NPSH Levels Research Articles

Effect of piracetam and vitamin E on phosphamidon-induced impairment of memory and oxidative stress in rats

Organophosphate pesticides, such as phosphamidon (PHOS), have been shown to adversely affect memory and induce oxidative stress after both acute and chronic exposure. The present study was therefore designed to investigate the effects of piracetam (PIR) and vitamin E on PHOS-induced modulation of cognitive function and oxidative stress in rats. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of malondialdehyde (MDA) and nonprotein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and a prolongation of TL in the PHOS (1.74 mg/kg/day per oral; p.o.)-treated group at weeks 6 and 8, as compared to the control group. Administration of PIR (600 mg/kg/day p.o.) or vitamin E (125 mg/kg/day p.o.) for 2 weeks antagonized the effect of PHOS on SDL as well as TL. PHOS per se produced a significant increase in brain MDA levels and a decrease in brain NP-SH levels, whereas administration of PIR (600 mg/kg/day p.o.) or vitamin E (125 mg/kg/day p.o.) attenuated these effects. Thus, the results of the study showed that both PIR and vitamin E attenuated the cognitive dysfunction and oxidative stress induced by PHOS in the rat brain.

外源钙对黑藻抗镉胁迫能力的影响

Heavy metal contamination is an ever-increasing worldwide issue due to its toxic effects on plant metabolism and public health.Cadmium(Cd),an environmental stressor considering its toxicity,persistence and accumulation in biota,is widespread in the aquatic environment.As an essential macroelement,calcium(Ca) plays a crucial role in regulating the growth and development in plants,and also has been shown to alleviate heavy metal toxicity in many plants.Hydrilla verticillata(L.f.) Royle,a common submerged macrophyte as a potential accumulator of heavy metals,distributes universally and grows at a rapid rate.In the present study,it was chosen as the experimental material to investigate whether application of exogenous Ca enhanced the resistance of H.verticillata to cadmium stress.To address this issue,the effects of exogenous Ca application(20 mmol/L Ca) on the Cd accumulation,mineral nutrition,photosynthetic pigments,soluble protein,osmolytes(proline and soluble sugar),antioxidant capacity,non-protein thiols(NP-SH) and phytochelatins(PCs) of H.verticillata under 0.01 mmol/L Cd stress were analyzed.The results demonstrated that,(1) Cd stress induced a substantial accumulation of Cd and resulted in serious imbalance of nutrient elements,such as inhibiting the absorption of P,K,Fe,Cu and Mn significantly,whereas exogenous addition of Ca significantly reduced the accumulation of Cd by 50.24% and effectively reversed the Cd-induced imbalance of nutrient elements in H.verticillata.(2) Cd treatment severely reduced chlorophyll concentration,chlorophyll a/b ratio and soluble protein content,as well as the levels of total antioxidant capacity(T-AOC) and micromolecule antioxidants such as reduced glutathione(GSH) and ascorbic acid(AsA).Exogenous application of Ca markedly retarded the degradation of photosynthetic pigments and promoted the synthesis of soluble protein in Cd-treated H.verticillata.It also significantly increased the levels of antioxidant capacity of the tested plants.(3) In comparison with the control,Cd treatment induced a massive accumulation of proline significantly in H.verticillata,which was 108.29% higher than that of control.When applied with exogenous Ca,the content of proline displayed 29.39% decline compared with 0.01 mmol/L Cd treatment.However,the effect of Cd on soluble sugar was contrary to that on proline in H.verticillata,which showed a significant reduction under Cd stress.Exogenous Ca alleviated the decline in soluble sugar level efficiently.(4) Cd exposure dramatically induced the production of NP-SH and PCs in H.verticillata compared with the control.By contrast,the addition of Ca drastically decreased the levels of NP-SH and PCs by 12.52% and 26.01% compared to the treatment with 0.01 mmol/L Cd,respectively.In conclusion,our results have shown that the supplement of exogenous Ca in a optimal concentration effectively relieved the phytotoxicity of Cd to H.verticillata by decreasing the excessive accumulation of Cd,retarding the degradation of photosynthetic pigments,promoting the synthesis of soluble protein and soluble sugar,keeping high levels of T-AOC/antioxidants and maintaining the balance of nutrient elements,etc.

Effects of butane-2,3-dione thiosemicarbazone oxime on testicular damage induced by cadmium in mice

Our group of studies investigated the action of butane-2,3-dione thiosemicarbazone oxime against the testicular damage caused by cadmium chloride (CdCl(2)) in mice. Mice received a single injection of CdCl(2 )(5 mg/kg, intraperitoneally) and, after thirty minutes, the oxime (10 mg/kg, subcutaneously) was administered. Twenty four hours after the last administration, the animals were killed by cervical dislocation and the testes and serum were removed for analysis. The parameters determined were δ-aminolevulinate dehydratase (δ-ALA-D), myeloperoxidase (MPO), glutathione-S-transferase (GST) and glutathione peroxidase (GPx) activities. The levels of thiobarbituric acid-reactive substances (TBARS), nonprotein thiols (NPSH), ascorbic acid, cadmium and testosterone were also determined. In addition, histological analysis and cytokines quantification (IL-1, IL-6, IL-10, TNF-α and IFN-γ) were performed. Our results demonstrated that the oxime was effective in restoring the inhibition in δ-ALA-D activity induced by CdCl(2). The activation of MPO and increase in IL-1, IL-6, TNF-α and IFN-γ levels induced by CdCl(2) were also reduced by oxime. IL-10, which was reduced by cadmium, was restored by oxime administration. In addition, the oxime was effective in restoring the increase in TBARS levels and the reduction on NPSH levels induced by CdCl(2). Our results demonstrated that oxime was effective in containing the histological alterations induced by CdCl(2). In addition, oxime was able to increase the testosterone levels, reduced by cadmium exposure. In conclusion, the oxime tested was effective in reducing the testicular damage induced by CdCl(2) in mice. The beneficial effects of this oxime are related to its antioxidant and anti-inflammatory action.

Acceleration of Anaerobic Cysteine Transformations to Sulfane Sulfur Consequent toγ-Glutamyl Transpeptidase Inhibition

Toxicity of drugs and radiation in the cells is largely dependent on the level of thiols. In the present studies, an attempt has been made to inhibit γ-glutamyl transpeptidase (γGT) activity in EAT-bearing animals tissue. We have expected that administration of γGT inhibitors: acivicin and 1,2,3,4-tetrahydroisoquinoline (TIQ) may influence GSH/γ–glutamyl transpeptidase (γGT) system in the regulation of cysteine concentration and anaerobic cysteine metabolism in normal and cancer cells. Development of Ehrlich ascites tumor in mice enhances peroxidative processes, diminishes levels of nonprotein thiols (NPSH) and sulfane sulfur, and lowers activities of enzymes involved in its formation and transfer in the liver and kidney. Although γGT inhibitors further decrease NPSH level, they increase cysteine and sulfane sulfur levels. This means that upon γGT inhibition, cysteine can be efficiently acquired by normal liver and kidney cells via another pathway, that is so productive that sulfane sulfur level and intensity of anaerobic cysteine metabolism even rise.

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).

Melatonin attenuates cognitive dysfunction and reduces neural oxidative stress induced by phosphamidon

Melatonin is an important modulator of nervous system functioning and important neural antioxidant. Organophosphate pesticides like phosphamidon (PHOS) have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. This study was designed to explore the modulation of the effects of PHOS on cognitive function by melatonin (MEL). Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of malondialdehyde (MDA) and nonprotein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and prolongation of TL in the PHOS (1.74 mg/kg/day; p.o.)-treated group at weeks 6 and 8 as compared to the control group. Two-week treatment with MEL (5 mg/kg/day; i.p.) antagonized the effect of PHOS on SDL as well as TL. PHOS alone produced a significant increase in the brain MDA levels and decrease in the brain NP-SH levels. Treatment with MEL attenuated the effect of PHOS on oxidative stress. Together the results showed that MEL attenuated the cognitive dysfunction and decreased oxidative stress induced by PHOS in the brain.

Erythrocytic enzymes and antioxidant status in people with type 2 diabetes: Beneficial effect of Syzygium cumini leaf extract in vitro

The aim of the present study was to investigate the effects of Syzygium cumini leaf extract (ASc), on Adenosine deaminase (ADA) and Acetylcholinesterase (AChE) activities, and also on oxidative stress parameters in erythrocytes hemolysates (RBCs) and erythrocytes membranes (ghosts) from type 2 diabetics patients (Type 2 DM) under in vitro conditions. Non protein thiol groups (NP-SH), AChE, Catalase (CAT) and Superoxide Dismutase (SOD) activities were measure in RBCs. Further, ADA activity, Thiobarbituric Acid-Reactive Substances (TBARS) levels and protein thiol groups (P-SH) were estimated in ghosts. Also, P-SH and Vitamin C (VIT C) were measure in plasma sample. The results demonstrated that ADA and AChE activities, besides TBARS levels were higher in erythrocytes of Type 2 DM, while SOD activity and NP-SH levels were decreased when compared to control group. ASc, in vitro, reduced ADA and AChE activities and some parameters of oxidative stress. Furthermore, we observed correlations between VIT C and P-SH levels, ADA activity and P-SH levels, as well as NP-SH and TBARS levels in diabetics. The results suggest that ASc in vitro is able to promote the reduction of inflammation and oxidative stress parameters, and act against biochemical changes occurring in Diabetes mellitus (DM).

The effect of the uremic toxin cyanate (CNO−) on anaerobic cysteine metabolism and oxidative processes in the rat liver: a protective effect of lipoate

Chronic renal failure (CRF) patients have an increased plasma level of urea, which can be a source of cyanate. This compound can cause protein carbamoylation thereby changing biological activity of proteins. Therefore, in renal failure patients, cyanate can disturb metabolism and functioning of the liver. This work presents studies demonstrating that the treatment of rats with cyanate alone causes the following changes in the liver: (1) inhibition of rhodanese (TST), cystathionase (CST) and 3-mercaptopyruvate sulfotransferase (MPST) activities, (2) decrease in sulfane sulfur level (S*), (3) lowering of nonprotein sulfhydryl groups (NPSH) group level, and (4) enhancement of prooxidant processes (rise in reactive oxygen species (ROS) and malondialdehyde (MDA) level). This indicates that cyanate inhibits anaerobic cysteine metabolism and shows prooxidant action in the liver. Out of the above-mentioned changes, lipoate administered with cyanate jointly was able to correct MDA, ROS and NPSH levels, and TST activity. It had no significant effect on MPST and CST activities. It indicates that lipoate can prevent prooxidant cyanate action and cyanate-induced TST inhibition. These observations can be promising for CRF patients since lipoate can play a dual role in these patients as an efficient antioxidant defense and a protection against cyanate and cyanide toxicity.

Effect of progesterone on phosphamidon-induced impairment of memory and oxidative stress in rats

Progesterone (a neurosteroid) is an important modulator of the nervous system functioning. Organophosphorus pesticides like phosphamidon have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. The present study was therefore designed to investigate the effects of progesterone (PROG) on phosphamidon-induced modulation of cognitive function and oxidative stress in rats. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and prolongation of TL in the phosphamidon (1.74 mg/kg/d; p.o.) treated group at weeks 6 and 8 as compared to the control group. Two weeks treatment with PROG (15 mg/kg/d; i.p.) antagonized the effect of phosphamidon on SDL as well as TL. Phosphamidon alone produced a significant increase in the brain TBARS levels and decrease in the brain NP-SH levels. Treatment with PROG (15 mg/kg/d; i.p.) attenuated the effect of phosphamidon on oxidative stress. Together, the results showed that progesterone attenuated the cognitive dysfunction and increased oxidative stress induced by phosphamidon in the brain.

Clomipramine Treatment and Repeated Restraint Stress Alter Parameters of Oxidative Stress in Brain Regions of Male Rats

This study aimed to compare the effects of repeated restraint stress alone and the combination with clomipramine treatment on parameters of oxidative stress in cerebral cortex, striatum and hippocampus of male rats. Animals were divided into control and repeated restraint stress, and subdivided into treated or not with clomipramine. After 40 days of stress and 27 days of clomipramine treatment with 30 mg/kg, the repeated restraint stress alone reduced levels of Na(+), K(+)-ATPase in all tissues studied. The combination of repeated restraint stress and clomipramine increased the lipid peroxidation, free radicals and CAT activity as well as decreased levels of NP-SH in the tissues studied. However, Na(+), K(+)-ATPase level decreased in striatum and cerebral cortex and the SOD activity increased in hippocampus and striatum. Results indicated that clomipramine may have deleterious effects on the central nervous system especially when associated with repeated restraint stress and chronically administered in non therapeutic levels.

Effect of Vernonia cognata on oxidative damage induced by ethanol in rats

Free radicals production and oxidative stress play a central role in injuries caused by ethanol (EtOH) on gastric mucosal. Thus, strategies to counteract EtOH toxicity are highly desirable. This study was aimed at evaluating whether Vernonia cognata extract would reduce EtOH effects in rats. Rats received Vernonia cognata extract (0, 1 and 2 g/kg bw, by gavage) 1 hour after EtOH had been administered (0 or 70%, 0.5 mL/100 g bw, by gavage) and were killed 1 hour after Vernonia cognata extract administration. The stomach was removed for macroscopic and histopathological evaluation, as well as, oxidative stress markers such as lipoperoxidation (LPO) and non-protein thiol groups (NPSH) levels and catalase (CAT) activity. EtOH acute exposure increased LPO and decreased NPSH levels and CAT activity along with macroscopic and microscopic lesions in gastric tissue, confirming the involvement of oxidative stress in EtOH toxicity. Vernonia cognata extract attenuated oxidative and histopathological features induced by EtOH at all evaluated doses. Moreover, both studied doses of Vernonia cognata extract caused an increase in NPSH levels per se. However, only the dose of 2 g/kg reverted all macroscopic changes caused by EtOH toxicity. The protective effect of the extract could be attributed to antioxidant molecules present in the extract, such as flavonoids and phenolic acids, which were quantified by high performance liquid chromatography (HPLC). Thus, an antioxidant effect of the extract leads to a protection on gastric tissue. Our results indicate that Vernonia cognata hydroethanolic extract could have a beneficial role against EtOH toxicity by preventing oxidative stress and gastric tissue injury.

Oxidative stress-mediated inhibition of brain creatine kinase activity by methylmercury

Methylmercury (MeHg), a potent neurotoxicant, easily passes through the blood–brain barrier and accumulates in brain causing severe irreversible damage. However, the underlying neurotoxic mechanisms elicited by MeHg are still not completed defined. In this study, we aimed to investigate the in vitro toxic effects elicited by crescent concentrations (0–1500 μM) of MeHg on creatine kinase (CK) activity, thiol content (NPSH) and protein carbonyl content (PCC) in mouse brain preparations. In addition, CK activity, MTT reduction and DCFH-DA oxidation (reactive oxygen species (ROS) formation) were also measured in C6 glioma cell linage. CK activity was severely reduced by MeHg treatment in mouse brain preparations. This inhibitory effect was positively correlated to the MeHg-induced reduction of NPSH levels and increment in PCC. Moreover, the positive correlation between brain CK activity and NPSH levels was observed at either 15 or 60 min of MeHg pre-incubation. In addition, MeHg-treated C6 cells showed also a significant inhibition of CK activity at MeHg concentrations, as low as, 50 μM in parallel to reduced mitochondrial function and increased ROS production. Taking together, these data demonstrate that MeHg severely affects CK activity, an essential enzyme for brain energy buffering to maintain cellular energy homeostasis. This effect appears to be mediated by oxidation of thiol groups that might cause subsequent oxidative stress.

Involvement of catalase in the protective effect of binaphthyl diselenide against renal damage induced by glycerol

In the present study, the protective effect of binapthyl diselenide [(NapSe) 2] was investigated on glycerol-induced renal damage in rats. Adult male Wistar rats were treated with (NapSe) 2 (50 mg/kg, orally) or vehicle. After 24 h (NapSe) 2 treatment, the animals received an intramuscular injection of glycerol (8 ml/kg, dissolved in saline) or vehicle as a divided dose into the hind limbs. Twenty-four hours afterwards, rats were euthanized and the levels of urea and creatinine were measured in plasma. Non-protein thiol (NPSH) levels and catalase (CAT) activity were evaluated in renal homogenates. Histopathological evaluations were also performed in kidneys of rats. The rats exposed to glycerol presented swelling of the proximal and distal tubules with evidence of cell damage and death. Glycerol-exposed rats presented an increase in renal failure markers (plasmatic urea and creatinine levels) and a reduction in renal CAT activity. No change was observed in NPSH levels in kidneys of rats exposed to glycerol. (NapSe) 2 protected against the alterations caused by glycerol in rats. (NapSe) 2 increased per se NPSH levels (33%) in kidneys of rats. In conclusion, the results demonstrated that treatment with (NapSe) 2 protected against renal damage induced by glycerol in rats, probably due to its antioxidant effect.

Effects of environmental and artificial UV-B radiation on freshwater prawn Macrobrachium olfersi embryos

The recent decrease of the stratospheric ozone has resulted in an increase of ultraviolet-B (UV-B) radiation reaching the Earth's surface. In freshwater ecosystems with transparent water, UV-B rays easily penetrate and potentially cause harmful effects to organisms. In this study, embryos of the prawn Macrobrachium olfersi were used to evaluate the impact of UV-B rays in freshwater environments. We observed three groups of embryos: the first was to assess whether UV-B radiation produced morphological defects and/or biochemical impairments in the laboratory. The second was to check whether embryos with the same impairments as those observed in the laboratory were found in their environment, under natural solar radiation. The third group was the non-irradiated control. The embryos irradiated with 310 mW cm −2 UV-B for 30 min showed morphological alterations similar to those observed in embryos from the environmental control group. The most important effects of the UV-B radiation observed in M. olfersi embryos were morphological (1.2% of the total number of embryos from the environment and 2.8% of the total number of irradiated embryos), pigmentation changes in the eyes (78.0% of the total number of embryos from the environment and 98.9% of the total number of irradiated embryos), and disruption of the chromatophores (46.9% of the total number of embryos from the environment and 95.5% of the total number of irradiated embryos). We also observed an increase in egg volume, which was accompanied by a significant increase in water content in UV-B irradiated groups when compared with aquaria control embryos. In addition, a significant decrease in the mitotic index in eggs exposed to UV-B radiation was detected (0.17 for the embryos from the aquaria control, 0.10 for the embryos of the environmental control, and 0.04 for the irradiated groups). The low levels of NPSH and high levels of TBARS indicated that UV-B rays directly compromised the antioxidant function of the embryonic cells, leading to oxidative stress. Our combined morphological and biochemical analyses revealed important effects induced by UV-B on M. olfersi embryos, and the results suggest that the recent changes in global conditions may have injurious effects, at least on the embryos of freshwater prawns.

The detoxification of lead in Sedum alfredii H. is not related to phytochelatins but the glutathione

Two ecotypes of S. alfredii [Pb accumulating (AE) and Pb non-accumulating (NAE)] differing in their ability in accumulating Pb were exposed to different Pb levels to evaluate the effects on plant length, photosynthetic pigments, antioxidant enzymes (SOD and APX), cysteine, non-protein thiols (NP-SH), phytochelatins (PCs) and glutathione (GSH) vis-à-vis Pb accumulation. Both ecotypes showed significant Pb accumulation in roots, however only the AE showed significant Pb accumulation in shoots. We found that both AE and NAE of S. alfredii-induced biosynthesis of GSH rather than phytochelatins in their tissue upon addition of even high Pb levels (200 μM). Root and shoot length were mostly affected in both ecotypes after addition of higher Pb concentrations and on longer durations, however photosynthetic pigments did not alter upon addition of any Pb treatment. Both superoxide dismutase (SOD) and ascorbate peroxidase (APX) activities of AE were higher than NAE. The levels of cysteine and NP-SH were also higher in AE than in NAE. Hence, the characteristic Pb accumulation of ecotypes differed presumably in relation to their capacity for detoxification of Pb. These results suggest that enzymatic and non-enzymatic antioxidants play a key role in the detoxification of Pb-induced toxic effects in Sedum alfredii. This plant can be used as an indicator species for Pb contamination.

High‐fat diet and hydrochlorothiazide increase oxidative stress in brain of rats

This study evaluated the effect of possible synergic interaction between high fat diet (HF) and hydrochlorothiazide (HCTZ) on biochemical parameters of oxidative stress in brain. Rats were fed for 16 weeks with a control diet or with an HF, both supplemented with different doses of HCTZ (0.4, 1.0, and 4.0 g kg(-1) of diet). HF associated with HCTZ caused a significant increase in lipid peroxidation and blood glucose levels. In addition, HF ingestion was associated with an increase in cerebral lipid peroxidation, vitamin C and non-protein thiol groups (NPSH) levels. There was an increase in vitamin C as well as NPSH levels in HCTZ (1.0 and 4.0 g kg(-1) of diet) and HF plus HCTZ groups. Na(+)-K(+)-ATPase activity of HCTZ (4.0 g kg(-1) of diet) and HCTZ plus HF-fed animals was significantly inhibited. Our data indicate that chronic intake of a high dose of HCTZ (4 g kg(-1) of diet) or HF change biochemical indexes of oxidative stress in rat brain. Furthermore, high-fat diets consumption and HCTZ treatment have interactive effects on brain, showing that a long-term intake of high-fat diets can aggravate the toxicity of HCTZ.

Involvement of non-enzymatic antioxidant defenses in the protective effect of diphenyl diselenide on testicular damage induced by cadmium in mice

The involvement of non-enzymatic antioxidant defenses in the protective effect of diphenyl diselenide (PhSe) 2 on testicular damage caused by cadmium in mice was investigated. Mice received a single dose of CdCl 2 (5 mg/kg, intraperitoneally). Thirty minutes after the CdCl 2 injection, they received a single oral dose of (PhSe) 2 (400 μmol/kg). Twenty-four hours after CdCl 2 administration, blood samples were collected and mice were killed and had their testes dissected. Parameters in plasma (aspartate (AST) and alanine (ALT) aminotransferases and lactato dehydrogenase (LDH) activities as well as creatinine levels) were determined. The activity of δ-aminolevulinate dehydratase (δ-ALA-D), the levels of thiobarbituric acid-reactive substances (TBARS), ascorbic acid and nonprotein thiols (NPSH) and histological analysis were determined in collected samples. Results demonstrated that (PhSe) 2 protected against toxicity induced by CdCl 2 on δ-ALA-D activity, ascorbic acid and NPSH levels. (PhSe) 2 protected against the increase in plasma AST, ALT and LDH activities caused by CdCl 2. Testes of mice exposed to CdCl 2 showed marked histopathological alterations that were ameliorated by administration of (PhSe) 2. (PhSe) 2 protected against toxicity induced by CdCl 2 in testes of mice. Ascorbic acid and NPSH, non-enzymatic antioxidant defenses, are involved in the protective effect of (PhSe) 2 against testicular damage caused by CdCl 2 in mice.

Reversal of propoxur-induced impairment of step-down passive avoidance, transfer latency and oxidative stress by piracetam and ascorbic acid in rats

Propoxur, a carbamate pesticide has been shown to adversely affect memory and induce oxidative stress. The present study was designed to correlate the effect of propoxur, piracetam (a nootropic drug) and ascorbic acid (an antioxidant) on oxidative stress and cognitive function. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on elevated plus maze. Oxidative stress was assessed by examining brain malondialdehyde (MDA) and non-protein thiol (NP-SH) levels. A significant reduction in SDL and prolongation of TL was found for the propoxur-treated group at weeks 6 and 7 as compared with control ( p < 0.001). One week treatment by piracetam (400 mg/kg/d, i.p.) or ascorbic acid (120 mg/kg/d, i.p.) antagonized the effect of propoxur on SDL as well as TL. Both piracetam and ascorbic acid attenuated the propoxur-induced increase in brain MDA levels and decrease in brain NP-SH levels. Results of the present study show that ascorbic acid and piracetam have the potential to reverse cognitive dysfunction and oxidative stress induced by propoxur in the brain.

Is propylene oxide induced cell proliferation in rat nasal respiratory epithelium mediated by a severe depletion of water-soluble non-protein thiol?

Propylene oxide (PO) concentrations ≥300 ppm induced cell proliferation and tumors in rat nasal respiratory epithelium (NRE). Cell proliferation was suggested to result from depletion of glutathione (GSH) in NRE. In order to substantiate this hypothesis, cell proliferation – measured by bromodeoxyuridine incorporation into DNA of the epithelium lining middle septum, dorsal medial meatus, and medial and lateral surfaces of the nasoturbinate in transverse nasal sections taken immediately posterior to the upper incisor teeth – and water-soluble non-protein thiol (NPSH) in NRE were determined after exposing male Fischer 344 rats to 50 ppm, 100 ppm, 200 ppm, or 300 ppm PO (6 h/day, 3 days). Both parameters were also investigated after treating rats for 3 days with diethylmaleate (DEM; 2 × 250 mg/kg/day or 500 + 150 mg/kg/day) or buthionine sulfoximine (BSO; 500 mg/kg/day). Exposure to 50 ppm PO and treatment with 2 × 250 mg/kg/day DEM resulted in NPSH levels approximating 50% and 80% of the level in untreated controls, respectively. Cell proliferation did not increase. After exposures to ≥100 ppm PO or treatment with BSO or 500 + 150 mg/kg/day DEM, NPSH was depleted to ≤1/3 of the control level and cell proliferation increased 2.0–3.7-fold the control value. In conclusion, profound perturbation of the GSH status may represent a crucial step in PO induced rat nasal tumorigenicity.

Diphenyl diselenide, a simple organoselenium compound, decreases methylmercury-induced cerebral, hepatic and renal oxidative stress and mercury deposition in adult mice

Oxidative stress has been pointed out as an important molecular mechanism in methylmercury (MeHg) intoxication. At low doses, diphenyl diselenide ((PhSe) 2), a structurally simple organoselenium compound, has been shown to possess antioxidant and neuroprotective properties. Here we have examined the possible in vivo protective effect of diphenyl diselenide against the potential pro-oxidative effects of MeHg in mouse liver, kidney, cerebrum and cerebellum. The effects of MeHg exposure (2 mg/(kg day) of methylmercury chloride 10 ml/kg, p.o.), as well as the possible antagonist effect of diphenyl diselenide (1 and 0.4 mg/(kg day); s.c.) on body weight gain and on hepatic, cerebellar, cerebral and renal levels of thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH), ascorbic acid content, mercury concentrations and activities of antioxidant enzymes (glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD)) were evaluated after 35 days of treatment. MeHg caused an increase in TBARS and decreased NPSH levels in all tissues. MeHg also induced a decrease in hepatic ascorbic acid content and in renal GPx and CAT activities. Diphenyl diselenide (1 mg/kg) conferred protection against MeHg-induced hepatic and renal lipid peroxidation and at both doses prevented the reduction in hepatic NPSH levels. Diphenyl diselenide also conferred a partial protection against MeHg-induced oxidative stress (TBARS and NPSH) in liver and cerebellum. Of particular importance, diphenyl diselenide decreased the deposition of Hg in cerebrum, cerebellum, kidney and liver. The present results indicate that diphenyl diselenide can protect against some toxic effects of MeHg in mice. This protection may be related to its antioxidant properties and its ability to reduce Hg body burden. We posit that formation of a selenol intermediate, which possesses high nucleophilicity and high affinity for MeHg, accounts for the ability of diphenyl diselenide to ameliorate MeHg-induced toxicity.