rats were increased with 5 mg/kg and 10 mg/kg BA supplementation (p &lt;0.05). In the brain tissue, GST activity was increased in the OVX rats treated with 10 mg/kg BA (p &lt;0.05). These results indicate that BA supplementation can enhance antioxidant defense mechanisms against OS after ovariectomy in female rats.

A typical enzyme activity for glutathione conjugation indicates exposure of pacu to pollutants

Abstract Functional enzyme assays to detect sublethal poisoning of Neotropical fish are paramount. Accordingly, we assayed a glutathione S-transferase (GST) activity in liver and kidney cytosols from Piaractus mesopotamicus injected with methyl parathion or benzo[a]pyrene using the substrate 1-chloro-2,4-dinitrobenzene (CDNB), which is the usual substrate for assaying a known general activity of GST. Since the most reactive substrate is required to reveal specific changes in enzyme activity, we also used two alternative substrates, 1,2-dichloro-4-nitrobenzene (DCNB) and ethacrynic acid (ETHA). Activities with CDNB or ETHA did not change. However, assays with DCNB showed that methyl parathion caused a decrease in GST activity in the liver on the 24th, 48th and 96th hour after the injection. DCNB also revealed that GST activity in the liver increased seven days after benzo[a]pyrene injection, coming down to normal after fourteen days. Benzo[a]pyrene, but not methyl parathion, increased the activities with DCNB in cytosol from the kidney seven and fourteen days after the injection. Thus, a decreased liver GST activity assayed with DCNB corresponded to contamination of P. mesopotamicus with methyl parathion. The increase of this GST activity in the liver and the kidney correlates to pacu contamination with polycyclic aromatic hydrocarbons.

Sesame lignans upregulate glutathione S-transferase expression and downregulate microRNA-669c-3p.

Oxidative stress is associated with aging and pathologies such as cardiovascular diseases, Alzheimer’s disease, and cancer. Glutathione S-transferase (GST), a family of detoxification enzymes, plays a crucial role in countering oxidative stress. Therefore, there is a need for the development of physiologically functional foods and agricultural products, which enhance GST activity. Sesamin and episesamin are major lignans in refined sesame oil that exhibit beneficial properties including antioxidative stress effects. A previous study showed that sesamin upregulated GST activity. This study aimed to elucidate the mechanism underlying the GST activity enhancement elicited by sesame lignans. C57BL/6J mice were orally administered 20 mg/kg body weight sesame lignans (sesamin:episesamin=1:1) for 7 days. Oral administration of sesame lignans increased the GST activity in the mouse liver. Furthermore, the lignans upregulated GSTA1, GSTA4, and GSTM4 protein expression. Microarray analysis revealed that sesame lignans changed the expression of various microRNAs (miRNAs) (84 upregulated, 19 downregulated). We also found 16 miRNAs, including miR-669c-3p, that may negatively regulate GST expression among the 19 miRNAs with reduced expression caused by the sesame lignans. miR-669c is reportedly negatively correlated with GST. Additionally, we transfected NMuLi cells with an miR-669c-3p mimic and evaluated the effect of miR-669c-3p on GST mRNA and protein expressions. The results showed that the miR-669c-3p mimic suppressed the mRNA and protein levels of GSTA4 and GSTM4. In conclusion, sesame lignans increased GST protein expression and activity and downregulated miRNAs, including miR-669c-3p, which is a possible suppressor of GST.

Effects of melatonin and N-acetylcysteine on aluminum phosphide poisoning in rats.

Aluminum phosphide (ALP) poisoning is one of the deadliest types of poisoning in the world. The antioxidant properties of melatonin and N-acetylcysteine and their effects on reducing cell death have been identified. The aim of this study was to evaluate the effects of N-acetylcysteine and melatonin in the treatment of aluminum phosphide poisoning in rats. Fifty male Wistar rats weighing 200-250 g were tested in five groups of ten. The first group was the control group; the second group received (10 mg/kg) of ALP, the third group received (10 mg/kg) of ALP and (10 mg/kg) of melatonin, the fourth group received (10 mg/kg) of ALP and (10 mg/kg) of N-acetylcysteine, and the last group received (10 mg/kg) of ALP and (10 mg/kg) of melatonin and N-acetylcysteine. The plasma of samples was isolated, and the activity of antioxidant enzymes (glutathione S-transferase (GST), Superoxide dismutase (SOD), and catalase (CAT)) was analyzed. The concentrations of CAT, GST, Glutathione, GSH were decreased in plasma, liver, and kidneys of mice treated with aluminum phosphide; also, the concentrations of aspartate aminotransferase (AST), ALT, and AlK were increased (P < 0.05), while the activity of SOD did not change significantly (P > 0.05). Treatment with N-acetylcysteine and melatonin led to an increase in the activity of CAT, GST, and GSH in plasma, liver, and kidney. After the administration of N-acetylcysteine and melatonin to mice, the levels of all enzymes were close to normal, and the mice survived for 12-15 hours after administration. The administration of N-acetylcysteine (NAC) and melatonin at a dose of 10 mg/kg improves hepatic manifestations and prevents liver necrosis; also, they are considered potential therapeutic agents in the treatment of this poisoning.

Cucurbituril Ameliorates Liver Damage Induced by Microcystis aeruginosa in a Mouse Model.

Microcystis aeruginosa is a cyanobacterium that produces a variety of cyclic heptapeptide toxins in freshwater. The protective effects of the macromolecular container cucurbit[7]uril (CB7) were evaluated using mouse models of cyanotoxin-induced liver damage. Biochemical analysis of liver function was performed to gauge the extent of liver damage after exposure to cyanobacterial crude extract [CCE; LD50 = 35 mg/kg body weight; intraperitoneal (i.p.)] in the absence or presence of CB7 (35 mg/kg body weight, i.p.). CCE injection resulted in liver enlargement, potentiated the activities of alanine aminotransferase (ALT) and glutathione S-transferase (GST), increased lipid peroxidation (LPO), and reduced protein phosphatase 1 (PP1) activity. CCE-induced liver enlargement, ALT and GST activities, and LPO were significantly reduced when CB7 was coadministered. Moreover, the CCE-induced decline of PP1 activity was also ameliorated in the presence of CB7. Treatment with CB7 alone did not affect liver function, which exhibited a dose tolerance of 100 mg/kg body wt. Overall, our results illustrated that the addition of CB7 significantly reduced CCE-induced hepatotoxicity (P < 0.05).

Evaluation of toxicity and response of African catfish (Clarias gariepinus) exposed to manganese chloride solution

This study investigated the acute toxicity and behavioural response of African catfish (Clarias gariepinus) to manganese chloride (MnCl ) solution. One hundred (100) pieces of juvenile Clarias gariepinus were acclimatized 2 for 14 days in ten (10) plastic bowls containing 25 L of water each. The acute-toxicity of manganese chloride, LC and sub chronic exposure (28 days) were investigated. For sub-lethal exposure; fifty pieces of C. gariepinus 50 were divided into five groups of ten in bowls labelled (A to E). The fish in groups (A to D) were exposed to manganese chloride solutions at: 68.5, 137, 205.5 and 274 mg/L respectively while group G served as the control. On day 28, the exposed fish were sacrificed; blood, muscle, liver, and gills were collected for haematological and histological studies. The activities of the superoxide dismutase (SOD) and glutathione-Stransferase (GST) were determined using standard methods. The manganese concentrations in the liver, gills and muscle tissues were determined using Atomic Absorption Spectrophotometer (AAS). The LC obtained 50 was 2.74 g/L. The mean water temperature showed that there was no significant variation at (p &lt; 0.05) between the control and other groups. The results of growth parameters showed that fish exposed to 137 mg/L manganese concentration had better growth performance than those exposed to higher concentrations. The activities of SOD and GST in the liver of fish increased significantly (p &lt; 0.05) as manganese concentration increases. The red blood cells concentrations decreases while white blood cells increases as the concentration of manganese increases respectively. The mean bioaccumulation of manganese in the organs of C. gariepinus followed the order of liver &gt; gill &gt; muscle. The histopathological study revealed alterations in the liver, gill and muscle tissues. This study concluded that manganese at concentration greater than 137 mg/L elicits adverse effect on C. gariepinus growth performance, haematology, histopathology as well as liver SOD and GST activities.&#x0D; Key words: Behavioural response, Cat-fish, Juvenile, Manganese chloride, Toxicity

Antioxidant activities of aqueous and ethyl acetate fractions of Daucus carota L. seed against triton X-100 induced oxidative stress in mice

Daucus carota seed is medicinally useful in the management of disease such as diabetes mellitus, which is associated with oxidative stress. This study investigated the phytochemical constituents, in vitro and in vivo antioxidant activities of aqueous fraction (AQF) and ethyl acetate fraction (EAF) of D. carota seed in triton X-100 induced oxidative stress. The fractions were obtained by partitioning aqueous extract of the seed in ethyl acetate. Oxidative stress was induced by intraperitoneal injection of triton X-100, after oral administration of the fractions in mice. The results revealed the presence of alkaloids, tannins and phenolics in AQF and EAF. AQF and EAF demonstrated significant in vitro antioxidant activities comparable to butylated hydroxytolune (BHT) with IC50 values of 0.30, 0.38 and 0.92 mg/ml respectively for DPPH scavenging activities. Induction of oxidative stress by triton X-100 caused increased malondialdehyde concentration in plasma and liver of experimental mice, which was significantly decreased (p<0.05) in the plasma of mice pre-administered with AQF and EAF. No significant change (p>0.05) was observed in the nitric oxide level in mice treated with AQF and EAF compared with triton X-100 control. The fractions caused a significant decrease (p<0.05) in plasma activities of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) but no significant alteration (p>0.05) in plasma glutathione peroxidase (GPx) and glutathione-S-transferase (GST). The pre-administration also resulted in decreased SOD and increased GPx (p<0.05) in the liver, but no significant alteration (p>0.05) in liver GST activity and GSH concentration. The results revealed that AQF and EAF of D. carrot seed possesses phytochemicals, which could be responsible for the enhancement of antioxidant defense system in vivo and alleviation of triton X-100 induced oxidative stress.

The toxicological effect of dietary excess of saccharicterpenin, the extract of camellia seed meal, in piglets

Recently, saccharicterpenin extracted from Camellia oleifera seed meal has become a widely used feed supplement in animal husbandry. In order to assess its safety, this study was designed to investigate the toxicity and histopathological effects of saccharicterpenin on piglets. One hundred-fifty weaned pigs ((Yorkshire×Landrace)×Duroc), 75 males and 75 females with body weight (BW) of (7.35±0.29) kg, were randomly allotted to groups receiving diets supplemented with 0, 500, 1 000, 2 500 or 5 000 mg kg−1 saccharicterpenin for 70 d. The diet with 500 mg kg−1 saccharicterpenin supplementation improved liver glutathione peroxidase (GSH-Px) activity, and the diet with 1 000 mg kg−1 saccharicterpenin supplementation improved liver glutathione S-transferase (GSH-S) activity in piglets on d 70 (P<0.05). At 2 500 mg kg−1, saccharicterpenin in the diets reduced average daily feed intake (ADFI) and average daily gain (ADG) of piglets from d 1 to 35, damaged the cardiac tissue and liver on d 35, and decreased white blood cell counts (WBC), activities of catalase (CAT) and GSH-Px, and concentrations of glucose (GLU) and urea nitrogen (BUN) in the blood of piglets on d 70 (P<0.05). In addition, diets with 5 000 mg kg−1 saccharicterpenin supplementation reduced ADFI, ADG and increased diarrhea rates of piglets from d 36 to 70, and decreased hemoglobin (HGB) concentration and activity of CAT in the blood of piglets on d 70 (P<0.05). Moreover, at a rate of 5 000 mg kg−1, saccharicterpenin supplementation increased pancreas index on d 35 and hepatic index on d 70, and damaged cardiac tissue, liver and spleen during the whole experimental period (P<0.05). These results suggested that dietary 500 mg kg−1 saccharicterpenin supplementation had beneficial effects on piglets, but excessive supplementation (2 500 or 5 000 mg kg−1) of saccharicterpenin in the diets could lead to growth retardation, hematological abnormalities and organ injuries.

Assessment of the effects of atrazine, dichlorodiphenyltrichloroethane, and dimethoate on freshwater fish (Oreochromis mossambicus): a case study of the A2 farmlands in Chiredzi, in the southeastern part of Zimbabwe.

A study was carried out to assess the levels and effects of atrazine, dimethoate, and dichlorodiphenyltrichloroethane on freshwater fish (Oreochromis mossambicus). Water and fish were sampled once from a dam within the Hippo Valley A2 farmlands in Chiredzi, in the southeastern part of Zimbabwe. The samples were screened for atrazine, dimethoate, and dichlorodiphenyltrichloroethane (DDT), the pesticides commonly used in the region. Atrazine and dimethoate are pesticides commonly used in the control of weeds and pests in the agricultural production of sugarcane in Hippo Valley, Chiredzi region. The effects of the pesticides on biochemical endpoints of the sampled fish were determined. The analyzed biochemical end parameters were superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase activities in liver and white muscle fish extracts. Dichlorodiphenyltrichloroethane was observed in water and fish muscle tissue at concentrations of 131.3 μg/l and 171.7 μg/kg, respectively, while atrazine was detected at concentrations of 6.15 μg/l and 142.0 μg/kg in water and fish muscle tissue, respectively. The observed concentrations of atrazine and DDT in water samples were above the limits permissible by the World Health Organization in drinking water. Dimethoate was found in concentrations of 4.21 μg/l and 1.30 μg/kg in water and fish muscle tissue respectively. The observed concentration of dimethoate in water was below the acceptable limit set by the Guidelines for Canadian Drinking Water. Antioxidant enzyme activities were increased significantly (p < 0.05) in fish exposed to water from Hippo Valley, Chiredzi, when compared with the controls. The enhanced activities of the studied antioxidant enzyme system were attributed to exposure to pollutants in the water body. Alterations of the biochemical integrity of fish indicate negative effects of the pesticides on the well-being of fish and undoubtedly other aquatic biota as well.

Developmental differences in the expression of ABC transporters at rat brain barrier interfaces following chronic exposure to diallyl sulfide

Many pregnant women and prematurely born infants require medication for clinical conditions including cancer, cardiac defects and psychiatric disorders. In adults drug transfer from blood into brain is mostly restricted by efflux mechanisms (ATP-binding cassette, ABC transporters). These mechanisms have been little studied during brain development. Here expression of eight ABC transporters (abcb1a, abcb1b, abcg2, abcc1, abcc2, abcc3, abcc4, abcc5) and activity of conjugating enzyme glutathione-s-transferase (GST) were measured in livers, brain cortices (blood-brain-barrier) and choroid plexuses (blood-cerebrospinal fluid, CSF, barrier) during postnatal rat development. Controls were compared to animals chronically injected (4 days, 200 mg/kg/day) with known abcb1a inducer diallyl sulfide (DAS). Results reveal both tissue- and age-dependent regulation. In liver abcb1a and abcc3 were up-regulated at all ages. In cortex abcb1a/b, abcg2 and abcc4/abcc5 were up-regulated in adults only, while in choroid plexus abcb1a and abcc2 were up-regulated only at P14. DAS treatment increased GST activity in livers, but not in cortex or choroid plexuses. Immunocytochemistry of ABC transporters at the CSF-brain interface showed that PGP and BCRP predominated in neuroepithelium while MRP2/4/5 were prominent in adult ependyma. These results indicate an age-related capacity of brain barriers to dynamically regulate their defence mechanisms when chronically challenged by xenobiotic compounds.

RNA-sequencing to assess the health of wild yellow perch (Perca flavescens) populations from the St. Lawrence River, Canada

This study aimed to better understand in situ cumulative effects of anthropogenic stressors on the health of St. Lawrence River (QC, Canada) yellow perch populations using high-throughput transcriptomics and a multi-biological level approach. Fish were collected in the upstream fluvial Lake Saint-François (LSF) with low degree of environmental perturbations; Lake Saint-Louis (LSL) considered having a moderate degree of anthropogenic stressors, and Lake Saint-Pierre (LSP) a sector where the perch population has been severely declining. Morphometric results indicated that fish from the downstream LSP showed lower body condition compared to LSF and LSL. Liver transcriptomic responses were assessed by RNA-sequencing. Two hundred and eighty genes were over-transcribed in LSP perch while 200 genes were under-transcribed compared to LSF and LSL. In LSP fish, genes transcripts related to reproduction, retinol, iron, thyroid hormones, oxidative stress, lipid metabolism and immune functions were among the most abundant suggesting that multiple metabolic and physiological pathways were impacted by environmental stressors at this site. Inhibition of liver superoxide dismutase, catalase and glutathione S-transferase activities were also observed at the cellular level. Overall, identified impacted biological pathways in perch from LSP may help understand the precarious state of this population and identify the factors inhibiting its recovery.

Dietary optimal reduced glutathione improves innate immunity, oxidative stress resistance and detoxification function of grass carp (Ctenopharyngodon idella) against microcystin-LR

The present study reports on the effects of dietary glutathione (GSH) on non-specific immunity, oxidative stress resistance and detoxification in grass carp (Ctenopharyngodon idella) infected with microcystins. Six hundred and thirty juvenile grass carp with initial body weight of (5.10 ± 0.09) g were randomly distributed into six groups with three replicates each and stocked in 18 tanks (35 fish per tank), fed six diets containing graded levels of GSH for 60 days. At the end of the feeding trial, ten fish per tank were selected and injected intraperitoneally with 200 μg/kg body weight (BW) dose of pure microcystin-LR (MC-LR). The results showed that, at 0 h, 24 h of MC-LR injection, with the increase of dietary GSH content, serum lysozyme, alkaline phosphatase (ALP) and complement 3 (C3) levels, the activities and mRNA expression levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in liver, and liver GSH content increased first and then decreased (P < 0.05). When dietary GSH content was 407.45 mg/kg diet, these parameters reached the highest levels (P < 0.05), and in the same dose of GSH group, in addition to lysozyme activity at 24 h was significantly higher than that at 0 h, the other indicators at 24 h were significantly lower than those before exposure (at 0 h) (P < 0.05). In contrast, serum cortisol and glucose, and liver reactive oxygen species (ROS) and malondialdehyde (MDA) contents decreased first and then increased (P < 0.05), when dietary GSH content was 407.45 mg/kg diet, the above parameters reached the lowest levels (P < 0.05), and in the same dose of GSH group their contents at 24 h were significantly higher than those before exposure (P < 0.05). In addition, before MC-LR exposure, the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had no significant difference of all groups (P > 0.05), liver glutathione S-transferase (GST) and its mRNA expression levels had a rising trend while liver glutathione reductase (GR) activities significantly decreased and then maintained a lower level with dietary GSH content increasing (P < 0.05). At 24 h of MC-LR injection, serum ALT and AST activities decreased at first and then increased while liver GST and GR activities and their mRNA expression levels increased first and then decreased (P < 0.05). Therefore, the basal diet supplemented with GSH 407.45 mg/kg could improve innate immunity, antioxidant stress ability and detoxification function of grass carp against MC-LR exposure. However, dietary excess GSH might promote oxidation, resulting in negative effect.

Toxic Effects and Depuration on the Antioxidant and Neurotransmitter Responses after Dietary Lead Exposure in Starry Flounder.

Starry Flounder Platichthys stellatus were exposed to dietary lead (Pb) at concentrations of 0, 30, 60, 120, and 240mg/kg for 4weeks. Recover period was conducted for 2weeks after the exposure. Exposure to Pb concentrations over 60mg/kg induced significant changes in the antioxidant responses in the liver, kidney, and gill and continued even after the depuration period in the liver (over 120mg/kg for superoxide dismutase [SOD] activity) and kidney (at 240mg/kg for glutathione [GSH] levels). Glutathione S-transferase (GST) activity in liver, kidney, and gill were increased by dietary Pb exposure, and recovery was observed in all groups during the recovery period. Acetylcholinesterase (AChE) activity was significantly inhibited in the brain and muscle of flounder at Pb exposure over 120mg/kg, and no restoration was observed after the depuration period. Lysozyme activity in the plasma was significantly increased at Pb exposures greater than 60mg kg but was restored after the depuration period. The results of this study indicate that dietary Pb exposure induces toxic effects on antioxidant responses, neurotransmitter, and immune responses of Starry Flounder.