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Background: Times New Roman 9, single space, contains the brief description of the research. Stroke is the greatest cause of disability and mortality worldwide. Several biological mechanisms underlying this disease such as failure of glutamate reuptake and ATP synthesis, resulting in high levels of reactive oxygen species (ROS), neuroinflammatory responses, and apoptosis, resulted in cell death and brain tissue damage. Neurotherapeutics agents are given to affect the pathophysiological pathways and prevent expanding infarct area. Objective: This study aims to analyze the modulation of Gluthatione S-Transferase (GST) and Tyrosine kinase receptor C (TrkC) by 7,8-DHF as neuroprotective agent in ischemic in silico. Methods: This study used in silico simulation to predict 7,8-dihydroxyflavone (DHF) as neuroprotective agent by using PubChem, RCSB, Biovia Discovery Studio, PyRx, and PyMol. This study analyzes the pharmacodynamics, pharmacokinetics, and molecular interactions between 7,8-DHF as a ligand with GST (13GS) and TrkC (6KZC) as protein target, compared to their native ligand. Results: 7,8-DHF may increase intracellular endogenous antioxidants mainly GST and stimulate TrkC to activate further neuron survival signaling. 7,8 DHF has a much lower bond energy (-8.1 Kcal/mol) when it binds to GST compared to the native ligand (-5.9 Kcal/mol). Besides, binding affinity between 7,8-DHF-TrkC was -9 Kcal/mol, while native ligand-TrkC was -10.6 Kcal/mol. This study showed that there were the same amino acid residues between 7,8-DHF-GST and 7,8-DHF-TrkC, compared to their native ligand. Conclusion: As an adaptive response to hypoxia caused by ischemic stroke, these findings are likely to induce protective mechanism through indirectly TrkC activation which regulates neurogenesis and increasing intracellular endogenous antioxidants.

Microplastic (MP) pollution is a potential threat to marine organisms. In vitro toxicity of MPs and other pollutants, such as pharmaceutically active compounds (PhACs) and brominated flame retardants (BFRs), has been understudied. This study aimed to investigate the effects of polystyrene microplastics (PS-MPs) with different particle sizes on two biomarkers: ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST) in tilapia liver homogenates. The study also examined the combined effects of PS-MPs with various environmental contaminants, including three metal ions (Cu2+, Zn2+, Pb2+), three BFRs, and six PhACs. PS-MPs alone had no remarkable effects on the two biomarkers at the selected concentrations. However, PS-MPs combined with other pollutants significantly affected the two biomarkers in most situations. For EROD activity, PS + metal ions (except Zn2+ at 1000 μg/L), PS + BFRs (except decabromodiphenyl oxide (BDE-209)) or PS+ trimethoprim (TMP) significantly inhibited activity values, whereas PS+ 4-acetaminophen (AMP) induced EROD activity. For GST, PS together with most tested pollutants (except PS+ ibuprofen (IBF)) greatly decreased the activities. Accordingly, future research should focus on combined toxicity of mixtures to set more reasonable environmental safety evaluation standards. • PS-MPs alone had no significant effects on EROD or GST. • PS-MPs combined with other pollutants affected EROD and GST in most situations. • EROD and GST seemed to be suitable biomarkers to evaluate the combined effects of PS and other pollutants. [ABSTRACT FROM AUTHOR]

Fascioliasis is a worldwide parasitic disease in human and domestic animals. The causative agents of fascioliasis are Fasciola hepatica and Fasciola gigantica. In the recent years, fasciola resistance to drugs has been reported in the many of publications. Fasciola spp has detoxification system including GST enzyme which may be responsible for its resistance. Therefore , the aim of the study was to assay of GST enzyme activity in fasciola parasites. Fasciola gigantica and Fasciola hepatica helminths were collected from abattoir as a live and cultured in buffer media for 4 h at 37 °C. Excretory-Secretory products were collected and stored in -80◦C. F. gigantica and Fasciola hepatica were homogenized with homogenizing buffer in a glass homogenizer to prepare of somatic extract. Suspension was then centrifuged and supernatant was stored at -80°C. In order to assay the enzyme activity, excretory-secretory and somatic extracts in the form of cocktails (potassium phosphate buffer, reduced glutathione and 1-chloro-2,4-dinitrobenzene substrates) were prepared and their absorbance recorded for 5 minutes at 340 nm. The total and specific GST activity of F. gigantica somatic and ES products were obtained as 2916.00, 272.01 micromole/minute and 1.33, 1.70 micromole/minute/mg protein, respectively. Fasciola hepatica also showed 2705.00, 276.86 micromole/minute and 1.33, 1.52 micromole/minute/mg protein, respectively. These results are important for analysis of parasite survival / resistance to drugs which use for treatment of fascioliasis.

The resistance mechanisms to oxydemeton-methyl were surveyed in two Iranian strains of the two spotted spider mite, Tetranychus urticae Koch. Bioassay was carried out on two strains, collected from Tehran and Rasht using dipping method. The results of bioassay indicated that resistance ratio was 20.47 for resistant strain. The activity of esterase and glutathione S-transferase in resistant and susceptible strains showed that one of resistance mechanisms to oxydemeton-methyl was esterase-based resistance and glutathione S-transferase. The esterase activity of the resistant strain was 2.5 and 2.14-fold higher than those of the susceptible strain for α-naphtyl acetate (α-NA) and β-naphtyl acetate (β-NA) respectively. The kinetic characteristics acetylcholinesterase (AChE) showed that the AChE of resistant strain had lower affinity to artificial substrates; acetylthiocholine and butyrylthiocholine than that of susceptible strain. I50 of oxydemeton-methyl for resistant and susceptible strains were 2.68×10-6 M and 7.79×10-7 M respectively. The results suggested that AChE of resistant strain is insensitive to oxydemeton-methyl and ratio of AChE insensitivity of resistant to susceptible strain were 3.49 and 7.8-fold to oxydemeton-methyl and paraoxon, respectively.

Fascioliasis is a worldwide parasitic disease in human and domestic animals. The causative agents of fascioliasis are Fasciola hepatica and Fasciola gigantica. In the recent years, fasciola resistance to drugs has been reported in the many of publications. Fasciola spp has detoxification system including GST enzyme which may be responsible for its resistance. Therefore , the aim of the study was to assay of GST enzyme activity in fasciola parasites. Fasciola gigantica and Fasciola hepatica helminths were collected from abattoir as a live and cultured in buffer media for 4 h at 37 °C. Excretory-Secretory products were collected and stored in -80◦C. F. gigantica and Fasciola hepatica were homogenized with homogenizing buffer in a glass homogenizer to prepare of somatic extract. Suspension was then centrifuged and supernatant was stored at -80°C. In order to assay the enzyme activity, excretory-secretory and somatic extracts in the form of cocktails (potassium phosphate buffer, reduced glutathione and 1-chloro-2,4-dinitrobenzene substrates) were prepared and their absorbance recorded for 5 minutes at 340 nm. The total and specific GST activity of F. gigantica somatic and ES products were obtained as 2916.00, 272.01 micromole/minute and 1.33, 1.70 micromole/minute/mg protein, respectively. Fasciola hepatica also showed 2705.00, 276.86 micromole/minute and 1.33, 1.52 micromole/minute/mg protein, respectively. These results are important for analysis of parasite survival / resistance to drugs which use for treatment of fascioliasis.

Excretory-secretory products (ESP) play an important role in the host biochemical defense by means of activities of detoxifying and antioxidant enzymes. The aim of this study was to evaluate praziquantel (PZQ) effects by detection of glutathione S- transferase (GST) and superoxide dismutase (SOD) enzymes activities in ESP samples of Fasciola spp. Fasciola gigantica and Fasciola hepatica adult parasites were collected and cultured within buffer media for 4 h at 37°C. Treated (with 50, 100 and 150 g PZQ) and control ESP samples for each species were collected and centrifuged. The supernatants were stored at -20°C. SOD and GST enzymes activities of ESP samples were estimated photometrically. To determine the statistically-significant difference between ESP of treated and control samples, t-test was conducted. ESP protein bands were detected by gel electrophoresis (SDS-PAGE). SOD enzyme activities level in treated F.hepatica and F. gigantica ESP samples were determined as 0.26, 0.29, 0.76 and 1.73, 1.60, 1.43 U/ml respectively. SOD activities level in control samples were detected 1.31 and 1.35 U/ml. GST activities level in treated F.hepatica and F. gigantica ESP samples were calculated 9.4, 3.1, 23.96 and 435.4, 333.3, 720.9 U/ml. GST activities levels in control samples were detected 43.8 and 134.4 U/ml respectively. Statistical analysis revealed the significant decrease of GST and SOD enzyme activities in treated ESP samples of Fasciola hepatica, and significant increase of GST enzyme activity in treated ESP samples of F. gigantica in comparison to the control samples (p < 0.05). There was also no difference between SDS-PAGE results of treated and control samples. Based on the results of present work, PZQ has decreasing effect on the ESP enzymatic activities of Fasciola hepatica and increasing effect on F. gigantica enzyme activities. In other words, F. hepatica has less capability to protect against xenobiotics and free radicals than F.gigatica does. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether some of the cephalosporin group antibiotics have inhibition effects on GR and GST enzymes with important functions in the metabolic pathway. In this study, some selected cephalosporin group antibiotics on GST and GR enzyme was carried out using 96 rats. 16 groups (16 × 6) were created from these rats, divided to another 4 groups (4 × 24). The resulting groups were named as sham groups, cefazolin groups, cefuroxime groups and cefoperazone groups, respectively. The antibiotics used were injected to cefazolin, cefuroxime and cefoperazone groups. The inhibition effects of the antibiotics were measured in the different time intervals (1st, 3th, 5th, 7th). The statistical investigation of the results was performed using the SPSS software program. Results revealed the complex effects of the tested substances on GR and GST activity at different time intervals and in different tissues (p < 0.05). This indicated that the tested substances could be exposed to different interactions in vivo. The tested antibiotics showed some significant inhibition effects on the GST and GR enzyme activity in some tissues of brain, eye and muscle. The interaction of enzyme - the drug is a key factor to highlight the toxicological mechanism. For this reason, the results obtained from in vivo experiments are crucial to explane the physiological properties of the enzymes. • In this study, some cephalosporins were investigated as in vivo inhibition studies. • The inhibition effects of these compounds were determined against GR, and GST enzymes activities. • These results revealed the complex effects of the tested substances on GR and GST activity at different time intervals and in different tissues. [ABSTRACT FROM AUTHOR]