Glutathione S-transferase Research Articles

Transcriptome reanalysis and gene expression of 13 detoxification genes for avermectin and pyridaben resistance in Panonychus citri

Citrus red mites (P. citri) are key pests affecting citrus production worldwide due to pesticide resistance. The resistance mechanisms of ten pesticides are known, but a comprehensive study using transcriptome data is missing. This study employed deeptools, cuffdiff, rmats, bcftools and other software to examine gene expression variation, alternative splicing (AS), and mutations in mite resistance. The research highlighted that pesticides can regulate gene transcription, and red mites with resistance increase cytochrome P450, glutathione S-transferases, carboxylesterase, and acetylcholinesterase expression. Pyridaben also induces new AS events. Fluazinam-induced mites show mRNA splicing peaking earlier than transcription, both peaking at one day and returning to baseline after two days. AS profiles are similar in different mite populations with overlapping pesticide resistances. Lastly, specific mitochondrial SNPs in mites might mediate resistance against select pesticides.

Glutathione s-transferase pi is a marker of loop diuretic resistance in patients with congestive heart failure exacerbation

Abstract Background Loop diuretic resistance (LDR) in patients with heart failure (HF) exacerbation is associated with worse clinical outcomes, greater symptom burden and mortality. Diagnosis and treatment of LDR remains a significant clinical dilemma. Purpose To assess the ability of different urine biomarkers to predict LDR in patients with HF exacerbation. Methods Consecutive patients with congestive HF exacerbation were prospectively included in the study. HF was diagnosed according to ESC 2021 HF Guidelines definition. Congestion was defined as a presence of one or more of the following signs: edema, ascites, pleural effusion. LDR was defined as persistent congestion on the 4th day of hospital stay despite high i.v. loop diuretic dose. Urine biomarkers released from different parts of the nephron (Kidney Injury Molecule-1 - KIM-1, N-acetyl-β-D-glucosaminidase - NAG, uromodulin, glutathione S-transferase Pi - pi-GST, aquaporin-2), transthoracic echo, clinical and biochemical parameters were evaluated on the 1st and 4th day of hospital stay. Results are presented as mean ±standard deviation or median (interquartile range). Results 40 patients were included in the study with median age 84 (72,8; 86) years, median left ventricle ejection fraction (EF) 35.3 (26,5; 49) %, median NT-proBNP 8967.5 (3024; 15241) pg/ml. LDR was found in 14 (35%) patients. Univariate analysis identified the following risk factors for LDR: urine pi-GST concentration on admission and on the 4th day, right ventricle to pulmonary circulation coupling index (TAPSE/PASP ratio), presence of mitral regurgitation, serum creatine concentration, serum urea concentration, serum LDL concentration. Logistic regression analysis identified pi-GST concentration as a significant independent risk factor for LDR in this population: odds ratio (OR) 5.75 [95% confidence interval (CI) 1.271–25.990]. Conclusions Urine pi-GST on admission and after 4 days of treatment might be a marker for a development of LDR in patients with congestive HF exacerbation.

Impaired striatal glutathione-ascorbate metabolism induces transient dopamine increase and motor dysfunction.

Identifying initial triggering events in neurodegenerative disorders is critical to developing preventive therapies. In Huntington's disease (HD), hyperdopaminergia-probably triggered by the dysfunction of the most affected neurons, indirect pathway spiny projection neurons (iSPNs)-is believed to induce hyperkinesia, an early stage HD symptom. However, how this change arises and contributes to HD pathogenesis is unclear. Here, we demonstrate that genetic disruption of iSPNs function by Ntrk2/Trkb deletion in mice results in increased striatal dopamine and midbrain dopaminergic neurons, preceding hyperkinetic dysfunction. Transcriptomic analysis of iSPNs at the pre-symptomatic stage showed de-regulation of metabolic pathways, including upregulation of Gsto2, encoding glutathione S-transferase omega-2 (GSTO2). Selectively reducing Gsto2 in iSPNs in vivo effectively prevented dopaminergic dysfunction and halted the onset and progression of hyperkinetic symptoms. This study uncovers a functional link between altered iSPN BDNF-TrkB signalling, glutathione-ascorbate metabolism and hyperdopaminergic state, underscoring the vital role of GSTO2 in maintaining dopamine balance.

Oxidative Stress Associated With Increased Reactive Nitrogen Species Generation in the Liver and Kidney Caused by a Major Metabolite Accumulating in Tyrosinemia Type 1.

Tyrosinemia type 1 (TT1) is caused by fumarylacetoacetate hydrolase activity deficiency, resulting in tissue accumulation of upstream metabolites, including succinylacetone (SA), the pathognomonic compound of this disease. Since the pathogenesis of liver and kidney damage observed in the TT1-affected patients is practically unknown, this study assessed the effects of SA on important biomarkers of redox homeostasis in the liver and kidney of adolescent rats, as well as in hepatic (HepG2) and renal (HEK-293) cultured cells. SA significantly increased nitrate and nitrite levels and decreased the concentrations of reduced glutathione (GSH) in the liver and kidney, indicating induction of reactive nitrogen species (RNS) generation and disruption of antioxidant defenses. Additionally, SA decreased the GSH levels and the activities of glutathione peroxidase, glutathione S-transferase, glutathione reductase, and superoxide dismutase in hepatic and renal cells. Noteworthy, melatonin prevented the SA-induced increase of nitrate and nitrite levels in the liver. Therefore, SA-induced increase of RNS generation and impairment of enzymatic and nonenzymatic antioxidant defenses may contribute to hepatopathy and renal disease in TT1.

Effects of diuron and two of its metabolites in biochemical markers and behavior of zebrafish larvae.

Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is an herbicide used in many crops, including sugar cane cultivation. It is commonly found in aquatic ecosystem and is of high concern due to its ability to persist in the environment. Diuron metabolites include DCA (3,4-dichloroaniline) and DCPMU (3-(3,4-dichlorophenyl-1-methylurea). The objective of this study was to evaluate the effects of diuron and two of its metabolites in zebrafish (Danio rerio) developing embryos, from biochemical to individual level. Activities of the enzymes acetylcholinesterase (AChE), catalase (CAT), glutathione-S-transferase (GST), andlactate dehydrogenase (LDH) and the levels of lipid peroxidation (LPO), swimming activity, and body length were investigated after an exposure of 120h, and the heart rate was determined after 48h of exposure. The range of concentrations tested was 0.003-3.000mg/L diuron, 0.020-1.500mg/L DCA, and 0.020-2.100mg/L DCPMU. Results showed that AChE activity was inhibited by diuron (3.000mg/L) and DCPMU (0.326, 0.828mg/L). However, the swimming activity of fish larvae exposed to diuron or its metabolites was not affected. The CAT was induced by DCPMU, and GST was induced by diuron. This suggests that CAT is acting to cope with oxidative stress induced by DCPMU and GST might have a role in the detoxification of diuron. In addition, larvae exposed to DCA (0.633 and 1.500mg/L) had a reduction in their length, and larvae exposed to diuron (0.754 and 3.000mg/L) and DCA (0.267, 0.633, and 1.500mg/L) presented bradycardia, suggesting cardiotoxicity. Overall, results indicate that diuron, DCA, or DCPMU induces adverse effects during the early phases of zebrafish development, such as the impairment of neurotransmission and cardiovascular function and alterations in antioxidant enzymes and growth. Diuron appeared as more toxic than its metabolites since the lowest LOEC (0.012mg/L) and higher integrated biomarker response (IBR) values were obtained with exposure to this herbicide. Furthermore, as it is fast degraded into DCA and DCPMU, which also affected the zebrafish developing embryos at environmentally relevant concentrations, its use might be of concern in ecosystems that receive agriculture runoff due to their potential adverse effects to aquatic biota.

ApCarE4 and ApPOD3 participate in the adaptation of pea aphids to different alfalfa varieties

The adaptability of insects to hosts has long been a focal point in the study of insect-plant interactions. The pea aphid (Acythosiphon pisum), a significant pest of numerous leguminous crops, not only inflicts direct economic losses but also disseminates various plant viruses. To understand how pea aphids adapt to diverse alfalfa varieties. We analyzed the differentially expressed genes (DEGs) of pea aphids in distinct alfalfa varieties using transcriptome sequencing, and subsequently conducted functional validation of these genes. Comparative analysis between pea aphids feeding on susceptible and resistant strains revealed that DEGs in aphids feeding on resistant strains were primarily associated with transcriptional enrichment in the sugar, amino acid, protein, and lipid metabolism pathways. Fourteen DEGs related to adaptation of the pea aphid to alfalfa were chosen, including five carboxylesterases (CarE), four cytochrome P450s, three glutathione S-transferases, and two peroxidases (POD). RT-qPCR results indicated significant up-regulation of two carboxylesterase genes and two peroxidase genes after 24 h of feeding resistant alfalfa (Gannong 5, GN5) compared to the susceptible varieties (Hunter River, LRH), particularly highlighting the high expression levels of ApCarE4 and ApPOD3. Simultaneously, RNAi-induced knockdown of ApCarE4 and ApPOD3 led to a higher mortality of pea aphids in the alfalfa Hunter River. These results indicate that ApPOD3 and ApCarE4 are involved in the detoxification of metabolic functions in the adaptation of pea aphids to host switching. These findings contribute to the understanding of pea aphid adaptation to host plants and lay a foundation for further exploration of the physiological roles of carboxylesterase and peroxidase genes in pea aphids.

Biomarker and adverse outcome pathway responses of Tubifex tubifex(sludge worm) exposed to environmentally-relevant levels of acenaphthene: insights from behavioral, physiological, and chemical structure-activity analyses.

Polycyclic aromatic hydrocarbons (PAHs), including acenaphthene, pose a significant threat to aquatic ecosystems by harming vital organisms such as benthic invertebrates. This study evaluated the impact of environmentally relevant concentrations of acenaphthene on Tubifex tubifex, focusing on sublethal acute toxicity and subchronic biomarker responses. Key biomarkers assessed included histopathological changes and the modulation of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), and malondialdehyde (MDA). Additionally, the study examined structure-activity relationships and species sensitivity distribution (SSD). Concentrations exceeding the solubility threshold of acenaphthene (3.9 mg/L) triggered distinct, concentration-dependent behavioral responses in Tubifex tubifex, such as clumping, mucus secretion, and body wrinkling. Prolonged exposure exacerbated these behavioral dysfunctions, while subchronic exposure resulted in significant histopathological alterations, including epithelial hyperplasia, inflammation, edema, fibrosis, and degenerative changes. The edematic appearance of the body wall suggested a potential immune response to exposure. Furthermore, increased activities of CAT, SOD, and GST indicated oxidative stress in the worms. The study found a 1.5-fold increase in CAT and GST activity, a fivefold increase in SOD, and a striking 100-fold increase in MDA levels compared to controls, signifying an overwhelmed antioxidant defense system and potential cellular disruption. The SSD curve revealed hazard concentrations (HC50 and HC90), indicating that Tubifex tubifex exhibited lower sensitivity to acenaphthene compared to other taxa. In silico analysis and read-across models confirmed the potential of acenaphthene to induce significant oxidative stress upon exposure. The correlation between biomarker responses and structure-activity relationship analysis highlighted the aromatic nature of acenaphthene as a key factor in generating reactive metabolites, inhibiting antioxidant enzymes, and promoting redox cycling, ultimately contributing to adverse outcomes. These findings, coupled with behavioral responses and SSD curve inferences, underscore the importance of the solubility threshold of acenaphthene as a critical benchmark for evaluating its ecological impact in aquatic environments.

Decitabine Enhances Sorafenib Sensitivity in Renal Cell Carcinoma by Promoting BIN1 and SYNE1 Expressions.

Renal cell carcinoma (RCC), especially clear cell RCC (ccRCC), significantly impacts health, and results in particularly poor outcomes in patients at the advanced stage. Resistance to vascular endothelial growth factor (VEGF) pathway-targeting tyrosine kinase inhibitors (TKIs) is a major barrier in effective ccRCC treatment. Herein, we aim to explore how decitabine mediates bridging integrator 1 (BIN1) and spectrin repeat containing nuclear envelope protein 1 (SYNE1) to impact resistance of ccRCC to sorafenib. Employing bioinformatics on datasets GSE64052 and CancerSea, we identified genes linked to TKI resistance, ultimately focusing on SYNE1. We assessed influences of SYNE1 overexpression and BIN1 knockdown via quantitative real-time PCR (qRT-PCR) and Western blot. Assessment of cell viability and apoptosis was accomplished using cell counting kit-8 (CCK-8) assays and flow cytometry. The investigation into the potential interactions between SYNE1 and BIN1, as well as their impacts on sorafenib sensitivity was accomplished by Co-Immunoprecipitation (Co-IP) and Glutathione-S-transferase (GST) Pull-down. SYNE1 was substantially down-regulated in sorafenib-resistant ccRCC cells, and its overexpression increased sorafenib sensitivity, decreased viability and enhanced apoptosis. Interaction between BIN1 and SYNE1 was confirmed, with BIN1 level lower in resistant cells. BIN1 knockdown reduced the beneficial effects of SYNE1 overexpression on sorafenib sensitivity. Decitabine treatment elevated both SYNE1 and BIN1, while boosting apoptosis and reducing sorafenib resistance. SYNE1 contributes to the modulation of sorafenib resistance in ccRCC cells through interacting with BIN1. Decitabine treatment enhances expressions of these two proteins to improve TKI response, suggesting a potential strategy for counteracting resistance and bettering patient outcomes.

Neurotoxicity, Cytotoxicity, and Genotoxicity of Phyto-radio Synthesized Selenium Nanoparticles in Culex pipiens Complex.

Effective mosquito management strategies are crucial to minimize the number of mosquito-borne diseases. Selenium nanoparticles (SeNPs) are promising in mosquito control because they are effective and eco-friendly rather than synthetic insecticides. The current study was conducted to evaluate the impact of SeNPs on the detoxification enzymes, acetylcholine esterase (AChE), glutathione S-transferase (GST), and α-carboxyl esterase (α-CarE), in larval instars of Culex pipiens complex at the LC50 concentration. In 3rd instar larvae treated with microwave-assisted selenium nanoparticles (SeNPs-MW) and gamma-assisted selenium nanoparticles (SeNPs-G), it was found that AChE activity was significantly inhibited. On the other hand, significant increases in GST and α-CarE activities were observed. Additionally, genotoxic and ultrastructure studies of midgut epithelial cells in 3rd instar larvae revealed DNA damage and cell lysis, including destruction of the cell membrane, microvilli, and nuclei. These findings suggest that SeNPs have an adverse effect on AChE gene expression, resulting in its downregulation. This downregulation can be attributed to the formation of reactive oxygen species induced by SeNPs that can modulate the host defense mechanism leading to apoptosis and subsequent larval mortality. The present study was the first to use phyto-microwave-assisted and gamma-assisted synthesis of SeNPs which provides an eco-friendly and cost-effective solution to reduce the risk of chemical insecticides. Furthermore, an integrated pest management program (IPM) using nanocides can be successfully developed for mosquito control.

Molecular and Cellular Characterization of the Glutathione Transferases Involved in the Olfactory Metabolism of the Mammary Pheromone.

Odorant metabolizing enzymes, considered as critical olfactory perireceptor actors, control the odor molecules reaching the olfactory epithelium by biotransforming them. As an odorant, the mammary pheromone, i.e., 2-methylbut-2-enal (2MB2), emitted in the milk of lactating female rabbits triggers typical nipple searching-grasping behavior through orocephalic movements in newborn rabbits but not in weaned rabbits. We previously showed that 2MB2 perception is significantly modified when its glutathione transferase-dependent olfactory metabolism is affected in newborns. Here, enzymatic assays of the recombinant enzymes GSTA1, M1, and P1 revealed the activity of these enzymes toward the mammary pheromone. Histological experiments revealed strong expression of the GSTA class restricted to the Bowman glands and of GSTP1 in the nuclei of sustentacular cells. Moreover, some modulations of GSTs have been demonstrated, including a significant increase in GSTP1 expression (2-fold in mRNA, p value < 0.001; protein, p value: 0.031) after 45 min of mammary pheromone exposure at 10-2 g/mL and an increase in GSTA expression in weaned rabbits compared with newborn rabbits (3-fold in mRNA, p value: 0.011; protein, p value: 0.001). Our results provide new insights into the activity, cellular expression, and modulation of the mammary pheromone GST-metabolizing enzymes and clues about their olfactory function.

Metabolic dysfunction-associated steatotic liver disease-induced changes in the antioxidant system: a review.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogeneous condition characterized by liver steatosis, inflammation, consequent fibrosis, and cirrhosis. Chronic impairment of lipid metabolism is closely related to oxidative stress, leading to cellular lipotoxicity, mitochondrial dysfunction, and endoplasmic reticulum stress. The detrimental effect of oxidative stress is usually accompanied by changes in antioxidant defense mechanisms, with the alterations in antioxidant enzymes expression/activities during MASLD development and progression reported in many clinical and experimental studies. This review will provide a comprehensive overview of the present research on MASLD-induced changes in the catalytic activity and expression of the main antioxidant enzymes (superoxide dismutases, catalase, glutathione peroxidases, glutathione S-transferases, glutathione reductase, NAD(P)H:quinone oxidoreductase) and in the level of non-enzymatic antioxidant glutathione. Furthermore, an overview of the therapeutic effects of vitamin E on antioxidant enzymes during the progression of MASLD will be presented. Generally, at the beginning of MASLD development, the expression/activity of antioxidant enzymes usually increases to protect organisms against the increased production of reactive oxygen species. However, in advanced stage of MASLD, the expression/activity of several antioxidants generally decreases due to damage to hepatic and extrahepatic cells, which further exacerbates the damage. Although the results obtained in patients, in various experimental animal or cell models have been inconsistent, taken together the importance of antioxidant enzymes in MASLD development and progression has been clearly shown.

Effects of freshness of poultry by-product meal on the growth performance, immune response, and hepatopancreatic health of Macrobrachium rosenbergii

A 73-day feeding trial was conducted to determine the effects of the freshness of poultry by-product meal on the growth performance, immune response and hepatopancreatic health of giant freshwater prawn, Macrobrachium rosenbergii. Three semi-purified diets were formulated containing 2.5 % poultry by-product meal with different TVB-N value, designated as L group (untreated poultry by-product meal, TVB-N 10 mg/100 g, i.e., dietary TVB-N 55 mg/100 g), M group (TVB-N 300 mg/100 g, i.e., dietary TVB-N 60 mg/100 g), and H group (TVB-N 450 mg/100 g, i.e., dietary TVB-N 68 mg/100 g), and fed to three groups of prawns (initial weight: 0.82 ± 0.01 g), respectively. Results showed that the weight gain rate (WGR) and specific growth rate (SGR) of prawns significantly decreased with the TVB-N value increased (P < 0.05). The survival rate (SR) and hepatosomatic index (HSI) of prawns in group M and group H were significantly decreased (P < 0.05), while the feed conversion ratio (FCR) was significantly increased (P < 0.05). In addition, the lipase (LPS) and α-amylase (α-AMS) activity of prawns in group L was significantly higher than that in group H (P < 0.05). With the poultry by-product meal TVB-N value increased, the activity of total superoxide dismutase (T-SOD) and glutathione S-transferase (GST) was significantly decreased. RT-qPCR results showed that the expression of bok in group H was significantly higher than that in group L and group M (P < 0.05), the expressions of caspase3, caspase9, bax, and nf-κb in group H were significantly higher than that in group L (P < 0.05). High temperature stress and ammonia nitrogen stress significantly decreased the cumulative survival rate of prawns in group M and group H. Conclusively, it is necessary to guarantee the freshness of the ingredients in prawn formulated diets, and the TVB-N value of diets is recommended not to exceed 60 mg/100 g.

Effect of donor GSTM3 rs7483 genetic variant on tacrolimus elimination in the early period after liver transplantation.

Glutathione S-transferase mu (GSTM) belongs to the group of phase II drug-metabolizing enzymes, and the GSTM1 genetic variant has been reported to have a potential association with the metabolism of immunosuppressive drug after renal transplantation. The effect of donor and recipient GSTMs genetic variants on tacrolimus (Tac) metabolism was the focus of our investigation in this study. A total of 203 liver transplant patients were recruited for the study. In the training set (n=110), twenty-one SNPs in five genes (GSTM1-5) were genotyped by the drug-metabolizing enzymes and transporter (DMET) microarray. CYP3A5 rs776746 and GSTM3 rs7483 were genotyped using a Mass ARRAY platform in the validating set (n=93). Tac C/D ratios of donor GSTM3 rs7483 AA carriers were significantly lower than those with the G allele at weeks 1, 2, 3 and 4 after liver transplantation (LT). Multivariate analysis was conducted on the training set and validating set, donor and recipient CYP3A5 rs776746, donor GSTM3 rs7483 and total bilirubin were identified as independent predictors of Tac C/D ratios in the early period after LT. Combining CYP3A5 rs776746 and donor GSTM3 rs7483 genotypes, Tac C/D ratios were observed to be increasingly lower with increasing numbers of alleles associated with fast metabolism. Moreover, the risk of a supratherapeutic C0 (Tac > 15 ug/L) was significantly higher for poor metabolizers than the other groups at week 1 after LT. There was a significant association between the donor GSTM3 rs7483 genetic variant and Tac metabolism in the early period after LT. Genotype classification might have a better predictive ability of the initial Tac doses.

Hematobiochemical Changes, Immunological Response and Immune Gene Expression in Nile Tilapia (Oreochrom niloticus) Experimentally Infected with Shewanella putrefaciens

Background: In this work, hematobiochemical changes, immunological responses, and histopathological changes in Nile tilapia (Oreochromis niloticus) experimentally infected with Shewanella putrefaciens were studied. Methods: O. niloticus was experimentally infected with S. putrefaciens (4SK/SRLFDA/19) at a concentration of 1.508×106CFU/ml per fish. Gross symptoms, namely hemorrhage on the body surface, skin discoloration, slow or nervous behavior, shallow necrotizing ulcers on the skin, fin erosions and abdominal distension were observed 5 to 6 days after infection. Fish were anesthetized and blood samples were collected at 0, 2, 4, 7, 10, 14, 20 and 27 days after the experimental infection to assess the hematobiochemical and immunological responses. For haematobiochemical responses, tests that included hemoglobin (Hb), leukocyte count (Lc), erythrocyte, hematocrite (Ht), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), cholesterol (CHO), glucose (GLU) and triglyceride were assessed. Result: Values of hematocrit, hemoglobin, albumin, globulin, erythrocyte, MCHC, cholesterol and triglyceride were significantly (p less than 0.05) decreased. Lc, MCV, MCH, and glucose values were significantly (p less than 0.05) increased. Respiratory burst activity (RBA) and serum total protein values were significantly (p less than 0.05) decreased. Relative expression of immune gene toll like receptor 4 (TLR4), stress genes heat shock proteins 70, 90 (HSP70, HSP90), oxidative stress gene glutathione S-transferases (GST) and inflammatory gene interleukin 6 (IL6) was significantly higher in experimentally infected fishes compared to control.

Glutathione and Selenium Supplementation Attenuates Liver Injury in Diethylnitrosamine-Induced Hepatocarcinogenic Mice by Enhancing Glutathione-Related Antioxidant Capacities

Excess oxidative stress and inadequate antioxidant capacities are critical features in the development of hepatocellular carcinoma. This study aimed to determine whether supplementation with glutathione (GSH) and/or selenium (Se), as antioxidants, attenuates diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. C57BL/6J male mice were randomly assigned to control, DEN, DEN + GSH, DEN + Se, and DEN + GSH + Se groups for 20 weeks. Daily supplementation with GSH and/or Se commenced in the first experimental week and continued throughout the study. DEN was administered in weeks 2–9 and 16–19 of the experimental period. DEN administration induced significant pathological alterations of hepatic foci, evidenced by elevated levels of liver function, accompanied by high malondialdehyde (MDA) levels; low GSH levels; and glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) activities. Supplementation with GSH and Se significantly ameliorated liver pathological changes, reducing liver function and MDA levels while increasing GSH levels and GPx, GR, and GST activities. Notably, combined supplementation with GSH and Se more effectively increased the GSH/glutathione disulfide ratio and GPx activity than individual supplementation. Supplementation with GSH and Se attenuated liver injury in DEN-induced hepatocarcinogenic mice by enhancing GSH and its related antioxidant capacities, thereby mitigating oxidative damage.

Differential Hepatic Expression of miRNA in Response to Aflatoxin B1 Challenge in Domestic and Wild Turkeys

Aflatoxin B1 (AFB1) is a major foodborne mycotoxin that poses a significant economic risk to poultry due to a greater degree of susceptibility compared to other agricultural species. Domesticated turkeys (Meleagris gallopavo) are especially sensitive to AFB1; however, wild turkeys (M. g. silvestris) are more resistant. A lack of functional isoforms of hepatic glutathione S-transferases (GSTs), an enzyme that plays a role in the detoxification of aflatoxin, is suspected as the reason for the increased sensitivity. Previous studies comparing the gene expression of domesticated and wild turkeys exposed to AFB1 identified hepatic genes responding differentially to AFB1, but could not fully explain the difference in response. The current study examined differences in the expression of microRNAs (miRNAs) in the livers of wild and domesticated turkeys fed dietary AFB1 (320 μg/kg in feed). Short-read RNA sequencing and expression analysis examined both domesticated and wild turkeys exposed to AFB1 compared to controls. A total of 25 miRNAs was identified as being significantly differentially expressed (DEM) in pairwise comparisons. The majority of these have mammalian orthologs with known dysregulation in liver disease. The largest number of DEMs occurred between controls, suggesting an underlying difference in liver potential. Sequences of the DEMs were used to identify potential miRNA binding sites in target genes, resulting in an average of 4302 predicted target sites per DEM. These DEMs and gene targets provide hypotheses for future investigations into the role of miRNAs in AFB1 resistance.

The moderation effect of GSTM1/GSTT1 gene polymorphisms on the association of sperm mitochondrial DNA copy number and sperm mobility

Oxidative stress (OS) is believed to be a significant factor in the decline of semen quality, with mitochondrial DNA copy number (mtDNAcn) serving as a sensitive biomarker for both semen quality and mitochondrial dysfunction resulting from oxidative stress. While glutathione S-transferases (GSTs) are commonly known as ‘antioxidant’ enzymes, there is ongoing debate regarding the relationship between GST genotypes and semen quality. In a study involving 568 male volunteers from the outpatient department of Puyang Reproductive Medicine Center, sperm mtDNAcn, semen quality, and GSTM1/GSTT1 genotypes were analyzed to investigate the potential link between GSTM1/GSTT1 gene variations and semen quality, as well as the impact of GSTs gene variations on the connection between sperm mtDNAcn and semen quality. Adjusting for variables such as age, BMI, smoking, and alcohol consumption, it was found that mtDNAcn was significantly correlated with decreased sperm concentration and total sperm count (b = − 0.109, − 0.128, respectively; P = 0.002, 0.001, respectively). GSTM1 was associated with progressive motility (OR 0.390, 95% CI 0.218, 0.697), Straight line velocity (VSL) (OR = 0.606, 95% CI 0.385, 0.953), and Straightness (STR) (OR 0.604, 95% CI 0.367, 0.994), while GSTT1 was linked to progressive motility (OR 0.554, 95% CI 0.324, 0.944) and Beat crossover frequency (OR 0.624, 95% CI 0.397, 0.982). The GSTT1 was found to moderate the relationship between mtDNAcn and sperm motility parameters linearity (LIN), STR, and Wobble (WOB), with additive interaction effects observed between GSTT1 and mtDNAcn on LIN, STR, and WOB (P for interaction = 0.008, 0.034, 0.010, respectively). Overall, this study suggests that GSTT1 and GSTM1 gene variations may play a role in sperm motility, with GSTT1 potentially influencing the impact of oxidative stress on sperm motility.

A multiple biomarker approach to understand the effects of microplastics on the health status of European seabass farmed in earthen ponds on the NE Atlantic coast

The occurrence of microplastics (MPs) in aquaculture environments is a growing concern due to their potential negative effects on fish health and, ultimately, on seafood safety. Earthen pond aquaculture, a prevalent aquaculture system worldwide, is typically located in coastal and estuarine areas thus vulnerable to MP contamination. The present study investigated the possible relation between MP levels of European seabass (Dicentrarchus labrax) farmed in an earthen pond and its health status. More precisely, two groups of fish were established based on the lowest and highest number of MPs found collectively in their gastrointestinal tract (GIT), liver, and dorsal muscle: fish with ≤2 MP/g and fish with ≥4 MP/g. The intestinal integrity and oxidative stress biomarkers in the liver and dorsal muscle were evaluated in the established groups. No significant differences in the biometric and organosomatic parameters between groups were observed. The results indicated a significant increase in the number of acid goblet cells (GC) in the rectum of fish with higher MP levels (p = 0.016). Increased acid GC number may constitute a first defence strategy against foreign particles to protect the intestinal epithelium. No significant differences in oxidative stress biomarkers between the two fish groups were observed, namely in the activity of superoxide dismutase, catalase, glutathione reductase, and glutathione S-transferase in the liver, or in lipid peroxidation levels in the liver and dorsal muscle. The overall results suggest that MP levels were possibly related to an intestinal response but its potential implications on the health status of pond-farmed seabass warrant further investigation. Monitoring MP occurrence across stages of aquaculture production could help to elucidate the potential threats of MPs to fish health.

Phytochemical screening and toxicity assessment of compounds isolated from the leaves of Mangifera indica L. for the control of Spodoptera litura (Lepidoptera; Noctuidae)

This study aimed to analyze the phytochemical composition and antioxidative capabilities of mango leaves (Mangifera indica L., Nam Dok Mai), indigenous to Sa Kaeo Province, Thailand. Various solvents with differing polarities, including n-hexane, DCM, ethyl acetate, and MeOH, were utilized for leaf extraction. The findings revealed the existence of eight groups of phytochemical compounds: alkaloids, flavonoids, coumarins, saponins, tannins, terpenoids, steroids, and cardiac glycosides. The MeOH crude extract exhibited the highest concentration of total phenolic compounds at 409.88 ±0.02 mg GAE/g. Furthermore, the MeOH crude extract demonstrated the strongest antioxidant activity, with an IC50 value of 0.52 ±0.02 μg/ml, as determined by the DPPH method. High-performance liquid chromatography (HPLC) was employed to identify gallic acid and mangiferin in the MeOH crude extract. Laboratory tests were conducted using the topical application method to evaluate the toxicity of the M. indica leaf crude extract on 2nd instar Spodoptera litura larvae. The MeOH crude extract exhibited high efficacy, with an LD50 value of 10.58 µg per larvae within 24 hours. Gallic acid and mangiferin were identified as the primary active ingredients, with LCD50 values of 1.19 µg per larvae and 1.90 µg per larvae, respectively, within 24 hours. Additionally, the impact on detoxification enzymes (24 hours post-treatment) was assessed in surviving 2nd instar S. litura larvae using the topical application method. The MeOH extract treatment resulted in 1.31-fold inhibition of carboxylesterase (CE), 1.31-fold inhibition of glutathione-S-transferase (GST), and 1.32-fold inhibition of acetylcholinesterase (AChE).

Elevated temperature increases the susceptibility of D. magna to environmental mixtures of carbamazepine, tramadol and citalopram

The joint risks assessment of thermal stress and rising loads of pharmaceuticals (PhACs) in surface waters is a relevant topic in aquatic ecotoxicology. This study investigated the relevance of increased water temperature to alter the acute toxicity of environmentally relevant carbamazepine (CBZ), citalopram (CIT) and tramadol (TRA) concentrations as mixtures (ECs) and delayed outcomes in Daphnia magna. Responses of detoxification and antioxidant pathways in premature daphnids post an acute 24 h (pulsed) exposure to the PhACs mixtures and delayed responses as the reproductive output over 14 days recovery were investigated under 21- and 26 °C incubation. Biphasic modulation in glutathione S-transferase (GST) activity and significant inhibition of superoxide dismutase (SOD) activity were observed in both thermal regimes with significant shift in effective thresholds from 10-fold ECs at 21 °C to ECs at 26 °C incubation. Significant induction in catalase (CAT) activity and oxidative stress development were recorded at elevated temperatures from the 10-fold ECs dose onward. Pulsed exposures at 26 °C also led to significant decrease in the reproduction of daphnids above the 10-fold ECs of PhACs. The Integrated Biomarker Response scoring (IBRv2) approach outlined a 1.8-fold increase in alterations of daphnids exposed to 100-fold ECs of PhACs at 26 °C.