Elevation Of Glutathione S-transferase Activity Research Articles

Assessing the molluscicidal and biochemical activities of New-Fort®, an inorganic fertilizer against Theba pisana snails

Terrestrial snails are a significant issue in agricultural production worldwide. The use of nitrogen - phosphorus - potassium (NPK) based fertilizers played an important role in meeting the food demand throughout the world, so its effectiveness against land snails needs to be investigated. This study was conducted to evaluate toxic lethal effect of New-Fort®, an inorganic NPK based fertilizer, in the field for 3, 7 and 10 days and in the laboratory for 24, 48 and 72 h against Theba pisana snails. Also, the impact of its sub-lethal doses (1/10, 1/5, 1/4 and 1/2 of 48 h-LD50) on biochemical parameters were determined under laboratory conditions. The results showed that the snails percent reduction in the field were 21.4, 61.0 and 80.0 % after 10 days' application of quarter, half and one field rate and the values of LD50 in the laboratory were 4.94, 4.56 and 4.24 mg/g b.w at 24, 48 and 72 h, respectively. New-Fort® sub-lethal doses caused a significant inhibition in catalase, γ-glutamyl transferase and acetylcholinesterase activities. It also elicited a significant elevation in glutathione S-transferase activity post exposure to 1/10 and 1/5 of LD50, whereas an opposite effect was occurred after exposure to 1/4 and 1/2 of LD50. Lipid peroxidation level was reduced in snails treated with 1/10 and 1/5 of LD50, whereas it increased in 1/4 and 1/2 of LD50- treated snails. Moreover, a significant inhibition in alkaline phosphatase activity at all tested doses, with the exception of 1/2 of LD50 was observed. An increase in alanine aminotransferase and aspartate aminotransferase activities were occurred after all tested doses exposure. Our findings highlighted on how biochemical changes can be exploited to better understand the mechanisms underlying New-Fort® fertilizer toxicity against the land snail, T. pisana, as well as how to benefit from NPK fertilizers application in snail control.

Lupeol Stearate Accelerates Healing and Prevents Recurrence of Gastric Ulcer in Rodents.

Objective The focus of this study was to evaluate the gastric healing effect of lupeol stearate (LS) and its ability to minimize ulcer recurrence in rodents. Methods To evaluate the gastric healing properties of LS, rats were subjected to 80% acetic acid-induced ulcer model and treated with vehicle, LS (1 mg/kg, p.o.), or omeprazole (20 mg/kg, p.o.), twice daily by seven days. The gastric ulcers were evaluated macroscopically, histologically, and biochemically. To evaluate the effects of LS in gastric ulcer recurrence, mice were ulcerated with 10% acetic acid and treated with vehicle, LS (1 mg/kg, p.o.), or ranitidine (100 mg/kg, p.o.), twice a day for ten days. Then, ulcer recurrence in these animals was induced by IL-1β at five days after the treatment period. Results The oral treatment with LS accelerated gastric healing by 63% in rats compared to the vehicle group, evidenced by histological improvement and increased gastric mucin levels. Moreover, the gastric healing effects of LS in rats were accompanied by an elevation in glutathione S-transferase activity and a reduction in myeloperoxidase activity. Furthermore, the LS treatment reduced the recurred lesions in mice. Conclusions The oral treatment of LS accelerates gastric healing in rats by favoring mucus production and reducing neutrophil migration, and it also can reduce ulcer recurrence. These data highlighted this compound as promising for developing new pharmacological strategies for the management of gastric ulcer.

Glutathione S-Transferase Activity of Human Erythrocytes Incubated in Aqueous Solutions of Five Antimalarial Drugs

Levels of human erythrocyte glutathione S-transferase (GST) activity were ascertained in the presence of separate increasing concentrations (0.2, 0.4, 0.6, and 0.8 mg% w/v) of five antimalarial drugs {Pyrimethamine/Sulphadoxine (PS), Halofantrine-HCl (H-HCl), Quinine, Artemether/umefantrine (AL) and Chloroquine Phosphate (CP)} in vitro. Determination of erythrocyte GST activity was carried out by spectrotrophotometric method with the standard substrate (1-chloro-2, 4-dinitrobenzene) and co-substrate (reduced gluthathione) at maximum absorbance (λmax) = 340 nm. Human erythrocyte GST activity ranged between 3.27 ± 0.13 and 3.40 ± 0.05 iu/gHb. The addition of increasing concentrations of four antimalarial drugs to assay mixture engendered decreased levels of GST activity in a concentration dependent manner, which was in the order: CP > AL > Quinine > PS. Specifically, 0.8 mg% CP exhibited the highest capacity to cause decreased GST activity from values of 3.41 ± 0.06 to 2.18 ± 0.09 iu/gHb, representing 33.7% relative inhibition of GST activity. In contrast, concentrations of H-HCl between 0.2 and 0.6 mg% caused elevation of GST activity above the values of the control samples. However, the increased levels of GST activity was not significantly different (p > 0.05) compared with the control samples. The five antimalarial drugs exhibited variable capacities to alter human erythrocyte GST activity, which suggest the capability of these drugs to perturb the redox status of human erythrocytes.

Effects of redox cycling compounds on glutathione content and activity of glutathione-related enzymes in rainbow trout liver

In fish, as in other aerobic organisms, glutathione and glutathione-related enzymes are important components in the defences against oxidative stress. To study if hepatic glutathione levels and/or activities of glutathione-related enzymes can act as indicators of oxidative stress in fish, we injected rainbow trout ( Oncorhynchus mykiss) intraperitoneally with paraquat (PQ), menadione (MD), naphthazarin (DHNQ), or β-naphthoflavone (β-NF), all known to cause a rise in reactive oxygen species (ROS). After 2 and 5 days of exposure, we measured the activities of hepatic glutathione peroxidase (GPox), glutathione S-transferase (GST), γ-glutamylcysteine synthetase (GCS), and glutathione reductase (GR). We also measured total glutathione (tGSH) and oxidised glutathione (GSSG) in the liver of fish treated with PQ and MD. All chemicals caused an increase in GR activity after 5 days, which ranged from 160% in fish treated with β-NF to 1500% in fish treated with PQ. All chemicals except β-NF caused moderate elevation in GST activity; GPox activity was lower in fish treated with DHNQ and MD, while GCS activity increased twofold in the fish treated with DHNQ, without being affected by β-NF, PQ or MD. After 5 days of treatment with PQ or MD, tGSH content was elevated. Our findings demonstrated that of the parameters included in the study, GR activity was the most responsive to treatment with redox cycling compounds, indicating that GR activity is a promising biomarker of such compounds and possibly indicating oxidative stress in rainbow trout.

Cypermethrin induces glutathione S-transferase activity in the shore crab, Carcinus maenas

Cypermethrin is a synthetic pyrethroid that is particularly toxic to crustacea. It is therefore applied as a chemotherapeutant in the salmonid aquaculture industry for the treatment of sea lice infestations. After use, cypermethrin is released directly into the marine environment, to be diluted by fresh seawater. The shore crab, Carcinus maenas is found in the vicinity of fish farms, and may come into contact with released cypermethrin. The detoxification enzyme, glutathione S-transferase (GST) has been implicated in cypermethrin metabolism in terrestrial arthropods, but this has not yet been demonstrated in crustacea. In this paper we investigate the response of GST activity in Carcinus to cypermethrin exposure, and also the time course of the induction process. GST activity is significantly increased in Carcinus exposed to nominal concentrations of 50 and 500 ng/l of water-borne cypermethrin. Carcinus demonstrate a significant elevation in GST activity following intra-cephalothoracic injection with 10 ng of cypermethrin. GST activity returns to basal levels after 36 h. The potential application of GST activity in Carcinus as a biomarker of cypermethrin exposure is discussed.

Dissolved Humic Substances Can Directly Affect Freshwater Organisms

Direct effects of pure humic substance (BS1 FA) on three different aquatic organisms (Ceratophyllum demersum, Dreissena polymorpha, and Chaetogammarus ischnus) were demonstrated in this study. Exposure to environmentally relevant concentrations (0.5 mg/L) of this humic substance led to the activation of the microsomal and soluble glutathione S-transferase (GST) in Ceratophyllum demersum. Exposure to 3-chlorobiphenyl showed also an elevation of GST activity, which is due to the proposed detoxication metabolism of these chlorinated biphenyl. Coexposure to a mixture of 3-chlorobiphenyl and BS1 FA showed a reduction of enzyme elevation, but still significant over an untreated control. The direct impact of humic substances seems not to be restricted to a specific class of organisms.

The molecular basis of two contrasting metabolic mechanisms of insecticide resistance

The esterase-based insecticide resistance mechanisms characterised to date predominantly involve elevation of activity through gene amplification allowing increased levels of insecticide sequestration, or point mutations within the esterase structural genes which change their substrate specificity. The amplified esterases are subject to various types of gene regulation in different insect species. In contrast, elevation of glutathione S-transferase activity involves upregulation of multiple enzymes belonging to one or more glutathione S-transferase classes or more rarely upregulation of a single enzyme. There is no evidence of insecticide resistance associated with gene amplification in this enzyme class. The biochemical and molecular basis of these two metabolically-based insecticide resistance mechanisms is reviewed.

Time course effects of vanadium supplement on cytosolic reduced glutathione level and glutathione S-transferase activity.

The influence of vanadium, an important dietary micronutrient, was evaluated on the cytosolic reduced glutathione (GSH) content and glutathione S-transferase (GST) activity in several rat target tissues. Supplementation of drinking water with vanadium at the level of 0.2 or 0.5 ppm for 4, 8, or 12 wk was found to increase the GSH level with a concomitant elevation in GST activity in the liver followed by small intestine mucosa, large intestine mucosa, and kidney. The results were almost dose-dependent and mostly pronounced with 0.5 ppm vanadium after 12 wk of its continuous supplementation. Neither the GSH level nor GST activity was significantly altered in forestomach and lung following vanadium supplementation throughout the study. The levels of vanadium that were found to increase the content of GSH and activity of GST in the liver, intestine, and kidney did not exert any toxic manifestation as evidenced from water and food consumption as well as the growth responses of the experimental animals. Moreover, these doses of vanadium did not impair either hepatic or renal functions as they did not alter the serum activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), sorbitol dehydrogenase (SDH), as well as serum urea and creatinine level. All these results clearly indicate that vanadium under the doses employed in our study has a significant inducing role on GSH content with a concurrent elevation in GST activity in the liver and specific extrahepatic tissues without any apparent sign of cytotoxicity. This attribute of vanadium may have a greater importance in terms of biotransformation and detoxification of xenobiotics, including carcinogens. In addition, since the ability to afford an increment in the endogenous GSH-GST pool by anticarcinogenic natural substances has been found to correlate with their activity to inhibit neoplastic transformation, the trace element vanadium may be considered as a novel anticancer agent.

Chemopreventive Action of Ocimum sanctum on 2,12-Dimethylbenz(a)anthracene DMBA-Induced Papillomagenesis in the Skin of Mice

AbstractThe present paper reports the chemopreventive activity of an ethanol leaf extract of Ocimum sanctum on DMBA-induced papillomagenesis in the skin of male Swiss albino mice. A single topical application of DMBA (50 μg/50 μl of acetone) followed, 2 weeks later, by repeated applications of croton oil (1% in acetone, three times/week) resulted in the appearance of skin papillomas in 100% of the animals. However, treatment of the animals with an ethanol leaf extract of Ocimum (800 mg/Kg body weight) through gastric intubation, significantly reduced not only the number of tumor-bearing mice but also the cumulative number of papillomas and the mean number of tumors per mouse. Oral treatment with the Ocimum leaf extract for 15 days resulted in significant elevation of glutathione S-transferase activity in hepatic (P<0.01) and extrahepatic (P<0.01) tissues. Reduced glutathione level was also elevated by treatment with the leaf extract in liver, lung and stomach tissues.

Phosphamidon neurotoxicity

The present study was undertaken to evaluate the neurotoxic effects of the organophosphate, phosphamidon, on glutathione-S-transferase (GST) activity and concentration of sulphhydryl groups, and to study the possible protection against these effects by the simultaneous administration of the antioxidant, acetylhomocysteine thiolactone, commonly known as citiolone. Significant depletion was observed in the GST activity as well as in the level of total and non-protein bound sulphhydryl groups in various CNS regions of phosphamidon-intoxicated rats. When citiolone was administered alone, there was a remarkable elevation in GST activity. However, significant protection against GST inhibition was observed when phosphamidon and citiolone were administered simultaneously.