Malathion alters biochemical parameters of liver in albino rats

Liver represents a key role in the physiology of animals as most of the metabolic mechanisms occur in it. The pesticides entered into the human body through various routes viz., oral, dermal, inhalation, etc. affect the liver and alter the metabolic rate of the individual. Malathion is an organophosphate pesticide, commonly used in all kinds of crops to protect them from different kinds of pests. Here, we studied the toxicological effects of malathion on the liver of albino rats. Different doses of malathion @ 25, 50, 75 and 100 mg/ kg body wt. were orally administered to the rats for 7 and 15 days. The selected biochemical parameters such as protein, sugar, alkaline phosphatase, acid phosphatase, glutamyl oxalotransaminase (GOT), glutamyl pyruvate transaminase (GPT) and glucose-6- phosphatase dehydrogenase (G6PD) values were measured. Results indicates that the value of protein, acid phosphatase and GPT significantly increases as 5.54+0.99 to 7.35+0.48 mg/g, 14.5+2.50 to 27.37+6.43 mol/g/h and 28.52+3.62 to 37.87+3.94 IU/dL, respectively after treatment. But the sugar, alkaline phosphatase and G6PD value significantly decreases after treatment from 126.12+2.64 to 84.5+10.83mg/g, 29.12+2.64 to 15.5+4.24,6.46 +1.56 mol/g/h to 4.62+1.18 IU/gHb, respectively. Value of GOT increased moderately from 38.5+2.44 to44.87+3.31 IU/dL. The above changes revealed the toxic effects of the pesticide malathion.

A highly sensitive bio-barcode immunoassay for multi-residue detection of organophosphate pesticides based on fluorescence anti-quenching / 药物分析学报

Balancing the risks and benefits of organophosphate pesticides(OPs)on human and environmental health relies partly on their accurate measurement.A highly sensitive fluorescence anti-quenching multi-residue bio-barcode immunoassay was developed to detect OPs(triazophos,parathion,and chlorpyrifos)in apples,turnips,cabbages,and rice.Gold nanoparticles were functionalized with monoclonal antibodies against the tested OPs.DNA oligonucleotides were complementarily hybridized with an RNA fluorescent label for signal amplification.The detection signals were generated by DNA-RNA hybridization and ribonuclease H dissociation of the fluorophore.The resulting fluorescence signal en-ables multiplexed quantification of triazophos,parathion,and chlorpyrifos residues over the concen-tration range of 0.01-25,0.01-50,and 0.1-50 ng/mL with limits of detection of 0.014,0.011,and 0.126 ng/mL,respectively.The mean recovery ranged between 80.3％and 110.8％with relative standard deviations of 7.3％-17.6％,which correlate well with results obtained by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The proposed bio-barcode immunoassay is stable,reproducible and reliable,and is able to detect low residual levels of multi-residue OPs in agricultural products.

Association between exposure to organophosphate pesticides and levels of oxidative stress in pregnant women with different paraoxonase 1 genotypes / 上海交通大学学报（医学版）

Objective: To investigate whether paraoxonase 1 (PON1) genotypes were effect modifiers in the relationship between exposure to organophosphate pesticides (OPs) and oxidative stress level in pregnant women. Methods: A total of 204 pregnant women recruited from a hospital in Shandong Province were included in the study. Four nonspecific dialkyl phosphate (DAP) metabolites of OPs were measured in each urine sample. Levels of two oxidative stress biomarkers [total free sulfhydryl (-SH) and malondialdehyde (MDA)] were measured in serum samples. Blood samples were also analyzed for detecting PON1 genotypes (PON1-108, PON1192 and PON155). Separate linear regression models were conducted to explore the relationship between DAP metabolite levels and oxidative stress levels in all 204 pregnant women or women within each PON1 genotype. Results: There was no significant association between DAP metabolite levels and oxidative stress levels in all 204 women. Levels of dimethyl phosphates [β (95% CI): -104.10 (-191.31, -16.88)] and dialkyl phosphates [β (95% CI): -111.78 (-221.84, -1.72)] were negatively associated with -SH level among pregnant women with PON1192RR genotype, but this association was not found among women with other genotypes. Conclusion: OP exposure may be associated with a higher oxidative stress level among pregnant women with PON1192RR genotype.

Association between exposure to organophosphate pesticides and levels of oxidative stress in pregnant women with different paraoxonase 1 genotypes / 上海交通大学学报（医学版）

Objective·To investigate whether paraoxonase 1 (PON1) genotypes were effect modifiers in the relationship between exposure to organophosphate pesticides (Ops) and oxidative stress level in pregnant women.Methods · A total of 204 pregnant women recruited from a hospital in Shandong Province were included in the study.Four nonspecific dialkyl phosphate (DAP) metabolites of Ops were measured in each urine sample.Levels of two oxidative stress biomarkers [total free sulfhydryl (-SH) and malondialdehyde (MDA)] were measured in serum samples.Blood samples were also analyzed for detecting PON1 genotypes (PONI-108,PON1192 and PON155).Separate linear regression models were conducted to explore the relationship between DAP metabolite levels and oxidative stress levels in all 204 pregnant women or women within each PON1 genotype.Results· There was no significant association between DAP metabolite levels and oxidative stress levels in all 204 women.Levels of dimethyl phosphates [β (95％ CI):-104.10 (-191.31,-16.88)] and dialkyl phosphates [f (95％ CI):-111.78 (-221.84,-1.72)] were negatively associated with-SH level among pregnant women with PON1192RR genotype,but this association was not found among women with other genotypes.Conclusion· OP exposure may be associated with a higher oxidative stress level among pregnant women with PONI192RR genotype.

Evaluación de la exposición a órganofosforados y carbamatos en trabajadores de una comunidad agraria / Exposure to organophosphates and carbamates in workers of an agricultural community

En Venezuela la utilización de organofosforados y carbamatos ha contribuido a generar un escenario propicio para la aparición de intoxicaciones agudas y crónicas a nivel de la población, transformándose esta situación en un problema de Salud Pública. Se analizó la exposición en trabajadores de una comunidad agraria de la Colonia Tovar, Estado Aragua. Estudio descriptivo-correlacional en trabajadores expuestos a plaguicidas. El Grupo Expuesto (GE) 17 trabajadores (58,8% del sexo masculino y 41,2%femenino), edad promedio de 37,06 ± 15,66 años y un Grupo Control (GC) con 13 trabajadores del personal administrativo de la Universidad de Carabobo (53,8% del sexo masculino y 46,2%femenino), edad promedio 39,77 ± 13,23 años. Se realizó una entrevista y se determinaron niveles de colinesterasa sérica y parámetros hematimétricos y bioquímicos. En el GE un valor promedio de la actividad de la colinesterasa de 6,7465 ± 1,0314 U/L y para el GC de 8,6546 ± 1,6014 U/L. Las medias de la actividad de la colinesterasa sérica se encontraron dentro de los parámetros considerados normales (4,970-13,977U/L) para ambos grupos. Se evidencia la existencia de diferencia estadísticamente significativa (p< 0,05) entre las medias para el biomarcador de efecto en estudio en el GE. La manipulación inadecuada de los plaguicidas y los síntomas asociados a manifestaciones clínicas debido a la exposición. Un 41,2% de los empleados utilizan medidas de protección personal. Los trabajadores expuestos a organofosforados y carbamatos presentaron biomarcadores de exposición y de efecto dentro de los rangos normales, con presencia de síntomas que pudieran relacionarse con dicha exposición.

In Venezuela, the use of organophosphates and carbamates has contributed to generate a suitable scenario for the appearance of acute and chronic poisoning in the population, turning this situation into a Public Health problem. The exposure in an agrarian worker community from La Colonia Tovar - Aragua State was analyzed. This is a descriptive-correlational study in workers exposed to pesticides. The exposed group, (EG) 17 workers (58.8% male and 41.2% female), mean age 37.06 ± 15.66 years old, and a control group (CG) with 13 administrative staff from University of Carabobo (53.8% male and 46.2% female), mean age 39.77 ± 13.23 years old. An interview was conducted and serum cholinesterase levels were determined; and even, hematimetric and biochemical parameters. In the EG an average value of the cholinesterase activity was 6,7465 ± 1,0314 U/L, and for the CG 8,6546 ± 1,6014 U/L. The means of serum cholinesterase activity were normal (4,970 - 13,977 U/L) for both groups. It is evident the existence of statistically significant difference (p<0.05) between the means for the effect biomarker under study in the EG. The inappropriate handling of pesticides and symptoms associated with clinical manifestations due to exposure. 41.2% of the employees use personal protection measures. Workers exposed to organophosphates and carbamates presented biomarkers of exposure and effect within normal ranges, with the presence of symptoms related to this exposur.

The synergetic effect of combined astaxanthin and lithium chloride treatment on cognitive dysfunc-tion of chronic omethoate poisoned mice / 中华行为医学与脑科学杂志

Objective To investigate the synergetic effect of combined astaxanthin ( AST) and lith-ium chloride ( LiCl) treatment on cognitive dysfunction of chronic omethoate poisoned mice. Methods 8 mice were selected randomly as control group from 55 healthy adult male Kunming mice,and the rest were used to establish chronic organophosphate poisoning cognitive impairment models by injecting omethoate 5 mg/kg subcutaneously every day for 4 weeks. Totally 40 successfully established models were randomly divid-ed into model group,AST group,edaravone group,LiCl group and AST+LiCl group with 8 in each. Morris wa-ter maze test was used to examine the learning and memory ability of mice. Contents of reactive oxygen spe-cies (ROS) in hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). Activity of superoxide dismutase ( SOD) in hippocampus was measured by colorimetric assay. Morphology of hippocam-pus area was observed by HE staining. The distribution and expression of p-PI3K,p-Akt,p-GSK3β and p-CREB were determined by immunohistochemical staining ( IHC staining) and Western blot. Results The average escape latency of 5 days in each group was statistically significant (F=1662.147, P<0.05) . The av-erage escape latency of 5 days in AST+LiCl group was significantly lower than that in model group ( all P<0.05) and was lower than other treatment groups. Compared with the control group (0.087±0.007,0.084± 0.009,0.097±0.002,0.076±0.012),the hippocampal neuronal injury in model group was serious,the expres-sions of p-PI3K (0.032±0.008),p-Akt (0.03±0.006),p-GSK3β (0.028±0.007) and p-CREB (0.020± 0.008) was significantly lower ( all P<0.05) . The injuries of hippocampal neurons in AST+LiCl group were slightly lighter than that in model group,and the expression of p-PI3K (0.067±0.008),p-Akt (0.065± 0.005),p-GSK3β (0.068±0.009) and p-CREB (0.062±0.008) in hippocampus was significantly higher than that in model group ( all P<0.05) . Conclusion Combined AST and LiCL treatment exerts neuroprotec-tive effect on cognitive dysfunction induced by chronic organophosphate poisoning via up-regulating the ex-pression of Akt/GSK3β/CREB.

Inhibición de butirilcolinesterasa por exposición a malatión: efectos sobre nocicepción y motricidad en ratas / Inhibition of butyrylcholinesterase induced by exposition to Malathion: effects on nociceptive and motor behavior in rats

Dada la presencia colinérgica en el sistema nociceptivo y la frecuente exposición al malatión, plaguicida organofosforado inhibidor de la Acetilcolinesterasa, se evaluó el impacto del aumento en el tono colinérgico inducido por la exposición a dosis bajas de malatión sobre la conducta nociceptiva y motora en ratas. Se estudiaron 20 ratas Sprague Dawley, machos (350-400g); en un grupo control (n=10) se inyectó 1mL NaCl 0,9% diario (i.p.) y a un grupo experimental (n=10) se inyectó 1mL de malatión (40mg.Kg-1.dia-1, en NaCl 0,9%, i.p) diario por 7 días. Se evaluó el primero, cuarto y séptimo día de tratamiento, el umbral nociceptivo (tiempo de reacción en la plancha caliente a 50ºC), la motricidad (distancia recorrida en 5 minutos) como evaluador de respuesta motora, y la actividad de la Butirilcolinesterasa plasmática (BuChE) como un marcador de actividad colinérgica. La actividad BuChE disminuyó progresivamente en 23,6%; 48,9% y 53,2%, el primero, cuarto y séptimo día, respectivamente, mostrando una cinética inhibitoria del tipo logarítmica: % Inhibición BuChE = 53,73 x (1+1,22-0,81xdía); r=0,93; P<0,05. Las dosis utilizadas corresponden a un nivel de exposición no letal con el fin de lograr cronicidad. La motricidad fue similar en ambos grupos (controles: 108,5 ± 30,1; malatión: 102,1 ± 43,9 cm; P>0,05; X ± DE) al igual que el umbral nociceptivo (controles:13,5 ± 5,4; malatión 15,2 ± 6,5s; P>0,05). Los datos obtenidos muestran que a pesar de la intensa inhibición de la BuChE inducida por bajas dosis de malatión, la participación funcional colinérgica en el proceso de la nocicepción es muy reducida o marginal, lo cual sugiere el predominio de otros neurotransmisores en el procesamiento nociceptivo espinal y supraespinal.

Due to cholinergic presence in the nociceptive system and the frequent exposition to Malathion, an organophosphorated pesticide with an Achetylcholinesterase inhibitory effect, the impact of the increased cholinergic tone induced by a low dose of malathion on the nociceptive and motor behavior of rats was tested. Male Sprague Dawley rats (350-400g) were divided into two groups: Control (n=10) injected with 1mL NaCl 0.9% daily (i.p.) and Malathion (n=10) injected with 1mL of malathion (40 mg.Kg-1.day-1, in NaCl 0.9%, i.p) daily for 7 days. At days 1, 4 and 7 of treatment the nociceptive threshold was evaluated by the hot-plate method at 50ºC, motor activity by total rat displacement in 5 min, and the plasmatic Butyrylcholinesterase (BuChE) activity as a cholinergic biomarker. BuChE activity progressively decreased by 23.6%; 48.9% and 53.2% at days 1, 4 and 7 of treatment, respectively, showing a logarithmic inhibitory kinetics: % of BuChE inhibition= 53.73 x (1+1,22-0,81xday); r=0,93; P<0,05. The tested exposition dose was non-lethal in order to simulate chronic toxicity. Despite the BuChE inhibition, no statistical differences between both groups were found, neither for the nociceptive threshold (Controls:13.5±5,4; Malathion 15.2±6.5s; P>0.05; Mean±SD) nor for motor activity (Controls:108.5±30,1; malathion:102.1±43.9cm; P>0.05). These results strongly suggest that despite the intense BuChE inhibition induced by exposition to a low dose of malathion, the contribution of the cholinergic system in nociception is reduced or even marginal, which reveals the action of other neurotransmitters in this process.

Investigation on the treatment opportunity of mechanical ventilation for acute severe organophosphorus pesticide poisoning patients with respiratory failure / 中国基层医药

Objective To explore the treatment opportunity of mechanical ventilation for acute severe organophosphorus pesticide poisoning patients with respiratory failure.Methods According to the different indications of mechanical ventilation,115 acute severe organophosphorus pesticide poisoning patients with respiratory failure were divided into the observation group A (40 cases),the observation group B(38 cases)and the control group(37 cases).The cure rate,aspiration pneumonia incidence,duration of mechanical ventilation,length of hospital stay of the three groups were analyzed.Results The cure rate of the observation group A(97.5％) was significantly higher than that of the control group(83.4％)and the observation group B (92.1％) (P ＜ 0.05 or P ＜ 0.01) ;The aspiration pneumonia of the observation group(2 cases) was significantly less than that of the control group(8 cases)(P ＜ 0.05) ;The hospitalization time [(4.46 ± 0.51) d,(7.11 ± 0.83) d] and the duration of mechanical ventilation [(55.40 ± 5.24)h,(79.47 ± 2.44) h] of the observation group A and the observation group B were significantly shorter than those of the control group [(10.40 ± 1.12) d,(100.30 ± 2.15) h] (all P ＜ 0.01) ; The hospitalization time and the duration of mechanical ventilation of the observation group A [(4.46 ± 0.51) d,(55.40 ± 5.24) h] were significantly shorter than those of the observation group B [(7.11 ± 0.83)d,(79.47 ± 2.44)h] (all P ＜ 0.01).Conclusion Respiratory rate ≥30 times/min and ＜ 34 times/min or ≤ 10 times/min,or spontaneous breathing weakened,and blood gas analysis prompted hypoxemia(60 mm Hg ＜ PaO2 ≤ 70 mm Hg)is best opportunity of mechanical ventilation for acute severe organophosphorus pesticide poisoning patients with respiratory failure.

Exposición a organofosforados y desempeño cognitivo en escolares rurales chilenos: un estudio exploratorio / Exposure to organophosphate and cognitive performance in chilean rural school children: an exploratory study

OBJETIVO: evaluar la presencia de metabolitos organofosforados en la orina de escolares rurales y estimar la asociación con el desempeño cognitivo. METODOLOGIA: estudio exploratorio de diseño transversal. Se midió en 25 niños el funcionamiento cognitivo con el test de inteligencia WISC-III y concentraciones de metabolitos organofosforados en orina. RESULTADOS: 56% de los niños presentaron concentraciones sobre el límite de detección para el dimetilfosfato (DMP) y el dimetiltiofosfato (dmtp), y 92% presentó el metabolito dietilfosfato (dep) sobre este límite. En el WISC-III,el coeficiente intelectual (ci) bajo el promedio (CI > 90) corresponde a: CI total = 60%; CIejecución = 64%; CIverbal = 52%; CI organización perceptual = 60%; CIvelocidad de procesamiento = 95%; y CI ausencia de distractibilidad = 64%. Se encontró una asociación inversa entre el factor velocidad de procesamiento y el dmtp (rs = -0,44, p = 0,014). CONCLUSIONES: los resultados indican exposición a plaguicidas organofosforados en escolares rurales medidos con biomarcadores de metabolitos organofosforados en orina. Se observó relación entre la presencia de un metabolito organofosforado y un factor de desempeño cognitivo de la prueba WISC-III. Se considera pertinente evaluar los efectos de la presencia de metabolitos organofosforados en el funcionamiento cognitivo en una muestra mayor, considerando otras variables de exposición.

OBJECTIVE: to evaluate the presence of organophosphate metabolites (OP) in the urine of rural schoolchildren and estimate its association with their cognitive performance. METHODOLOGY: a cross-sectional exploratory study in which a total of 25 children were assessed. Cognitive functioning was measured using the WISC-III intelligence test. Additionally, the concentration of OP metabolites in their urine was tested. RESULTS: 56% of the children had concentration levels above the detection limit for dimethylphosphate (DMP) and dimethyltiophosphate (DMTP). Moreover, 92% of them had the metabolite diethylphosphate (DEP) values on this limit. Regarding the WISC-III, the intelligence quotient (IQ) values below the average (IQ > 90) correspond to: Total IQ = 60% performance IQ = 64%, verbal IQ = 52%, perceptual organization IQ = 60%, processing speed IQ = 95%, and freedom from distractibility IQ = 64%. An inverse association was found between the processing speed factor and DMTP (r s = -0.44, p = 0.014). CONCLUSIONS: results indicate that the rural schoolchildren whose urine was measured with OP metabolite biomarkers had been exposed to OP pesticides. A relationship was observed between the presence of OP metabolites and the cognitive performance factor of the WISC-III test. We believe it is appropriate to evaluate the effects of the presence of OP metabolites on cognitive functioning in a larger sample, while considering other exposure variables.

Development of an automated method for the determination of human paraoxonase1 activity.

Background: Human plasma paraoxonase1 (PON1) is an esterase catalyzing the hydrolysis of organophosphorus pesticides and other xenobiotics. The aims of this study were to develop a rapid method to determinate PON1 activity, evaluate some interference, and study the influence of storage temperature on PON1 activity assay. Methods: Measurement of PON1 activity was performed for 369 samples by measuring the hydrolysis of paraoxon using a spectrophotometric method adapted on konelab 30 . Results: The developed method facilitates the determination of PON1 activity at the rate of more than 200 samples per hour, and it is linear between 2 and 900 IU/L. Intra and inter-assay imprecision coefficients of variation were 2% and 5% respectively. PON1 activity in serum was correlated with those in heparinized plasma (r = 0.994, p < 0.001) and in plasma/EDTA (r = 0.962, p < 0.001). The mean inhibition of the PON1 activity was, by EDTA/K3, 41 ± 10 %. There was not significant PON1 activity variation after 40 days of storage at -20°C or at +4 C. There were no substantial interferences from haemoglobin, jaundice and hyperlipidemia. Conclusion: The developed method is reliable, reproducible, and suitable. It can also be performed on heparinized plasma for the determination of PON1 activity. Hence, it may be useful for assaying PON1 activity in several intoxications such as organophosphorus, sarin, and soman nerve agents.

Assessment of chlorpyrifos toxicity on certain organs in rat, Rattus norvegicus.

Chlorpyrifos, an organophosphate insecticide of phosphorothioate group was orally administered to male rats at the doses of 3, 6 and 9 mg kg-1d-1 for 90 days. Animals exposed to high dose (9 mg kg-1d-1) showed signs of toxicity including piloerection, diarrhoea, nose and eye bleeding, reduced body weight and death of animals. Organ weight ratio of different vital organs did not show any change except increase in adrenal weight and decrease in the weight of testes in animals of high dose (9 mg kg-1d-1). A dose dependent inhibition of acetylcholinesterase (AChE) activity in RBC (22-60%) and brain (7-52%) was observed. Microscopic examination of different tissues of male rats showed minor histopathological changes in brain, liver, testis, epididymis and adrenal. The activity of testicular enzymes SDH, G-6-PDH and testicular content of sialic acid and cholesterol were found increased in animals of high dose (9 mg kg-1d-1). There was decrease in RBC counts and levels of hemoglobin (Hb) and hematocrit (HCT) with increase in WBC counts. While, total protein was decreased significantly at all the dose levels in testes and epididymis, glucose level showed a significant decrease at high dose. A dose dependent increase was observed in the level of serum triglycerides. There was no change in sperm motility and sperm morphology at any dose level except a decrease in sperm counts (114.1x 106 g-1 in high dose for group against 158.9 x 106 g-1 controls). It is suggested that chlorpyrifos at 9mg/kg/d dose for 90 days has caused toxicological changes along with mild testicular and spermatotoxic effects in male rats.

Consumption of Pesticide and its Health Impact / Монголын Анагаах Ухаан

Even though the use and production of polychlorinated biphyls (PCBs) and organochlorine (OC) pesticides have been regulated worldwide, in agreement with the Stockholm convention in 2001, they are still posing serious environmental threat both to wildlife and humans. These lipophilic compounds, with high resistance to degradation and long half- lives in humans, have been confirmed to bioaccumulate in fatty tissues of biological specimens such as blood, breast milk, and adipose tissues through dietary intake. The analysis of these tissues reveals the rate of exposure and distribution in the environment.