Influence of diphenyl diselenide on chlorpyrifos-induced toxicity in Drosophila melanogaster

Exposure to chlorpyrifos (CPF) poses several harmful effects to human and animal health. The present study investigated the influence of diphenyl diselenide (DPDS) on CPF-induced toxicity in Drosophila melanogaster. Firstly, the time course lethality response of virgin flies (2- to 3-day-old) to CPF (0.075–0.6 μg/g) and DPDP (5–40 μmol/kg) in the diet for 28 consecutive days were investigated. Subsequently, the protective effect of DPDS (10, 20 and 40 μmol/kg) on CPF (0.15 μg/g)-induced mortality, locomotor deficits, neurotoxicity and oxidative stress was assessed in a co-exposure paradigm for 7 days. Results showed that CPF exposure significantly decreased the percent live flies in a time- and concentration-dependent manner, whereas the percent live flies with DPDS treatment was not statistically different from control following 28 days of treatment. In the co-exposure study, CPF significantly increased flies mortality while the survivors exhibited significant locomotor deficits with decreased acetylcholinesterase (AChE) activity. Dietary supplementation with DPDS was associated with marked decrease in mortality, improvement in locomotor activity and restoration of AChE activity in CPF-exposed flies. Moreover, CPF exposure significantly decreased catalase and glutathione-S-transferase activities, total thiol level with concomitant significant elevation in the levels of reactive oxygen species and thiobarbituric acid reactive substances in the head and body regions of the treated flies. Dietary supplementation with DPDS significantly improved the antioxidant status and prevented CPF-induced oxidative stress, thus demonstrating the protective effect of DPDS in CPF-treated flies.     

Protective effects of aloe-emodin on scopolamine-induced memory impairment in mice and H2O2-induced cytotoxicity in PC12 cells

Aloe-emodin (AE) is one of the most important active components of Rheum officinale Baill. The present study aimed to investigate that AE could attenuate scopolamine-induced cognitive deficits via inhibiting acetylcholinesterase (AChE) activity and modulating oxidative stress. Kunming (KM) mice were received intraperitoneal injection of scopolamine (2 mg/kg) to induce cognitive impairment. Learning and memory performance were assessed in the Morris water maze (MWM). After behavioral testing, the mice were sacrificed and their hippocampi were removed for biochemical assays (superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), AChE and acetylcholine (ACh)). In vitro, we also performed the AChE activity assay and H₂O₂-induced PC12 cells toxicity assay. After 2 h exposure to 200 μM H₂O₂ in PC12 cells, the cytotoxicity were evaluated by cell viability (MTT), nitric oxide (NO)/lactate dehydrogenase (LDH) release and intracellular reactive oxygen species (ROS) production. Our results confirmed that AE showed significant improvement in cognitive deficit in scopolamine-induced amnesia animal model. Besides, it increased SOD, GPx activities and ACh content, while decreased the level of MDA and AChE activity in AE treated mice. In addition, AE was found to inhibit AChE activity (IC₅₀ = 18.37 μg/ml) in a dose-dependent manner. Furthermore, preincubation of PC12 cells with AE could prevent cytotoxicity induced by H₂O₂ and reduce significantly extracellular release of NO, LDH and intracellular accumulation of ROS. The study indicated that AE could have neuroprotective effects against Alzheimer’s disease (AD) via inhibiting the activity of AChE and modulating oxidative stress.     

S-nitrosoglutathione-induced toxicity in Drosophila melanogaster: Delayed pupation and induced mild oxidative/nitrosative stress in eclosed flies

The toxicity of the nitric oxide donor S-nitrosoglutathione (GSNO) was tested on the Drosophila melanogaster model system. Fly larvae were raised on food supplemented with GSNO at concentrations of 1.0, 1.5 or 4.0 mM. Food supplementation with GSNO caused a developmental delay in the flies. Biochemical analyses of oxidative stress markers and activities of antioxidant and associated enzymes were carried out on 2-day-old flies that emerged from control larvae and larvae fed on food supplemented with GSNO. Larval exposure to GSNO resulted in lower activities of aconitase in both sexes and also lower activities of catalase and isocitrate dehydrogenase in adult males relative to the control cohort. Larval treatment with GSNO resulted in higher carbonyl protein content and higher activities of glucose-6-phosphate dehydrogenase in males and higher activities of superoxide dismutase and glutathione-S-transferase in both sexes. Among the parameters tested, aconitase activity and developmental end points may be useful early indicators of toxicity caused by GSNO.     

Antioxidant responses of Propylaea japonica (Coleoptera: Coccinellidae) exposed to high temperature stress

Temperature is one of the most important environmental factors, and is responsible for a variety of physiological stress responses in organisms. Induced thermal stress is associated with elevated reactive oxygen species (ROS) generation leading to oxidative damage. The ladybeetle, Propylaea japonica (Thunberg) (Coleoptera: Coccinellidae), is considered a successful natural enemy because of its tolerance to high temperatures in arid and semi-arid areas in China. In this study, we investigated the effect of high temperatures (35, 37, 39, 41 and 43 °C) on the survival and activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidases (POD), glutathione-S-transferases (GST), and total antioxidant capacity (TAC) as well as malondialdehyde (MDA) concentrations in P. japonica adults. The results indicated that P. japonica adults could not survive at 43 °C. CAT, GST and TAC were significantly increased when compared to the control (25 °C), and this played an important role in the process of antioxidant response to thermal stress. SOD and POD activity, as well as MDA, did not differ significantly at 35 and 37 °C compared to the control; however, there were increased levels of SOD, POD and MDA when the temperature was above 37 °C. These results suggest that thermal stress leads to oxidative stress and antioxidant enzymes play important roles in reducing oxidative damage in P. japonica adults. This study represents the first comprehensive report on the antioxidant defense system in predaceous coccinellids (the third trophic level). The findings provide useful information for predicting population dynamics and understanding the potential for P. japonica as a natural enemy to control pest insects under varied environmental conditions.     

Effect of S-allylcysteine,a sulphur containing amino acid on iron metabolism in streptozotocin induced diabetic rats

It is suggested that iron may play a role in the pathogenesis of diabetes. Iron is not only chaperoned through its essential functional pathways, but it also causes damage to biological systems by catalyzing the production of reactive oxygen species. So, the parenchymal tissues of several organs are subject to cell injury and functional insufficiency due to excess deposition of iron. The present study investigated the effects of S-allylcysteine (SAC), a sulphur containing amino acid derived from garlic on the changes in iron metabolism induced by oxidative stress in tissues, as well as on serum biochemical parameters of streptozotocin (STZ)-induced diabetic rats. SAC was administered orally for 45 days to control and experimental diabetic rats. The effects of SAC on glucose, insulin, serum iron, ferritin, transferrin, serum bilirubin, heart heme oxygenase activity (HO) and δ-aminolevulinicacid dehydratase activity (δ-ALA-D) in liver and kidneys were studied. The levels of glucose, iron, ferritin, bilirubin and HO in liver were increased significantly (p < 0.05) whereas the levels of insulin, transferrin and δ-ALA-D in tissues were decreased in diabetic rats. Administration of SAC to diabetic rats showed a decrease in blood glucose, iron, ferritin, bilirubin and HO. In addition, the levels of insulin, transferrin and δ-ALA-D activity in tissues were increased in SAC treated diabetic rats. These findings suggest that S-allylcysteine could have a protective effect against alterations in oxidative stress induced iron metabolism in the diabetic state which was evidenced by the capacity of this natural antioxidant to modulate parameters of iron metabolism.     

Protective effect of Piper betle leaf extract against cadmium-induced oxidative stress and hepatic dysfunction in rats

The present study was undertaken to examine the attenuative effect of Piper betle leaf extract (PBE) against cadmium (Cd) induced oxidative hepatic dysfunction in the liver of rats. Pre-oral supplementation of PBE (200 mg/kg BW) treated rats showed the protective efficacy against Cd induced hepatic oxidative stress. Oral administration of Cd (5 mg/kg BW) for four weeks to rats significantly (P > 0.05) elevated the level of serum hepatic markers such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), bilirubin (TBRNs), oxidative stress markers viz., thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), protein carbonyls (PC) and conjugated dienes (CD) and significantly (P > 0.05) reduced the enzymatic antioxidants viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) and non-enzymatic antioxidants Viz., reduced glutathione (GSH), total sulfhydryls (TSH), vitamin C and vitamin E in the liver. Pre-oral supplementation of PBE (200 mg/kg BW) in Cd intoxicated rats, the altered biochemical indices and pathological changes were recovered significantly (P > 0.05) which showed ameliorative effect of PBE against Cd induced hepatic oxidative stress. From the above findings, we suggested that the pre-administration of P. betle leaf extract exhibited remarkable protective effects against cadmium-induced oxidative hepatic injury in rats.     

Changes in proline accumulation and antioxidative enzyme activities in Groenlandia densa under cadmium stress

In this study an experiment was carried out to study the process of stress adaptation in Groenlandia densa (opposite-leaved pondweed) grown under cadmium stress (0–20 mg L^?1 Cd). The results showed that Cd concentrations in plants increased with increasing Cd supply levels and reached a maximum of 0.43 mg kg^?1 DW at 0.5 mg L^?1 Cd concentrations. The level of photosynthetic pigments and soluble proteins decreased only upon exposure to high Cd concentrations. At the same time, the level of malondialdehyde (MDA) increased with increasing Cd concentration. These results suggested an alleviation of stress that was presumably the result of by antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione S-transferase (GST) as well as ascorbate peroxidase (APX), which increased linearly with increasing Cd levels. Cellular antioxidants levels showed a decline suggesting a defensive mechanism to protect against oxidative stress caused by Cd. In addition, the proline content in G. densa increased with increasing cadmium levels. These findings suggest that G. densa is equipped with an efficient antioxidant mechanism against Cd-induced oxidative stress which protects the plant's photosynthetic machinery from damage.Our present work concluded that G. densa has a high level of Cd tolerance and accumulation. We also found that moderate Cd treatment (0.05–5 mg L^?1 Cd) alleviated oxidative stress in plants, while the addition of higher amounts of Cd (10–20 mg L^?1) could cause an increasing generation of ROS, which was effectively scavenged by the antioxidative system.     

Role of Bacopa monnieri in the temporal regulation of oxidative stress in clock mutant (cryb) of Drosophila melanogaster

Accruing evidences imply that circadian organization of biochemical, endocrinological, cellular and physiological processes contribute to wellness of organisms and in the development of pathologies such as malignancy, sleep and endocrine disorders. Oxidative stress is known to mediate a number of diseases and it is notable to comprehend the orchestration of circadian clock of a model organism of circadian biology, Drosophila melanogaster, under oxidative stress. We investigated the nexus between circadian clock and oxidative stress susceptibility by exposing D. melanogaster to hydrogen peroxide (H₂O₂) or rotenone; the reversibility of rhythms following exposure to Bacopa monnieri extract (ayurvedic medicine rich in antioxidants) was also investigated. Abolishment of 24 h rhythms in physiological response (negative geotaxis), oxidative stress markers (protein carbonyl and thiobarbituric acid reactive substances) and antioxidants (superoxide dismutase, catalase, glutathione-S-transferase and reduced glutathione) were observed under oxidative stress. Furthermore, abolishment of per mRNA rhythm in H₂O₂ treated wild type flies and augmented susceptibility to oxidative stress in clock mutant (cry^b) flies connotes the role of circadian clock in reactive oxygen species (ROS) homeostasis. Significant reversibility of rhythms was noted following B. monnieri treatment in wild type flies than cry^b flies. Our experimental approach revealed a relationship involving oxidative stress and circadian clock in fruit fly and the utility of Drosophila model in screening putative antioxidative phytomedicines prior to their use in mammalian systems.     

Are fish in hot water? Effects of warming on oxidative stress metabolism in the commercial species Sparus aurata

Climate change is disturbing marine biological processes, and impacting goods and services provided to society. Physiological studies are a major contributor to the improvement of biological forecasting in the context of climate change. Oxidative stress biomarkers are useful tools to assess the metabolic status and health of organisms, improving management of wild and cultured populations. The aims of this study were to assess the health status and vulnerability of Sparus aurata juveniles toward ocean warming and heat wave events by (1) exposing fish to a thermal ramp from 18 °C until their Critical Thermal Maximum (≈35 °C) and (2) quantifying oxidative stress biomarkers in several organs, i.e. lipid peroxidation (LPO), catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), and cytochrome CYP1A. Fish showed signs of oxidative stress in every tissue tested (gills, muscle, liver, brain and intestine), the most affected being muscle and liver, which showed greater increases in LPO. In general, antioxidant enzymes increased their activity: CAT increased in every organ tested, GST increased in every organ except brain (no change) and SOD increased in every organ except intestine (no change) and brain (decrease, probably due to enzyme denaturation). Muscle showed the greatest stress response with a massive increase in GST. Hepatic CYP1A decreased upon warming suggesting that temperature influences detoxifying mechanisms and may affect fish health. These results are significant in the context of climate change and associated impacts on fisheries and aquaculture because over-induction of oxidative stress due to warming can induce health problems, mortality and shortened lifespan.     

Lactating and non-lactating rats differ in sensitivity to HgCl2: Protective effect of ZnCl2

This work investigated zinc (Zn) and mercury (Hg) effects on oxidative parameters, markers of toxicity and metal levels in different tissues from non-lactating rats (NLR) and lactating rats (LR). Adult NLR and LR received ZnCl₂ (27 mg/kg) or saline (0.9%) subcutaneously and after 24 h they received HgCl₂ (5 mg/kg) or saline (0.9%). Twenty four hours later, they were sacrificed and the preparation of biological material and biochemical analyses were performed. With respect to oxidative parameters, Hg exposure decreased kidney total SH levels from NLR and LR and hepatic catalase activity (not statistically significant) in NLR. Zinc pre-treatment partly prevented the decrease of kidney total SH levels in LR. Zinc per se increased hepatic non-protein SH levels of NLR and LR. Regarding toxicity markers, Hg exposure inhibited the δ-aminolevulinic acid dehydratase (δ-ALA-D) activity from kidney and liver of NLR, inhibited serum alanine aminotransferase (ALT) activity of LR and increased serum creatinine and urea levels of NLR and LR. Zinc pre-exposure prevented the enzymatic alterations caused by Hg. NLR and LR Hg exposed presented accumulation of mercury in the kidney, liver, blood and urine. Zinc pre-treatment prevented this accumulation partly in NLR liver and blood and completely in LR kidney and liver. These results show that NLR and LR are differently sensitive to HgCl₂ and that ZnCl₂ showed a promising effect against Hg toxicity.     

Multi-organ toxicological impact of fungicide propiconazole on biochemical and histological profile of freshwater fish Channa punctata Bloch

Fungicides are a pesticide that particularly kills or destroy fungi responsible for several diseases associated to humans and other living organisms. Assessment of toxic effects and mechanisms of fungicide action is important because humans and domesticated animals get exposed to these pesticides through a wide variety of applications. Several fungicides are being used at the large scale for the crop protection from the fungal invasion. Propiconazole (PCZ), a trazole-containing fungicide, is widely used in China and various Asian countries for food crop protection which made it easily to exposed to the aquatic system. Long term usage of PCZ may contaminate the water bodies, but its toxicity to aquatic organisms is not well studied. In this study, freshwater fish, Channa punctata Bloch was exposed to different sub-lethal concentrations of the fungicide, PCZ (0.5 and 5 ppm) for a period of 96 h. Various biochemical assays and histological alterations were measured to determine the organ toxicity caused by PCZ exposure particularly in liver, kidney and gills of the fishes. Compared to the control group, fish exposed to PCZ (96 h) showed marked dose dependent toxicity. The levels of lipid peroxidation (LPO) and protein carbonyls (PC), oxidative stress biomarker of liver, kidney and gills in the experimental group were significantly higher (P < 0.05 and P < 0.001) compared to the control group. Levels of reduced glutathione (GSH) and non-protein thiols (NP-SH) decreased significantly (P <0.05–0.001) in all analyzed intoxicated organs of the PCZ exposed fishes. Activity of glutathione-S-transferase (GST), glutathione peroxidase (GPx) and catalase (CAT) in fungicide treated groups was significantly lowered (P < 0.05–0.001). In addition, histopathological examination in the organs showed significant changes like atrophy of primary and secondary gill lamellae, infiltrations, inflammation, hepatocyte degeneration, vacuolization and necrotic kidney. Thus, PCZ exposure altered the oxidative stress homeostasis and brought about histopathological changes which may serve as potential biomarkers of the PCZ toxicity in the laboratory set-up for potential risk assessment.     

Alterations in the general condition,biochemical parameters and locomotor activity in Cnesterodon decemmaculatus exposed to commercial formulations of chlorpyrifos,glyphosate and their mixtures

The Pampean region, an extensive area of South America is continuously impacted by agricultural activities and the pesticides related to them like chlorpyrifos and glyphosate. Both pesticides have been registered in freshwater bodies of the region. One of the most abundant and widely distributed fish species in Pampean streams is Cnesterodon decemmaculatus, which have to cope with this altered scenario.In the present study the toxicity of Clorfox^® and Roundup Max^®, the commercial formulations of chlorpyrifos and glyphosate, respectively, and their mixture where evaluated using a set of biomarkers at different biological organization levels in fish exposed to relevant environmentally pesticides concentrations. Somatic indexes such as the condition factor (K), and the hepato-somatic index (HSI), the locomotor activity through the distance traveled and the average speed, the enzymatic activities of acetylcholinesterase (AChE) in brain and muscle, catalase (CAT) in muscle and liver, glutathione-S-transferase (GST) in brain, liver, muscle and gills, aspartate amino-transferase (AST), alanine amino-transferase (ALT), AST/ALT ratio and alkaline phosphatase (ALP) in liver were measured on C. decemmaculatus. Adult females were exposed during 6 weeks to the following concentrations: 0.0084 μl/l and 0.00084 μl/l of Clorfox (CF), 0.2 and 2 mg/l of Roundup Max (RM) and all the combinations of these concentrations. The CF exposure caused a decrease in the condition factor and in the locomotor activity parameters and induced an increase brain AChE, liver CAT activity and AST/ALT ratio. On the other hand, the exposure to RM produced a decrease in liver GST, AST/ALT ratio and ALP activity. Finally, some pesticide combinations decrease general condition and liver GST activities, and increase brain GST and liver ALP activities. Different responses in biomarkers were observed in mixtures treatments, reflecting the complex interactions between these toxics and suggesting a suppressive action of RM on CF effects.Since the concentrations we tested are environmentally relevant and the overall fish health condition was affected, the presence of these pesticides in freshwater systems could impose a risk for populations by causing deleterious effects on C. decemmaculatus in Pampean region.     

Apoptosis of tiger shrimp (Penaeus monodon) haemocytes induced by Escherichia coli lipopolysaccharide

This study was aimed at investigating the toxicity mechanism of lipopolysaccharide (LPS) on Penaeus monodon haemocytes at a cellular level. Reactive oxygen species (ROS) production, nitric oxide (NO) production, non-specific esterase activity, cytoplasmic free-Ca^2 + (CF-Ca^2 +) concentration, DNA damaged cell ratio and apoptotic cell ratio of in vitro LPS-treated haemocytes were measured by flow cytometry. Two concentrations of Escherichia coli LPS (5 and 10 μg mL^? 1) were used. Results showed that ROS production, NO production and CF-Ca^2 + concentration were significantly induced in the LPS-treated haemocytes. Ratio of DNA damaged cell and apoptotic cell increased caused by LPS, while esterase activity increased at the initial 60 min and dropped later. The initial increase in esterase activity suggested that LPS activated the release of esterase, and the later decrease might result from apoptosis. These results indicated that LPS would induce oxidative stress on shrimp haemocytes, and cause Ca^2 + release, DNA damage and subsequently cell apoptosis. This process of ROS/RNS-induced Ca^2 +-mediated apoptosis might be one of the toxicity mechanisms of LPS on shrimp haemocytes.     

Studying the cytotoxicity and oxidative stress induced by two kinds of bentonite particles on human B lymphoblast cells in vitro

The aim of the present study was to evaluate the cytotoxicity and oxidative stress induced by native and active bentonite particles (BPs) on human B lymphoblast cells using seven assays. Our results showed that the order of cytotoxicity was: active BPs > native BPs > quartz particles (DQ-12) > gypsum, according to the IC50 values in CCK-8 assay and neutral red uptake (NRU) assay. The lactate dehydrogenase (LDH) leakage, the proportions of early apoptotic cells, the reactive oxygen species (ROS) generation, the superoxide dismutase (SOD) inhibition and the malondialdehyde (MDA) release in the native and active BPs groups were significantly higher than those in the gypsum and DQ-12 groups (P < 0.05 or P < 0.01). Moreover, the cytotoxicity of active BPs with higher adsorption capacity of phenol was higher than that of native BPs with relatively lower adsorption capacity of phenol. The oxidative stress induced by active BPs was significantly higher than that induced by native BPs (P < 0.05 or P < 0.01). The water-soluble fractions of BPs did not induce the cytotoxicity and ROS generation. These findings indicated that active and native BPs could induce significantly the cytotoxic effects and oxidative stress on human B lymphoblast cells in vitro. The cytotoxic difference between active BPs and native BPs may be associated with the adsorption capacity of BPs and oxidative stress induced by BPs to a certain extent. The insoluble particle fractions may play a main role in the cytotoxic effects and oxidative stress induced by BPs.     

Mutated glutathione S-transferase in combination with reduced glutathione shows a synergistic effect in ameliorating oxidative stress and airway inflammation

Oxidative stress is implicated in the pathogenesis of asthma, and antioxidant levels are reduced in asthma patients. Previously, glutathione S-transferase (GST) with reduced IgE binding suppressed oxidative stress and modulated airway inflammation to some extent in mice. GST catalyzes the quenching of reactive oxygen species by reduced glutathione (GSH) and the absence of any one of them may limit antioxidative behavior. This study evaluates the effects of mutated (m) GST with GSH in combination and individually in limiting oxidative stress and inflammatory responses in a mouse model. BALB/c mice were immunized and challenged with ovalbumin. The mice were treated with mGST, GSH, mGST + GSH, or α-lipoic acid by inhalation and sacrificed to evaluate inflammation and oxidative stress parameters. Treatment with the mGST + GSH combination showed significantly reduced total cell (p < 0.01) and eosinophil (p < 0.01) counts in BALF compared to other groups. The lung inflammation score was lowest for the mGST + GSH group, along with reduced IL-4 (p < 0.01) and OVA-specific IgE compared to the other treatment groups. Oxidative stress as per the lipid peroxidation and 8-isoprostane level in BALF of mGST + GSH mice was reduced significantly compared to the individual antioxidants. In conclusion, mGST in combination with GSH has a synergistic effect in reducing airway inflammation compared to the individual antioxidants and has potential for the treatment of asthma.     

Ganoderma atrum polysaccharide attenuates oxidative stress induced by d-galactose in mouse brain

AimsGanoderma atrum polysaccharide (PSG-1), the main constituent of G. atrum, has been reported to attenuate oxidative stress in vitro. The aim of this study was to investigate whether PSG-1 has a protective effect on the brain against oxidative stress induced by d-galactose (D-gal) in vivo.Main methodsMice were intraperitoneally (i.p.) injected with D-gal (100 mg/kg body weight) once daily for 10 weeks. From the seventh week, D-gal-treated mice received PSG-1 (50, 100, or 150 mg/kg body weight) once daily for the last 4 weeks. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GSH-Rd), and the contents of glutathione (GSH), glutathione disulfide (GSSG) and malondialdehyde (MDA) in the brain were measured using different biochemical methods to evaluate the changes of the antioxidant ability in the PSG-1 treated mice. Apoptosis, reactive oxygen species (ROS) and calcium levels were determined by flow cytometry.Key findingsAdministration of PSG-1 significantly reduced apoptosis in the mouse brain in a dose-dependent manner. PSG-1-evoked reduction of apoptosis was associated with the decrease of MDA and GSSG contents, and the increase of SOD, CAT, GPx and GSH-Rd activities, and GSH contents. PSG-1 treatment was also found to attenuate ROS production and calcium accumulation.SignificancePSG-1 has a potential to be used as a novel therapeutic agent for the protection of aging brain tissue against oxidative damage by modifying the redox system and maintaining calcium homeostasis.     

Roundup disrupts male reproductive functions by triggering calcium-mediated cell death in rat testis and Sertoli cells

Glyphosate is the primary active constituent of the commercial pesticide Roundup. The present results show that acute Roundup exposure at low doses (36 ppm, 0.036 g/L) for 30 min induces oxidative stress and activates multiple stress-response pathways leading to Sertoli cell death in prepubertal rat testis. The pesticide increased intracellular Ca²⁺ concentration by opening L-type voltage-dependent Ca²⁺ channels as well as endoplasmic reticulum IP₃ and ryanodine receptors, leading to Ca²⁺ overload within the cells, which set off oxidative stress and necrotic cell death. Similarly, 30 min incubation of testis with glyphosate alone (36 ppm) also increased ⁴⁵Ca²⁺ uptake. These events were prevented by the antioxidants Trolox and ascorbic acid. Activated protein kinase C, phosphatidylinositol 3-kinase, and the mitogen-activated protein kinases such as ERK1/2 and p38MAPK play a role in eliciting Ca²⁺ influx and cell death. Roundup decreased the levels of reduced glutathione (GSH) and increased the amounts of thiobarbituric acid-reactive species (TBARS) and protein carbonyls. Also, exposure to glyphosate–Roundup stimulated the activity of glutathione peroxidase, glutathione reductase, glutathione S-transferase, γ-glutamyltransferase, catalase, superoxide dismutase, and glucose-6-phosphate dehydrogenase, supporting downregulated GSH levels. Glyphosate has been described as an endocrine disruptor affecting the male reproductive system; however, the molecular basis of its toxicity remains to be clarified. We propose that Roundup toxicity, implicated in Ca²⁺ overload, cell signaling misregulation, stress response of the endoplasmic reticulum, and/or depleted antioxidant defenses, could contribute to Sertoli cell disruption in spermatogenesis that could have an impact on male fertility.     

Design,synthesis and biological evaluation of organophosphorous-homodimers as dual binding site acetylcholinesterase inhibitors

The cluster effect is an effective strategy to explore new lead compounds, and has been successfully applied in rational drug design and screening. A series of novel organophosphorous-homodimers were designed and synthesized based on the dual-site structure characteristics of acetylcholinesterase (AChE). The compounds were evaluated in vitro for their inhibitory activity to AChE extracted from Drosophila melanogaster and Musca domestic. Compound 4H showed an excellent inhibitor activity to both Drosophila melanogaster and Musca domestic with the corresponding IC₅₀ values of 23 and 168 nM, respectively. Meanwhile, its activities against Drosophila melanogaster and Musca domestic AChE were more than 10,00,000 and 100,000-fold higher compared with the parent compound (MH), and was up to 245 and 107-fold higher than those of the positive control omethoate. The molecular docking study revealed that 4H possessed an optimal spacer length and can perfectly fit into the central pocket, active gorge, and peripheral site of DmAChE, and consequently exhibited highly improved inhibitor potency to DmAChE. The bioassay tests showed that 4 series compounds showed prominent insecticidal activities against both Lipaphser erysimi and Tetranychus cinnbarinus at a concentration of 200 mg/L. The insecticide activity of compound 4H was particularly significant that can cause 96% mortality to Tetranychus cinnbarinus after 24 h of treatment.     

Propiconazole induced toxicological alterations in brain of freshwater fish Channa punctata Bloch

Fungicides are a class of pesticides which are used indiscriminately in large amounts and pose a serious threat to the environment. Propiconazole (PCZ) is a systemic foliar fungicide with a broad range of activity. The potential of this fungicide to induce toxicity has not been fully explored. The present study was designed to investigate the dose dependent neurotoxic effect of propiconazole (PCZ), with Channa punctata Bloch as a model organism. Effect of PCZ on the brain specific enzyme activity such as acetylcholinesterase (AChE), monoamine oxidase (MAO) and Na⁺-K⁺-ATPase was determined in the fish brain tissue exposed to sub-lethal concentrations (0.5 and 5 ppm) for 96 h. Also, levels of oxidative stress reflected by various enzymatic and non-enzymatic antioxidants were measured. Neurotransmitter (epinephrine) level was also assessed. PCZ exposure induced oxidative stress as reflected by the significant increase in fish brain lipid peroxidation and protein carbonyl content with decrease in reduced glutathione levels, as well as the significant inhibition of glutathione dependent metabolizing enzymes and CAT activities. In addition, AChE, MAO and Na⁺-K⁺-ATPase activities were significantly lowered along with reduction in epinephrine levels in PCZ exposed fishes than those of the control in a dose dependent manner. Also, histopathological alterations were observed in fish brain of the treated fishes. The results point towards the potential neurotoxicity in the fish caused by PCZ exposure but the application of these findings will need more detailed study before they can be established as special biomarkers for toxicity monitoring the aquatic environment.