Nonprotein Sulfhydryl Research Articles

An experimental model of contact dermatitis: Evaluation of the oxidative profile of Wistar rats treated with free and nanoencapsulated clobetasol

ObjectiveAn experimental animal model of contact dermatitis (CD) was used to investigate the effects of free and nanoencapsulated clobetasol propionate on the skin and on the oxidative profile of liver tissue.MethodsFemale Wistar rats were divided into six groups, each containing eight rats. The first group, control (C), was sensitized with solid vaseline. Group 2, (CD), was sensitized with 5% NiSO4. Groups 3 and 4 were sensitized with 5% NiSO4 and treated with free (FC) and nanoencapsulated (NC) clobetasol (0.42 mg/g), respectively, daily for 5 days. Group 5 was treated with nanoencapsulated clobetasol (0.42 mg/g) on days 1, 3, and 5 (C135) and group 6 received a hydrogel containing empty nanoparticles (NP) daily for 5 days. Thiobarbituric acid reactive substances (TBARS), carbonyl levels, non-protein sulfhydryl groups (NPSH) and catalase activity were measured in liver homogenates.ResultsA significant increase was observed in the levels of TBARS, NPSH, and catalase activity for the groups CD and NP.DiscussionOur results suggest that both NiSO4 sensitization and NP administration induced oxidation of cellular lipids and activated the antioxidant enzyme catalase to protect from this damage. These results also indicated that daily treatment with the free and nanoencapsulated clobetasol, as well as treatment with the nanoencapsulated clobetasol every other day, were able to prevent these redox alterations and protect against histological damage.

Protective effect of lutein against benzo(a)pyrene-induced oxidative stress in human erythrocytes

The present study was carried out to evaluate the in vitro antioxidant properties and protective effect of lutein in human erythrocyte against benzo(a)pyrene (B(a)P). It is a well-known environmental carcinogen that produces free radicals under normal metabolic circumstances. B(a)P reacts with cellular macromolecules and produces oxidation of protein, lipid and DNA. Lutein is a carotenoid possessing antioxidant, anticarcinogenic and anti-inflammatory properties. In the present investigation, the protective effect of lutein was assessed in vitro against B(a)P-induced oxidative stress by monitoring antioxidant enzymes, lipid peroxidation (LPO), protein carbonyl content, total sulfhydryl (SH) and nonprotein SH groups and methemoglobin in five groups of erythrocytes that include (i) control group, (ii) vehicle control group, (iii) B(a)P-exposed group, (iv) lutein-exposed group and (v) B(a)P coincubation with lutein group. It was observed that the activities of antioxidant enzymes and SH groups were significantly decreased in B(a)P-treated group when compared with control group. LPO level and protein carbonyl and methemoglobin contents were increased in B(a)P-treated group when compared with control group. The erythrocyte that was coincubated with B(a)P and lutein showed significant increase in the antioxidant enzyme activities and a significant reduction in the level of LPO, methemoglobin and protein carbonyl contents when compared with B(a)P-treated group. The results of the present investigation suggest that lutein possess protective effect against B(a)P-induced oxidative stress, possibly by combating oxidative stress by its free radical scavenging activity.

Effect of Sulfhydryl Modification on Rat Kidney Basolateral Plasma Membrane Transport Function

Transport processes are the hallmark of functioning kidney. Various nephrotoxicants disrupt the transport processes to manifest nephrotoxicity. Of several nephrotoxicants, mercuric chloride (HgCl(2)) depletes the reduced glutathione (GSH) in kidney and has been observed to affect the in vitro p-aminohippurate (PAH) transport by basolateral (BL) membrane vesicles. The role of renal nonprotein sulfhydryls such as, reduced GSH has been demonstrated to affect the PAH transport by BL membrane vesicles. The role of protein sulfhydryls in transport process of PAH by BL membrane is not known. Due to mercury mediated effects on sulfhydryls, the effects of protein-sulfhydryls (-SH) modifying reagents in the current study were investigated on PAH transport by BL membrane. It was observed that modification of -SH by p-chloromercuribenzoate sulphate (pCMBS), and mercuric chloride (HgCl(2)) decreased while recovering the protein -SH with dithiothreitol treatment provided protection against the effects of pCMBS, and HgCl(2) on PAH transport by BL membrane vesicles.

Efflux of glutathione and glutathione complexes from human erythrocytes in response to vanadate

The main objective of the present study was to investigate if vanadate is extruded from the cells in a glutathione dependent manner resulting in the appearance of extracellular glutathione and complexes of glutathione with vanadium. Vanadate significantly depleted intracellular non-protein sulfhydryl (NPSH) levels in a time- and concentration-dependent manner. The intracellular NPSH level was decreased to 0.0 ± 0.0 μmol/ml erythrocyte when exposed to 10 mM of vanadate for 4h. Extracellular NPSH level was increased concomitantly with the intracellular decrease and reached to 0.1410 ± 0.005 μmol/ml erythrocyte in 4h. Intracellular decrease and extracellular increase in NPSH levels were significantly inhibited in the presence of DIDS, a chloride-bicarbonate exchanger which also mediates phosphate and arsenate transport in erythrocytes. In parallel with the increase in extracellular NPSH levels, significant increases in extracellular glutathione levels were detected following exposure to vanadate. Extracellular glutathione levels reached to 0.0150 ± 0.0.001, 0.0330 ± 0.001, and 0.0576 ± 0.002 μmol/ml erythrocyte with 1, 5, and 10 mM of vanadate respectively. Dimercaptosuccinic acid treatment of supernatants significantly increased the glutathione levels measured in the extracellular media. Utilization of MK571 an MRP inhibitor decreased the rate of glutathione efflux from erythrocytes suggesting a role for this membrane transporter in the process. A known methylation inhibitor periodate oxidized adenosine decreased the rate of glutathione efflux from erythrocytes. This observed decrease in extracellular GSH levels suggests that GSH release partly requires a proper cellular methylation process and that part of GSH detected in the extracellular media may arise from GSH-vandium complexes. The results of the present study indicate that human erythrocyte efflux glutathione in reduced free form and in conjugated form/s that can be recovered with dimercaptosuccinic acid when exposed to vanadate.

Edible Oils for Liver Protection: Hepatoprotective Potentiality of Moringa Oleifera Seed Oil against Chemical‐Induced Hepatitis in Rats

In the present study, in vitro antioxidant, antioxidative stress and hepatoprotective activity of Moringa oleifera Lam. seed oil (Ben oil; BO) was evaluated against carbon tetrachloride (CCl(4) ) induced lipid peroxidation and hepatic damage in rats. The oil at 0.2 and 0.4 mL/rat was administered orally for 21 consecutive days. The substantially elevated serum enzymatic (GOT, GPT, ALP, GGT) and bilirubin levels were significantly restored towards normalization by the oil. There was a significant elevation in the level of malondialdehyde (MDA), non-protein sulfhydryl (NP-SH), and total protein (TP) contents in the liver tissue. The results obtained indicated that BO possesses potent hepatoprotective action against CCl(4) -induced hepatic damage by lowering liver marker enzymes, MDA concentration, and elevating NP-SH and TP levels in liver tissue. The biochemical observations were supplemented with histopathological examination of rat liver. The results of this study showed that treatment with Ben oil or silymarin (as a reference) appears to enhance the recovery from hepatic damage induced by CCl(4) . The pentobarbital induced narcolepsy prolongation in mice was retarded by the Ben oil. Acute toxicity test in mice showed no morbidity or mortality. In vitro DPPH radical scavenging and β-carotene-linolic acid assay tests of the BO exhibited a moderate antioxidant activity in both tests used. The possible mechanism(s) of the liver protective activity of Ben oil activity may be due to free radical scavenging potential caused by the presence of antioxidant component(s) in the oil. Consequently, BO can be used as a therapeutic regime in treatment of some hepatic disorders.

Gastroprotective activity of carvacrol on experimentally induced gastric lesions in rodents

The present study aimed to investigate the gastroprotective activity of carvacrol, a monoterpene present in essential oils from several species of medicinal and aromatic plants, by using different models of acute gastric lesions in rodents and also evaluate possible mechanisms involved in this action. For this study, absolute ethanol-, acidified ethanol-, ischemia and reperfusion-, and nonsteroidal anti-inflammatory drug-induced models of gastric lesions in mice and rats were used. The roles of nonprotein sulfhydryl groups, catalase, nitric oxide (NO), ATP-sensitive potassium channels (K(ATP) channels), and prostaglandins in carvacrol-induced gastroprotective effect were investigated. In addition, the effects of carvacrol on gastric secretion and mucus in pylorus-ligated rats were also determined. The results of the present study demonstrated that carvacrol promoted a marked gastroprotection in all models investigated, possibly mediated by endogenous prostaglandins, increase of mucus production, K(ATP) channels opening, NO synthase activation, and antioxidant properties. These findings markedly substantiate further studies to investigate the therapeutic potential of carvacrol as an effective gastroprotective agent and its safety profile in medicinal use.

Tumor Xenograft Response to Redox-Active Therapies Assessed by Magnetic Resonance Imaging Using a Thiol-Bearing DOTA Complex of Gadolinium

Gd-LC6-SH is a thiol-bearing DOTA complex of gadolinium designed to bind plasma albumin at the conserved Cys34 site. The binding of Gd-LC6-SH shows sensitivity to the presence of competing thiols. We hypothesized that Gd-LC6-SH could provide magnetic resonance imaging (MRI) enhancement that is sensitive to tumor redox state and that the prolonged retention of albumin-bound Gd-LC6-SH in vivo can be exploited to identify a saturating dose above which the shortening of MRI longitudinal relaxation time (T1) of tissue is insensitive to the injected gadolinium dose. In the Mia-PaCa-2 pancreatic tumor xenograft model in SCID mice, both the small-molecule Gd-DTPA-BMA and the macromolecule Galbumin MRI contrast agents produced dose-dependent decreases in tumor T1. By contrast, the decreases in tumor T1 provided by Gd-LC6-SH at 0.05 and 0.1 mmol/kg were not significantly different at longer times after injection. SCID mice bearing Mia-PaCa-2 or NCI-N87 tumor xenografts were treated with either the glutathione synthesis inhibitor buthionine sulfoximine or the thiol-oxidizing anticancer drug Imexon, respectively. In both models, there was a significantly greater increase in tumor R1 (=1/T1) 60 minutes after injection of Gd-LC6-SH in drug-treated animals relative to saline-treated controls. In addition, Mercury Orange staining for nonprotein sulfhydryls was significantly decreased by drug treatment relative to controls in both tumor models. In summary, these studies show that thiol-bearing complexes of gadolinium such as Gd-LC6-SH can serve as redox-sensitive MRI contrast agents for detecting differences in tumor redox status and can be used to evaluate the effects of redox-active drugs.

Antinociceptive and anti-ulcerogenic activities of the ethanolic extract of Annona muricata leaf

Ethanolic extract of Annona muricata L., Annonaceae, leaf (AML) was used to investigate its antinociceptive and anti-ulcerogenic activities and the involvement of the mechanism of ethanolic leaves extract of AML in various animal models. Antinociceptive activity of AML extract was done using acetic acid-induced abdominal writhing in mice, formalin test in rats and hot plate test in mice. Furthermore, the anti-ulcerogenic effect of AML extract was studied in ethanol-induced ulcer model in rats, ethanol-induced gastric lesions in L-NAME-pre-treated rats as well as ethanol-induced gastric lesions in NEM-pre-treated rats test model to determine its mechanism. AML exhibited significant and dose-dependent antinociceptive activity. It also significantly decreased the ulcerative lesion produced by ethanol in rats in a dose-dependent manner. Pre-treatment with N-ethymaleimide, a thiol blocker, including mucosal nonprotein sulfhydryl groups, reduced the anti-ulcerogenic effect of AML extract in the same ulcer model, suggesting that AML extract may have active substances such as tannins, flavanoids and triterpenes that increase the mucosal nonprotein sulfhydryl group content.

Protective effect of Chresta martii extract on ethanol-induced gastropathy depends on alpha-2 adrenoceptors pathways but not on nitric oxide, prostaglandins or opioids

Ethnopharmacological relevanceSpecies of Chresta genus- are recognized by the population of northeastern Brazil as traditional herbs used to treat gastric diseases and other disorders. Aim of the studyThis work aimed to find out the action mechanism of Chresta martii hydro alcoholic extract gastro protective effect in the model of ethanol-induced gastropathy. Material and methodsGastropathy was assessed by percentual damaged area determination in photographs of mice opened stomachs. Fasted mice treated with ethanol 99.9% (0.2 ml/animal, p.o.) were pre-treated with Chresta martii hydro alcoholic extract (HAE) (50, 100 or 200 mg/kg, p.o.), ranitidine (80 mg/kg, p.o.) or saline (5 ml/kg; p.o.) in different experimental sets, in which pharmacological tools (naloxone, indomethacin, Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) or yohimbine) were added in order to clarify a possible action mechanism. Animals were sacrificed 30 min after ethanol challenge to stomach analysis. Determination of non-protein sulfhydryl groups and tissue hemoglobin, besides histological assessment (H&E) were taken to fully characterize the HAE gastro protective effect. ResultsHAE (100 and 200 mg/kg) was able to protect mucosa against ethanol gastropathy in presence of three (naloxone, indomethacin and L-NAME) of four antagonist/inhibitor tools. The HAE effect was reversed only by yohimbine, showing the alpha-2 adrenoceptors participation on gastro protective effect of this extract. HAE histological characteristics, NP-SH and Hb were compatible with the protective effects. ConclusionsHAE possesses gastroprotective effects in an ethanol-induced gastropathy model in mice, corroborating the traditional use of this family of plants to treat gastric disorders. This activity is mediated by alpha-2 adrenoceptors activation, but not by nitric oxide release, opioid receptor activation or prostaglandin synthesis. HAE also has antioxidant activity that is thought to either play a role in this biological activity or to be a byproduct of alpha-2 adrenergic complex activation.

Gastroprotective Activity of Sterculia striata A. St. Hil. & Naudin (Malvaceae) in Rodents

The Sterculia striata ethanolic extract (Ss-EtOH) inhibited gastric lesions induced by ethanol, HCl/ethanol, and ischemia/reperfusion, but not those induced by indomethacin, and did not alter the gastric secretion. Ss-EtOH restored the catalase activity and content of nonprotein sulfhydryl groups in the stomach of mice treated with ethanol. The gastroprotection induced by Ss-EtOH in the ethanol-induced gastric lesion model was abolished by N(G)-nitroL-arginine methyl ester (L-NAME) pretreatment, suggesting the involvement of nitric oxide and antioxidant compounds, but not prostaglandins, in this activity. Lupeol obtained from Ss-EtOH promoted gastroprotection as well as the extract at the same dose, and it must therefore contribute to the observed effects.

Protective Effect of Brazilian Propolis Against Hepatic Oxidative Damage in Rats with Water‐immersion Restraint Stress

In the present study we examined the protective effect of Brazilian propolis against hepatic oxidative damage in rats with water-immersion restraint stress (WIRS) in comparison with that of vitamin E (VE). Fasted rats orally received Brazilian green propolis ethanol extract (BPEE; 10, 50 or 100 mg/kg), VE (250 mg/kg) or vehicle at 30 min before the onset of WIRS. Exposure of vehicle-treated rats to 6 h of WIRS caused liver cell damage, judging from the levels of serum alanine aminotransferase and aspartate aminotransferease, increased hepatic lipid peroxide, NO(x) contents and myeloperoxidase activity, and decreased hepatic non-protein SH, ascorbic acid contents and superoxide dismutase activity. Preadministration of BPEE (50 or 100 mg/kg) or VE to the stressed rats protected against the hepatic damage and attenuated the increased hepatic lipid peroxide and NO(x) contents and myeloperoxidase activity and the decreased hepatic non-protein SH and ascorbic acid contents and superoxide dismutase activity. These protective effects of BPEE (50 mg/kg) were greater than those of BPEE (100 mg/kg) and were almost equal to those of VE. These results indicate that BPEE protects against hepatic oxidative damage in rats exposed to WIRS possibly through its antioxidant and antiinflammatory properties such as VE.

Route-dependent effects of cadmium/cadmium and magnesium acute treatment on parameters of oxidative stress in rat liver

The study was designed to evaluate and compare the effects of single oral (or) and intraperitoneal (i.p.) cadmium (Cd) administration on parameters of oxidative stress in liver of rats. Furthermore, investigation on protective effects of magnesium (Mg) or and i.p. pretreatment on the same parameters was performed. Wistar rats were administrated oral dose of Cd (30mg Cd/kg b.w.)/Cd+Mg (30mg Cd/kg b.w., 50mg Mg/kg b.w.) or i.p. dose of Cd (1.5mg Cd/kg b.w.)/Cd+Mg (1.5mg Cd/kg b.w., 3mg Mg/kg b.w.) and sacrificed after 24h. In liver homogenates superoxide anion, malondialdehyde, non-protein sulfhydryl groups, total sulfhydryl groups content, and superoxide dismutase activity were determined. Cadmium intoxication caused the increase of superoxide anion and malondialdehyde levels and had negative effect on investigated parameters of antioxidant defense system, except on total sulfhydryl groups. The negative effect was more emphasized after i.p. Cd administration. Oral Mg pretreatment induced more pronounced positive effect than Mg given intraperitoneally that can be attributed, at least partly, to Cd and Mg interactions on the level of GIT. On the basis of the obtained results it can be concluded that both Cd and Cd+Mg effects on parameters of oxidative stress in rats liver are route-dependent.

Essential oil of Croton zehntneri and its major constituent anethole display gastroprotective effect by increasing the surface mucous layer

Croton zehntneri, a plant native to northeastern Brazil, is widely used in folk medicine to treat gastrointestinal problems and has rich essential oil content. The effects of the essential oil of Croton zehntneri (EOCZ) and its main constituent anethole on several models of gastric lesions were studied in mice and rats. Oral treatment with EOCZ and anethole, both at doses of 30-300 mg/kg, caused similar and dose-dependent gastroprotection against ethanol- and indomethacin-induced gastric damage, but did not change cold-restraint stress-induced ulcers in rats. Furthermore, EOCZ and anethole (both at 30 and 300 mg/kg) similarly and significantly increased the mucus production by the gastric mucosa, measured by Alcian blue binding, in ethanol-induced ulcer model. However, at the same doses, neither EOCZ nor anethole promoted significant alteration in gastric production of non-protein sulfhydryl groups. In pylorus-ligated model, neither EOCZ nor anethole (both at 30 and 300 mg/kg) had a significant effect on the volume of gastric juice, pH, or total acidity. The results of this study show for the first time that EOCZ possesses a gastroprotective potential, an effect mostly attributed to the action of anethole. This activity is related predominantly to the ability of EOCZ and anethole to enhance the production of gastric wall mucus, an important gastroprotective factor. Furthermore, they suggest that EOCZ has potential therapeutic application for the treatment of gastric ulcers.

Effects of L-2-oxоthiazolidine-4-carboxylic acid on the lung antioxidant defense system in an asthma mouse model

We aim ed to study the effect of a glutathione precursor, L-2-oxothiazolidine-4-carboxylic acid (OTCA), on the lung antioxidant defense system in an animal asthma model. Materials and methods: The study was carried out on 24 female C57BL/6 mice. The mice were divided into 4 treatment groups: group 1 - control group; group 2 - injected with ovalbumin (OVA) and given an OVA inhalant; group 3 - treated with OTCA and phosphate-buffered saline inhalant; and group 4 -injected with OVA and OTCA and given an OVA inhalant. Under sodium pentobarbital anesthesia the animals were killed by exsanguination 48 h after the last inhalation to obtain a lung homogenate. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GP) and the content of nonprotein sulfhydryl (NPSH) groups in lung homogenate were investigated. Results: OVA decreased the activities of SOD (P = 0.007), CAT (P = 0.004), and GP (P = 0.05) and the NPSH content (P = 0.0008) in the lung homogenate compared with the control animals. Treatment with OVA and OTCA (group 4) resulted in a significant increase in the activities of CAT (P = 0.01) and GP (P = 0.05) and the NPSH content (P = 0.002) compared to the OVA group (group 2). Conclusion: OTCA (160 mg/kg) restored the activities of basic enzymes in the lung antioxidant defense system in an OVA-induced asthma mouse model 48 h after the last nebulization.

In Vitroandin VivoAntioxidant Activity of Alfalfa (Medicago sativaL.) on Carbon Tetrachloride Intoxicated Rats

The present study was conducted to determine whether lyophilized aqueous extract of alfalfa, or Medicago sativa L. could exert antioxidant activity against carbon tetrachloride-induced oxidative stress and liver injury in rats. The hepatoprotective activity of alfalfa extract was determined by assessing the levels of serum transaminases, ALP, bilirubin and lipid profile. Further, the effect of the test substance on malondialdehyde (MDA), an end product of lipid peroxidation; antioxidant liver enzyme non-protein sulfhydryl (NP-SH); and total protein (TP) were also studied. Serum transaminase, ALP, bilirubin level, lipid profile and liver MDA were significantly elevated and the antioxidant status in liver NP-SH and TP contents were declined in animals treated with CCl (4) alone. Pretreatment with alfalfa and silymarin for three weeks prior to the administration of CCl (4) significantly prevented the increase in the serum levels of hepatic marker, LDL, VLDL levels enzymes and reduced oxidative stress indicated by elevated NP-SH and TP concentration. The histopathological examination of the livers also showed that the alfalfa extract reduced the incidence of liver lesions induced by CCl (4). The in vitro antioxidant assessment of alfalfa extract on DPPH and carotene-linoleic assays demonstrated a moderate antioxidant potential. Results suggest that the alfalfa extract possesses hepatoprotective and antioxidative stress properties possibly through its antioxidant phytochemical constituents and substantiates its use in various liver disorders as a hepatoprotector.

Antioxidant effect of MnTE-2-PyP on lung in asthma mice model.

Aim. To investigate the effects of MnTE-2-PyP on some markers of antioxidant defence system in asthma mice model. Material and Methods. The animals were divided into four groups: group 1, controls; group 2, injected with ovalbumin, group 3, treated with MnTE-2-PyP, and group 4, treated with ovalbumin and MnTE-2-PyP. The activities of superoxide dismutase, catalase, glutathione peroxidase and nonprotein sulfhydryl groups content (NPSH) were determined in lung homogenate. Results. The activities of superoxide dismutase and catalase in group 2 decreased significantly as compared to control group. The decrease of the same enzymes in group 4 was lower and significant as compared to group 2. Changes in the glutathione peroxidase activity showed a similar dynamics. The NPSH groups content decreased in group 2. In group 4 this decrease was relatively lower as compared to group 2. Conclusions. The application of MnTE-2-PyP mitigated the effects of oxidative stress in asthma mice model.

Arsenate V induced glutathione efflux from human erythrocytes

ObjectiveThe objective of the present study was to investigate if arsenate V exposure results in glutathione efflux from human erythrocytes. ProcedureThe changes in intracellular and extracellular nonprotein sulfhydryl and glutathione levels were determined in arsenate (V) exposed erythrocytes. Presence of any cellular membrane damage was assessed by lactate dehydrogenase activity measurement in the supernatant. ResultsWhen erythrocytes were exposed to 10mM of arsenate (V) for 4h, the intracellular NPSH level decreased to 0.28±0025μmol/ml erythrocyte. In contrast, extracellular nonprotein thiol level was increased to 0.180±0.010μmol/ml erythrocyte in 4h. Extracellular glutathione levels reached to 0.028±0.001, 0.052±0.002, and 0.054±0.004μmol/ml erythrocyte with 1, 5, and 10mM of arsenate (V), respectively. Utilization of MK571 a multi drug resistance-associated protein 1 inhibitor decreased the rate of glutathione efflux from erythrocytes suggesting a role for this membrane transporter in the process. ConclusionThe results of the present study indicate that erythrocytes efflux glutathione when exposed to arsenate (V).

‘Okra’Hibiscus esculentus L.: A study of its hepatoprotective activity

In the present study, an attempt has been made to validate the claimed uses of ‘Okra’Hibiscus esculentus in liver diseases. The preventive action of ethanolic extract of okra (EEO) against liver injury was evaluated in rodents using carbon tetrachloride-induced hepatotoxicity model. EEO, at 250 and 500mg/kg body weight, exerted significant dose-dependent hepatoprotection by decreasing the CCl4-induced elevation of serum SGOT, SGPT, ALP, GGT, cholesterol, triglycerides and malondialdehyde (MDA) non-protein sulfhydryls (NP-SH) and total protein (TP) levels in the liver tissue. A significant reduction was also observed in pentobarbital-induced sleeping time in mice. The hepatoprotective and antioxidant activities of the extract are being comparable to standard silymarin. These findings were supported by histological assessment of the liver biopsy. The ability of okra extract to protect chemically induced liver damage may be attributed to its potent antioxidant property.

Effects of arsenite on glutamate metabolism in primary cultured astrocytes

The aim of this study was to explore the mechanisms that contribute to neurotoxicity induced by arsenite exposure focusing on the alteration of glutamate metabolism in primary cultured astrocytes. The cells were exposed to 0–30μM arsenite for 24h, and then cell viability, intracellular nonprotein sulfhydryl (NPSH) levels, mitochondrial membrane potential, activity of Na+/K+-ATPase, glutamine synthetase (GS) and glutamate transporter (GLAST and GLT-1), and protein expression of GS, GLAST and GLT-1 were examined. Compared with those in control, exposure to arsenite resulted in damages of astrocytes in a concentration dependent manner, which were shown by cell viabilities, and supported by morphological observation, mitochondrial membrane potential and intracellular NPSH levels. On the other hand, activities and protein expression of GS, GLAST and GLT-1 were significantly inhibited by arsenite exposure. Moreover, protein expression of GLAST and activities of GS were much more sensitive to arsenite. However, activities of Na+/K+-ATPase were not influenced obviously by arsenite exposure. In conclusion, findings from this study indicated that exposure to arsenite could inhibit glutamate metabolism in astrocytes, which might be related to arsenic-induced neurotoxicity.

Ameliorative Effect of Grewia tenax (Forssk) Fiori Fruit Extract on CCl4–Induced Oxidative Stress and Hepatotoxicity in Rats

The ethanol extract of Grewia tenax (GTE) fruit was tested for possible efficacy against carbon tetrachloride (CCl(4)) induced liver toxicity in Wistar albino rats. GTE at doses of 250 and 500 mg/kg were administered orally to CCl(4)-treated rats. Acute toxicity test and sleeping time determination were done with mice. The results showed that oral administration of GTE for 3 wk to rats significantly reduced the CCl(4)-induced elevated levels of serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, gamma-glutamyl transferase, alkaline phosphatase, bilirubin, cholesterol, high-density lipoproteins, low-density lipoproteins, very low density lipoproteins, and triglycerides. Moreover, it was found that the treatment with GTE significantly elevated the hemoglobin level in serum and increased the nonprotein sulfhydryl and total protein contents in the liver tissue, and a significant diminution was observed in the CCl(4)-induced elevated levels of malondialdehyde in the liver tissue. The biochemical findings were supported by an evaluation with liver histopathology. Pentobarbital-induced prolongation of narcolepsy in mice was shortened significantly by the extract. The observed hepatoprotective effect is believed to occur due to antioxidant properties of the contents of G. tenax extract, which may provide a new drug to be used for fighting liver diseases and it validates its folkloric use in anemic and other conditions.