Alteration of cholinesterase activity as possible mechanism of silver nanoparticle toxicity

Due to their broad-spectrum antimicrobial activity, silver nanoparticles (AgNPs) have been used in a large number of commercial and medical products. Such proliferated AgNP production poses toxicological and environmental issues which need to be addressed. The present study aimed to investigate the effects of AgNPs on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), important enzymes in areas of neurobiology, toxicology and pharmacology. Three different AgNPs, prepared by the chemical reduction using trisodium citrate, hydroxylamine hydrochloride (Cl-AgNPs), and borohydride following stabilization with poly(vinyl alcohol), were purified and characterised with respect to their sizes, shapes and optical properties. Their inhibition potential on AChE and BChE was evaluated in vitro using an enzyme assay with o-nitrophenyl acetate or o-nitrophenyl butyrate as substrates, respectively. All three studied AgNPs were reversible inhibitors of ChEs. Among tested nanoparticles, Cl-AgNP was found to be the most potent inhibitor of both AChE and BChE. Although the detailed mechanism by which the AgNPs inhibit esterase activities remains unknown, structural perturbation of the enzyme may be the common mode of ChE inhibition by AgNPs.     

Potential protective effects of Spirulina platensis on liver,kidney, and brain acrylamide toxicity in rats

Environmental Science and Pollution Research - Acrylamide (AA) is a hazardous chemical that is widely used in industrial practices. Spirulina platensis (SP) is a blue green alga that is rich in...     

Clinical effects and cholinesterase activity changes in workers exposed to phorate (Thimet)

Abstract

Phorate (Thimet), an aliphatic derivative of phospnorus is a hignly toxic insecticide. In order to implement the safety measures, the clinical manifestations and cholinesterase (ChE) activity were evaluated before and after 2 weeks of exposure to this insecticide in 40 male tormulators.

The 2 week's exposure reveal signs and symptoms of toxicity in 60% of the formulators. Gastrointestinal symptoms and lowering of heart rate (bradycardia) were more prominent as compared to the neurological symptoms. A significant depression in plasma ChE activity was observed at the end of 1st week (55%) and 2nd week (71%) as compared to the respective pre‐exposure values. A recovery up to 79% of the pre‐exposure activity of this enzyme was noticed 10 days after cessation of the above exposure.     

Clinical effects and cholinesterase activity changes in workers exposed to Phorate (Thimet)

Phorate (Thimet), an aliphatic derivative of phosphorus is a highly toxic insecticide. In order to implement the safety measures, the clinical manifestations and cholinesterase (ChE) activity were evaluated before and after 2 weeks of exposure to this insecticide in 40 male formulators. The 2 week's exposure reveal signs and symptoms of toxicity in 60% of the formulators. Gastrointestinal symptoms and lowering of heart rate (bradycardia) were more prominent as compared to the neurological symptoms. A significant depression in plasma ChE activity was observed at the end of 1st week (55%) and 2nd week (71%) as compared to the respective pre-exposure values. A recovery up to 79% of the pre-exposure activity of this enzyme was noticed 10 days after cessation of the above exposure.     

Effects of selenium and mercury on the enzymatic activities and lipid peroxidation in brain, liver, and blood of rats

Recent studies have reported on the toxicity and related oxidative stress of selenium and mercury. The present study compares the effects of Se as sodium selenite (Na2SeO3) and Hg as mercuric chloride (HgCl2) separately and in combination. Rats received repeated oral doses of Se (0.5 micromol/ml), Hg (0.5 micromol/ml), or Se in combination with Hg (0.5 micromol/ml of each) for 5 consecutive days. Rat serum, brain and liver samples were collected for biochemical assays. The following biochemical alterations occurred in response to Hg treatment: protein content (brain and liver), acetylcholinesterase (AChE) (brain and serum), acid and alkaline (AcP and AlP) phosphatases (plasma and liver) and glutathione S-transferase (GST) (plasma and liver) activities were significantly (P<0.05) decreased, while lactate dehydrogenase (LDH) (plasma, brain and liver), aspartate and alanine aminotransferase (AST, ALT) (serum and liver) activities were significantly increased. Thiobarbituric acid reactive substances (TBARS) was significantly increased in brain and liver. Effect of Se alone included decreased AcP, AlP and GST (serum and liver) activities. However, LDH (serum, brain and liver) and AST (liver) and TBARS (brain and liver) increased. Selenium in combination with Hg partially or totally alleviated the toxic effects of Hg on different studied enzymes. It is concluded that Se could be able to antagonize the toxic effects of mercury.     

Temporal changes in the toxicity of pentachlorophenol to Chlorella pyrenidosa algae

The toxicity of pentachlorophenol (PCP) on Chlorella pyrenidosa algae was investigated with specific attention given to possible variation of toxic effects with time. A concentration-effect relationship was observed in which there was significant inhibition of PCP on cell density and chlorophyll A content. The inhibition rate of PCP on cell density was dependent on exposure time. The IC50 values after exposure times of 2, 4 and 6 days for cell growth were 4.18 +/- 0.49, 3.49 +/- 0.40 and 3.30 +/- 0.26 mg/L, respectively. There was also inhibition of chlorophyll A production, which appeared to increase marginally with exposure time for a given concentration of PCP. The corresponding IC50 values on day 2, 4 and 6 were 2.30 +/- 0.12, 2.63 +/- 0.38 and 3.30 +/- 0.34 mg/L, respectively. The effect of PCP on nitrate reductase (NR), was first stimulation followed by an inhibition phase. It is postulated that the observed temporal changes in the activity of nitrate reductase (NR) may occur through the addition or loss of phosphorus in the NR protein.     

Interconversions and toxicity changes in hexachlorocyclohexane isomers on dispersion in water

Abstract

Studies on the transformations of hexachlorocyclohexane isomers, α‐, β‐, γ‐ and δ‐, in aqueous solution were carried out at 25 ± 1°C over a period of four weeks. Gas liquid chromatographic technique was used for analysis. The results indicated a loss as well as interconversion of all the four isomers with time. The resulting changes in toxicity of the aqueous solution were studied against Drosophila using topical application. Toxicity studies with aqueous solution of technical hexachlorocyclohexane were simultaneously carried out for comparison. Toxicity of the aqueous solutions of α‐, β‐, and δ ‐isomers showed an increase while that of the γ‐isomer decreased significantly during the four week experimental period. Aqueous solution of technical HCH was equally toxic as that of the γ‐isomer initially and did not show much decrease in its toxicity at the end. Changes in toxicity of the individual isomer solutions were considered to be due, in part, to interconversions of HCH isomers.     

A two-generational reproductive toxicity study of zinc in rats

A two-generation reproductive toxicity study of zinc chloride (ZnCl(2)) was conducted in rats. F(o) male and female rats were administered 0.00 (control), 7.50 (low), 15.00 (mid) and 30.00 (high) mg/kg/day of ZnCl(2). Selected F(1) male and female rats were exposed to the same doses received by their parents (F(o)). Exposure of F(0) parental rats to ZnCl(2) showed significant reduction in fertility, viability (days 0 and 4), and the body weight of F(1) pups from the high-dose group but caused no effects on litter size, weaning index, and sex ratio. Similarly, the continued exposure of F(1) parental rats to ZnCl(2) also reduced fertility, liter size, viability (day 0), and the body weight of F(2) pups within the high-dose group but caused no effects on weaning index and sex ratio. Exposure of ZnCl(2) to F(0) and F(1) parental males resulted in a significant reduction in their body weights, and the F(0) and F(1) parental females did not show any significant difference in their body weights compared to their control groups. However, the postpartum dam weights of both F(0) and F(1) female rats were significantly reduced compared to their controls. Exposure of ZnCl(2) to F(o) and F(1) generation parental rats did not produce any significant change of their clinical signs as well as their clinical pathology parameters, except the alkaline phosphotase (ALK) level, which showed an upward trend in both sexes of both generations. Exposure of ZnCl(2) to F(0) rats resulted in a reduction of brain, liver, kidney, spleen and seminal vesicles weights of males and in the spleen and uterus of females. Similarly, exposure of F(1) rats to ZnCl(2) also resulted in reduction of brain, liver, kidney, adrenal, spleen, prostate and seminal vesicles weights of males and in spleen and uterus of females. ZnCl(2) exposure resulted in grossly observed gastro-intestianla (GI) tract, lymphoreticular/hematopoietic, and reproductive tract lesions in parental rats in both generations. Reduced body fat was also recorded in F(1) parental rats.     

A two-generational reproductive toxicity study of zinc in rats

A two-generation reproductive toxicity study of zinc chloride (ZnCl₂) was conducted in rats. F_o male and female rats were administered 0.00 (control), 7.50 (low), 15.00 (mid) and 30.00 (high) mg/kg/day of ZnCl₂. Selected F₁ male and female rats were exposed to the same doses received by their parents (F_o). Exposure of F₀ parental rats to ZnCl₂ showed significant reduction in fertility, viability (days 0 and 4), and the body weight of F₁ pups from the high-dose group but caused no effects on litter size, weaning index, and sex ratio. Similarly, the continued exposure of F₁ parental rats to ZnCl₂ also reduced fertility, liter size, viability (day 0), and the body weight of F₂ pups within the high-dose group but caused no effects on weaning index and sex ratio. Exposure of ZnCl₂ to F₀ and F₁ parental males resulted in a significant reduction in their body weights, and the F₀ and F₁ parental females did not show any significant difference in their body weights compared to their control groups. However, the postpartum dam weights of both F₀ and F₁ female rats were significantly reduced compared to their controls. Exposure of ZnCl₂ to F_o and F₁ generation parental rats did not produce any significant change of their clinical signs as well as their clinical pathology parameters, except the alkaline phosphotase (ALK) level, which showed an upward trend in both sexes of both generations. Exposure of ZnCl₂ to F₀ rats resulted in a reduction of brain, liver, kidney, spleen and seminal vesicles weights of males and in the spleen and uterus of females. Similarly, exposure of F₁ rats to ZnCl₂ also resulted in reduction of brain, liver, kidney, adrenal, spleen, prostate and seminal vesicles weights of males and in spleen and uterus of females. ZnCl₂ exposure resulted in grossly observed gastro-intestianla (GI) tract, lymphoreticular/hematopoietic, and reproductive tract lesions in parental rats in both generations. Reduced body fat was also recorded in F₁ parental rats.     

Protective effects of thymoquinone and diallyl sulphide against malathion-induced toxicity in rats

Environmental Science and Pollution Research - Malathion is a potent organophosphate insecticide that inhibits acetylcholinesterase (AChE) enzyme. Our experimental objective was to investigate the...     

Phosphorus availability changes chromium toxicity in the freshwater alga Chlorella vulgaris

Chromium (Cr) is one of the most serious pollutants in aquatic systems. This study examined the relationship between the toxic effects of Cr on the freshwater alga Chlorella vulgaris and phosphorus (P) availability on the algal physiology and ultrastructure. Cr inhibited C. vulgaris growth in a concentration- and time-dependent manner, and its inhibitory effect was related to the P concentration. In a low-P medium, Cr showed approximately 2.2–3.7-fold stronger toxicity than in a high-P medium. Cr was absorbed into the algal body where it disrupted the chloroplast structure and decreased the chlorophyll content. However, Cr had a weaker chlorophyll inhibitory ability and destructive power against the chloroplasts in the high-P medium than in the low-P medium due to the partial blockage of Cr absorption in high P-medium. Cr exposure also changed the metal ion and anion absorption profiles, which was also closely related to the concentration of P. Cr treatment increased the volume of the vacuole, and the larger vacuole reduced the space available for chloroplasts, as based on optical and electron microscopy results, but a higher P availability could alleviate this damage. These results suggest that high P alleviated the toxicity of Cr by decreasing Cr absorption and increasing the absorption of beneficial ions. It is, therefore, necessary to consider the phosphorus availability when the toxicity of metal compounds is evaluated.     

Effect of quinalphos on blood enzymes and its acute toxicity in bubalus bubalis

Abstract

The acute toxic effects of quinalphos (0,0‐diethyl 0–2‐quinoxalyl phosphorothioata) uere investigated in male buffalo calves. Quinalphos was administered in single oral doses of 5, 7.5, 8.5 and 10 mg/kg body wt. and its effects on erythrocyte and plasma cholinesterases, serum aspartate aminotransferase and blood glucose were studied at various time intervals. The lowest dose (5 mg/kg) produced no apparent toxic symptoms. All the animals given highest dose (10 mg/kg) died within 60–82 hours after dosing. Quinalphos at all the dose levels markedly inhibited the erythrocyte and plasma cholinesterases (68–100%) and significantly elevated the levels of serum aspartate aminotransferase and blood glucose. Seven days after the administration of quinalphos, the blood cholinesterases in survivors remained inhibited to the extent of 41–77% whereas the levels of serum aspartate aminotransferase and blood glucose were comparable to control values.     

Effect of coumaphos on cholinesterase activity, hematology, and biochemical blood parameters of bovines in tropical regions of Mexico

To assess the effect of coumaphos [O-(3-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-yl) O,O-diethyl phosphorothioate] exposure on physiological responses during bovine production, acetylcolinesterase (AChE) and butyrylcholinesterase (BuChE) activities were measured in whole blood, erythrocytes, and plasma of healthy male steers (Bos Taurus x Bos indicus) sprayed with coumaphos at a non-lethal dose of 1 mg kg(- 1) body weight per day once every 14 (in vivo group) or 21 days (southern and central groups). Coumaphos topically administered at 1 mg/kg body weight per day to cattle under normal management practices in tropical areas produced a significant inhibition in erythrocyte (RBC) AChE and BuAChE activities when compared to baseline levels. RBC-AChE activity for the in vivo group decreased 71.3% (P < 0.05) and BuChE activity 59.1% (P < 0.05); RBC-AChE activity decreased 55.1% (P < 0.05) (southern group) and 43.4% (P < 0.05) (central group). Compared to the control specimens, steers from in vivo, southern, and central groups after 150 days of exposure had lower (P < 0.05) leukocyte count, absolute lymphocyte, erythrocyte, and platelet counts. Decreases in RBC-AChE activities correlated with decreased lymphocyte (r = 1.000, p = 0.01), erythrocyte (r = 1.000, p = 0.003), and platelet counts (r = 0.841, p = 0.036). Significantly increased BUN levels (P < 0.05) correlated with the decrease in RBC-AChE activities (r = - 0.997, p = 0.047) and with the decrease in absolute red blood cell (r = - 0.883, p = 0.020) and lymphocyte (r = - 0.825, p = 0.043) counts; increased (P < 0.05) total plasma protein levels correlated with the decrease in RBC-AChE activities (r = -0.998, p = 0.043), absolute red blood cell (r = - 0.998, p = 0.040), lymphocyte (r = - 0.893, p = 0.017), and platelet (r = -0.855, p = 0.030) counts. The physiological responses correlated with the erythrocyte acetylcholinesterase inhibition could be considered as early indicators or warning responses of bovine exposures to organophosphorus pesticides (OPs).     

Effect of coumaphos on cholinesterase activity,hematology, and biochemical blood parameters of bovines in tropical regions of Mexico

To assess the effect of coumaphos [O-(3-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-yl) O,O-diethyl phosphorothioate] exposure on physiological responses during bovine production, acetylcolinesterase (AChE) and butyrylcholinesterase (BuChE) activities were measured in whole blood, erythrocytes, and plasma of healthy male steers (Bos Taurus x Bos indicus) sprayed with coumaphos at a non-lethal dose of 1 mg kg^{? 1} body weight per day once every 14 (in vivo group) or 21 days (southern and central groups). Coumaphos topically administered at 1 mg/kg body weight per day to cattle under normal management practices in tropical areas produced a significant inhibition in erythrocyte (RBC) AChE and BuAChE activities when compared to baseline levels. RBC-AChE activity for the in vivo group decreased 71.3% (P < 0.05) and BuChE activity 59.1% (P < 0.05); RBC-AChE activity decreased 55.1% (P < 0.05) (southern group) and 43.4% (P < 0.05) (central group). Compared to the control specimens, steers from in vivo, southern, and central groups after 150 days of exposure had lower (P < 0.05) leukocyte count, absolute lymphocyte, erythrocyte, and platelet counts. Decreases in RBC-AChE activities correlated with decreased lymphocyte (r = 1.000, p = 0.01), erythrocyte (r = 1.000, p = 0.003), and platelet counts (r = 0.841, p = 0.036). Significantly increased BUN levels (P < 0.05) correlated with the decrease in RBC-AChE activities (r = ? 0.997, p = 0.047) and with the decrease in absolute red blood cell (r = ? 0.883, p = 0.020) and lymphocyte (r = ? 0.825, p = 0.043) counts; increased (P < 0.05) total plasma protein levels correlated with the decrease in RBC-AChE activities (r = ?0.998, p = 0.043), absolute red blood cell (r = ? 0.998, p = 0.040), lymphocyte (r = ? 0.893, p = 0.017), and platelet (r = -0.855, p = 0.030) counts. The physiological responses correlated with the erythrocyte acetylcholinesterase inhibition could be considered as early indicators or warning responses of bovine exposures to organophosphorus pesticides (OPs).     

Effect of the trichothecene deoxynivalenol on brain biogenic monoamines concentrations in rats and chickens

Male Sprague-Dawley rats (180 g) and 28-day-old Single Comb White Leghorn Cockerels (300 g) were orally dosed with deoxynivalenol (DON) at 2.5 mg kg-1 body weight. In the first experiment, whole brains were collected at 2, 6, 12, 24 and 48 hours after the toxin treatment and analyzed for brain biogenic monoamines by high-performance liquid chromatography with electrochemical detection. Although several interesting trends were observed, DON did not influence whole brain concentrations of monoamine neurotransmitters or their metabolites in either species, at any time. In a second experiment, brains were collected 24 hours postdosing, dissected into 5 brain regions (pons and medulla oblongata, cerebellum, hypothalamus, hippocampus and cerebral cortex), and analyzed. DON treatment resulted in significantly elevated concentrations of serotonin (HT) and 5-hydroxyindole-3-acetic acid (HIAA) in all brain regions of the rat. However, this was not seen in poultry, where DON treatment resulted in a decrease in norepinephrine (NE) in the hypothalamus and hippocampus, and a decrease in dopamine (DA) in the pons and medulla oblongata region. These results suggest that DON influences brain biogenic amine metabolism, and that there may be intraspecies differences in the central effects of this mycotoxin.     

Studies on oxygen toxicity after simultaneous administration of paraquat and chelate-forming agents in rats

The influence of intravenously administered mixtures of paraquat and the chelating agents CaNa₂-EDTA or dithiocarb on the toxicity of oxygen at normal pressure was studied in rats. No increase in toxic effects of the combination paraquat-oxygen was seen by additionally administered chelate-forming agents.This paper completes the investigations on oxygen toxicity after administration of various chelate-forming agents in mice¹.     

Studies on thallium toxicity, its tissue distribution and histopathological effects in rats

The distribution of thallium (Tl) in the body and its toxic effect on the histology and function of the liver and kidney of rats after Tl administration were investigated using biochemical and histopathological assays. Male albino rats exhibited a markedly dose-dependent increase in the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at 16 h after an intraperitoneal injection of 30, 60 or 120 mg/kg Tl. The serum level of creatinine in the rats injected with 30 mg/kg Tl, elevated significantly after 4 days of administration. The distribution of Tl in the tissues of intoxicated rats was uneven. The content of Tl was found to be highest in the kidney, followed by ileum, stomach and liver. Histological examination demonstrated frequent occurrence of hepatocyte necrosis and vacuolation in the liver and pathological changes of renal tubules in the treated rats.     

Ameliorative effects of corn silk extract on acetaminophen-induced renal toxicity in rats

Environmental Science and Pollution Research - The current study aimed to investigate the protective effect of corn silk methanolic extract (CSME) against acetaminophen (APAP)-induced...     

Bioavailability and toxicity to rats of bound residues of 14C-pirimiphos-methyl in stored wheat.

Wheat grains were treated with 14C-pirimiphos-methyl to generate bound residues for testing their bioavailability to rats. Bound residues accounted for 25% of the applied dose (50 ppm) at the end of one year. When the grain bound residues were fed to rats for 48 hours the animals eliminated 30 and 40% of the administered dose in urine and feces respectively, after 5 days. Radioactivity in some selected organs and blood accounted for 37% of the administered dose after 2 days, which gradually declined to 1% after 5 days. These data indicate that wheat-bound pirimiphos-methyl residues are moderately bioavailable to rats. In a 90-day feeding study, inhibition of plasma cholinesterase and brain acetylcholinesterase strongly suggest that the bound residues possess a toxicological potential.