Adverse effects of organophosphorus pesticides on the liver: a brief summary of four decades of research

Hou Y., Liu S., Wang L., Wu S.

Acute organophosphorus pesticides poisoning has a serious threat on people's health. This study aimed to investigate the pathogenesis and molecular mechanism of multiple organ dysfunction syndrome (MODS) in severely monocrotophos-poisoned rabbits.Chinchilla rabbits were used to build the monocrotophos-poisoned animal model via subcutaneous abdominal injection. Acetylcholinesterase activity was determined using the dithiobisnitrobenzoic acid enzyme kinetics method, and the free organophosphorus (FOP) toxic substances content was analyzed using the enzyme inhibition method. The contents of tumor necrosis factor (TNF-α), interleukin 1-β (IL-β) and thromboxane B2 (TXB2) in the plasma and tissue homogenates were determined via radioimmunoassay.Twenty-four hours after exposure, in comparison to the plasma, blood cells and homogenates of various tissues, the bile had a significantly different FOP content (P < 0.05). In different phases, HE staining results confirmed that several degrees of pathological lesions (such as hemorrhage, edema, degeneration and necrosis) were detected in FOP poisoned rabbits. The TXB2 and TNF contents in plasma were significantly higher than those of the control (P < 0.05). Except for the intercostal muscle, all of the tissues had significantly higher TXB2 contents than the control. The TNF contents of the liver and lung and the IL-1β contents of the liver and kidney were significantly higher than those of the control (P < 0.05).FOP stored in the gallbladder may play important role in enterohepatic circulation. In MODS rabbits, caused by OP poisoning, the TXB2 and TNF-α may play important role in inflammatory response and complement and coagulation systems respectively.

Yazdinezhad A., Abbasian M., Hojjat Hosseini S., Naserzadeh P., Agh-Atabay A., Hosseini M.

Chlorpyrifos (CPF) is one of the most widely used organophosphorus, which has spurred renewed interest. This study was conducted to investigate the protective effect of ziziphora tenuior extract against CPF-induced liver and lung toxicity. This study conducted 8-week rat sub-chronic toxicity study and then the effect of ziziphora tenuior extract in 3 different doses (40, 80, 160 mg/kg) was determined. We administrated maximum tolerated dose of CPF (6.75 mg/kg) by gavage for 8 weeks (5 times in week) to male rats. Rats were sacrificed 24 h after last dose and the biochemical analysis, which confirms involvement of oxidative stress in the pathogenesis of CPF toxicity in liver including increased in lipid peroxidation, protein carbonyl content, and ROS formation, glutathione depletion, decreased of antioxidant effect via frap oxidation and cytochrome c expulsion. In addition, pathological lesions confirm the dysfunction of the organs (liver and lung). In addition, using of ziziphora extract as an antioxidant is resulted in amelioration of oxidative stress marker in liver and lung damage. In conclusion, the current study revealed that CPF toxicity is related to oxidative stress and induction of cell death signaling and cotreatment with ziziphora extract is recommended in the routine therapy for the protection against CPF induced liver and lung tissue damage.

Li B., Ma Y., Zhang Y.H.

Trichlorfon is an organophosphate insecticide that is widely used in aquaculture and agriculture against parasitic infestations and has caused aquatic toxicity to non-target organisms. To evaluate the effects of low doses of trichlorfon on the oxidative stress and hepatotoxicity in amphibians, Chinese brown frogs (Rana chensinensis) were exposed to trichlorfon at concentrations of 0, 0.01, 0.1, and 1.0 mg/L for 2 and 4 weeks. Then, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and the content of malondialdehyde (MDA) in hepatic tissue were examined to evaluate the effects of oxidative stress and lipid peroxidation. The histopathological alternations to the liver were observed through light and transmission electron microscopy (TEM). The results showed that SOD and CAT activities were increased in the livers of frogs exposed to various concentrations of trichlorfon. The GST activity showed no significant changes at any concentration after 2 weeks of exposure, whereas there was an initial increase after exposure to 0.1 mg/L of trichlorfon at 4 weeks. The content of MDA revealed a significant decrease after exposure. Histopathological and ultrastructural studies showed that trichlorfon induced hyalinization, vacuolation, nucleus necrosis, and cellular swelling in hepatocytes. These results suggest that low doses of trichlorfon could induce oxidative stress, lipid peroxidation, and hepatic lesions in frogs, which shows that even lower, non-lethal doses of trichlorfon are potentially toxic to amphibians.

Ahmadipour A., Sharififar F., Pournamdari M., Bamkan A.M., Hosseini A., Afrapoli F.M., Karami-Mohajeri S.

This study was aimed to evaluate the protective effects of methanolic extract of Zataria Multiflora Boiss (Z. multiflora) against oxidative stress induced by malathion (MT) in male Wistar rats in comparison to N-acetylcysteine (NAC). Rats were randomly divided into 6 groups (n: 8) and treated daily for 28 days. They received MT (150 mg/kg), Z. multiflora methanolic extract (50, 100, and 200 mg/kg), and NAC (200 mg/kg) alone or in combination. This study included a histopathological examination of liver tissue in parallel with measurement of serum aminotransferases. Activities of antioxidant enzymes, total glutathione (GSH), and lipid peroxidation end products in plasma and tissue were also measured. Subacute exposure of rats to MT resulted in a significant morphological change in tissue, an increase in plasma aminotransferases, and oxidative damage. Both NAC and Z. multiflora at the dose of 200 mg/kg significantly reduced MT-induced oxidative stress by inhibiting lipid peroxidation, increasing the content of glutathion, and restoring the activities of superoxide dismutase and catalase. Biochemical and histological observations also showed a dose dependent hepatoprotective effect of Z. multiflora extract against subacute exposure to MT.

Mostafalou S., Abdollahi M.

Pesticides are a family of compounds which have brought many benefits to mankind in the agricultural, industrial, and health areas, but their toxicities in both humans and animals have always been a concern. Regardless of acute poisonings which are common for some classes of pesticides like organophosphoruses, the association of chronic and sub-lethal exposure to pesticides with a prevalence of some persistent diseases is going to be a phenomenon to which global attention has been attracted. In this review, incidence of various malignant, neurodegenerative, respiratory, reproductive, developmental, and metabolic diseases in relation to different routes of human exposure to pesticides such as occupational, environmental, residential, parental, maternal, and paternal has been systematically criticized in different categories of pesticide toxicities like carcinogenicity, neurotoxicity, pulmonotoxicity, reproductive toxicity, developmental toxicity, and metabolic toxicity. A huge body of evidence exists on the possible role of pesticide exposures in the elevated incidence of human diseases such as cancers, Alzheimer, Parkinson, amyotrophic lateral sclerosis, asthma, bronchitis, infertility, birth defects, attention deficit hyperactivity disorder, autism, diabetes, and obesity. Most of the disorders are induced by insecticides and herbicides most notably organophosphorus, organochlorines, phenoxyacetic acids, and triazine compounds.

Toledo-Ibarra G.A., Díaz Resendiz K.J., Ventura-Ramón G.H., González-Jaime F., Vega-López A., Becerril-Villanueva E., Pavón L., Girón-Pérez M.I.

Agricultural activity demands the use of pesticides for plague control and extermination. In that matter, diazinon is one of the most widely used organophosphorus pesticides (OPs). Despite its benefits, the use of OPs in agricultural activities can also have negative effects since the excessive use of these substances can represent a major contamination problem for water bodies and organisms that inhabit them. The aim of this paper was to evaluate oxidative damage in lipids and proteins of Nile tilapia (Oreochromis niloticus) exposed acutely to diazinon (0.97, 1.95 and 3.95ppm) for 12 or 24h. The evaluation of oxidative damage was determined by quantifying lipid hydroperoxides (Fox method) and oxidized proteins (DNPH method). The data from this study suggest that diazinon induces a concentration-dependent oxidative damage in proteins, but not lipids, of the liver and gills of Nile tilapia. Furthermore, the treatment leads to a decrease in the concentration of total proteins, which can have serious consequences in cell physiology and fish development.

Pourtaji A., Robati R.Y., Lari P., Hosseinzadeh H., Ramezani M., Abnous K.

Aim: Diazinon (DZN) is one of the most important organophosphorus compounds used to control pests in agriculture in many countries. Several studies have shown that exposure to DZN may alter protein expression in the liver. In order to further investigate the mechanism of DZN toxicity, differentially expressed ATP-interacting proteins, following subacute exposure to toxin, were separated and identified in rat liver. Main methods: Male rats were equally divided into four groups: control (corn oil) and DZN (15 mg/kg) by gavage once a day for 4 weeks. After homogenization of liver tissue, lysates were incubated ATP-sepharose beads. After several washes, ATP-interacting proteins were eluted and separated on 2-D polyacrylamide gels. Deferentially expressed proteins were cut and identified using matrix-assisted laser desorption/ionization/time-of-flight and Mascot database. Identified proteins were classified according to their biological process using protein analysis through evolutionary relationships (PANTHER) Web site. Key finding: In this work, we showed that several key proteins involved in biological processes such as antioxidant system, oxidative stress, apoptosis, and metabolism were differentially expressed after subacute exposure to DZN.

Saraei F., Sadoughi M., Kaka G., Sadraie S.H., Foaddodini M.

Ezzi L., Belhadj Salah I., Haouas Z., Sakly A., Grissa I., Chakroun S., Kerkeni E., Hassine M., Mehdi M., Ben Cheikh H.

This study aims to investigate the effects of chlorpyrifos’s sub-acute exposure on male rats. Two groups with six animals each were orally treated, respectively, with 3.1 mg/kg b w and 6.2 mg/kg b w of chlorpyrifos during 4 weeks. The genotoxic effect of chlopyrifos was investigated using the comet assay and the micronucleus test. Some hematological and liver’s histopathological changes were also evaluated. Results revealed that chlorpyrifos induced histopathological alterations in liver parenchyma. The lymphoid infiltration observed in liver sections and the increase in white blood cells parameter are signs of inflammation. A significant increase in the platelet’ count and in polychromatic erythrocytes/normochromatic erythrocytes (PCE/NCE) ratio was observed in chlorpyrifos-treated groups which could be due to the stimulatory effect of chlorpyrifos on cell formation in the bone marrow at lower doses. In addition, the increase of bone marrow micronucleus percentage and the comet tail length revealed a genotoxic potential of chlorpyrifos in vivo.

Xu M., Wang P., Sun Y., Wang H., Liang Y., Zhu L., Wu Y.

Organophosphates and pyrethroids are widely used pesticides with prominent toxicity to humans. However, their joint toxicity has not been thoroughly investigated. In this study, we investigated the oxidative damages induced by low dose dichlorvos (DDVP) and deltamethrin (DM), the representative organophosphate and pyrethroid, respectively, and their mixtures in the liver of rats for 90 consecutive days. Two oxidative stress markers, malondialdehyde (MDA) and protein carbonyl (PCO) levels, were measured to reflect the extent of lipid peroxidation and protein oxidation, respectively. DDVP, DM, and their mixtures induced levels of MDA and PCO dose-dependently, although no toxic signs and pathological changes of liver were found in the rats following 90-day exposure. DDVP and DM induced greater increase of MDA than PCO, which indicated that lipids were particularly sensitive to the oxidative damage. We found that DDVP, DM and their mixtures could inhibit the activity of two antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). The effects of DM on SOD activity, lipid peroxidation and protein oxidation were greater than those of DDVP. The combined effect of DDVP and DM was lower than the sum of their individual effects. Thus the interaction between dichlorvos and deltamethrin may be antagonistic on the induction of oxidative stress in rat liver.

Abdollahi M., Baeeri M., Karami-Mohajeri S.

Muranli F.D., Kanev M., Ozdemir K.

Abstract The aim of this study was to evaluate the genetic damage in human peripheral blood lymphocytes following 24 and 48- hour exposure to a commercial diazinon formulation Basudin 60EM® at concentrations between 0.01 and 40 μg mL-1. For this purpose we used the micronucleus (MN), fluorescence in situ hybridization (FISH), and alkaline single cell gel electrophoresis (comet) assay. Diazinon significantly increased the frequency of micronucleated cells compared to control. Forty-eight-hour exposure increased this frequency even at lower concentrations (0.01-10 μg mL-1). The FISH results revealed aneugenic effects at 10 μg mL-1. The comet assay also confirmed DNA damage at concentrations between 10 and 40 μg mL-1. Our findings have confirmed the genotoxic potential of diazinon and its cytotoxic effect on human lymphocytes. The increased DNA damage in our study raises concern about the current assessment of the health risk posed by this pesticide and calls for a high level of caution in agricultural and household use.

Lasram M.M., El-Golli N., Lamine A.J., Douib I.B., Bouzid K., Annabi A., El Fazaa S., Abdelmoula J., Gharbi N.

Organophosphorus pesticides are known to disturb glucose homeostasis and increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on insulin signaling pathways and the protective effects of N-acetylcysteine (NAC). Malathion (200 mg/kg) and NAC (2 g/l) were administered orally to rats, during 28 consecutive days. Malathion increases plasma glucose, plasma insulin and glycated hemoglobin levels. Further, we observed an increase of insulin resistance biomarkers and a decrease of insulin sensitivity indices. The GP, GSK3β and PEPCK mRNA expressions were amplified by malathion while, the expression of glucokinase gene is down-regulated. On the basis of biochemical and molecular findings, it is concluded that malathion impairs glucose homeostasis through insulin resistance and insulin signaling pathways disruptions in a way to result in a reduced function of insulin into hepatocytes. Otherwise, when malathion-treated rats were compared to NAC supplemented rats, fasting glucose and insulin levels, as well as insulin resistance indices were reduced. Furthermore, NAC restored liver GP and PEPCK expression. N-acetylcysteine showed therapeutic effects against malathion-induced insulin signaling pathways disruption in liver. These data support the concept that antioxidant therapies attenuate insulin resistance and ameliorate insulin sensitivity.

Beydilli H., Yilmaz N., Cetin E.S., Topal Y., Celik O.I., Sahin C., Topal H., Cigerci I.H., Sozen H.

Araoud M., Neffeti F., Douki W., Khaled L., Najjar M.F., Kenani A., Houas Z.

Massey N., Vasanthi S.S., Gimenez-Lirola L.G., Tyler H., Thippeswamy T.

Gust K.A., Amar S.K., Gut C.P., Styles R.M., Karna R.R., James R.A., Holtzapple D.M., Stricker J.L., McInturf S.M., Phillips E.A., Honnold C., Luo X., Mumy K.L., Mattie D.R., Chappell M.A., et. al.

Li X., Meng Z., Gong S., Liang Y., Zhang Y., Xu X., Wang Z., Wang S.

Ortiz-Delgado E., Bendezu-Quispe G., Soncco-Llulluy F., Li J., Rosales-Rimache J.

Chronic exposure to pesticides causes various adverse health effects, mainly at a neurological level. However, there is little evidence focused on liver tissue injury and transaminase activity as indicators of effect. A cross-sectional study was designed based on medical-occupational records of workers from an agro-export company in Peru to associate the levels of butyrylcholinesterase (BChE) transaminases (ALT and AST). Occupational medical records were reviewed to obtain demographic and occupational information and laboratory values of BChE activity and transaminases. We evaluated 459 records, and 69.9% were men. The mean age was 34.9 ± 11.5 years. BChE, ALT, and AST levels were 6238.8 ± 709.1 U/l, 34.4 ± 12.5 U/l, and 22.4 ± 8.5 U/l, respectively. The proportion of inhibited BCHE and elevated transaminase levels was 15.3% and 21.6%, respectively. We found a significant association between BChE inhibition and elevation of transaminases (AST: PR = 0.798, 95%CI: 0.716–0.889; ALT: PR = 0.419, 95%CI: 0.239–0.736). The potential usefulness of transaminases is shown as a biomarker of exposure and monitoring in occupational health programs for the agro-industry.

Udayakumar K.P., Priyatharshini M., Adhimoolam M., Ukkirapandian K., Theresa M., Murugesan S.B.

ABSTRACT Background: India is a land of agriculture, where the economy is based on cash crop cultivation. The wide and chronic use of pesticides for agriculture, domestic, and industrial purposes without protective measures has led to subsequent adverse health effects and further evaluation. It has become a major concern of public health due to its usage throughout the year among pesticide industrial workers, distributors and retail shopkeepers, agricultural field workers, and sprayers. Among the different types of pesticides (organochlorines, organophosphorus, carbamates, and pyrethroid compounds) used, quinalphos is the most common organophosphorus compound used in South India. These compounds were known to produce oxidative damage in the liver, kidney, bone marrow, brain, and intestine. Nonenzymatic antioxidants like vitamin C and E were found to alleviate the oxidative damage imposed by these pesticides. Thus, the present study aims to evaluate the effect of oral supplementation of vitamin E and vitamin C in comparison to exposure-free days on complete blood count, antioxidant enzymes, liver enzymes, and histopathological changes in the liver following exposure of male Wistar rats to quinalphos. Materials and Methods: This experimental study was done at XXXX after getting scientific and ethical committee clearance. A total of 24 adult male Wistar rats were divided randomly into four groups, with six in each group. Group A consists of animals not exposed to quinalphos for 60 days (control group), group B exposed to quinalphos for 60 days, group C exposed to quinalphos orally only for the first 30 days with exposure-free days for the next 30 days, and group D exposed to quinalphos orally for 60 days along with vitamin E and vitamin C oral supplementation. During exposure, quinalphos was administered at the dose of 3 mg/kg/day mixed with drinking water through oral gavage. Animals were sacrificed at the end of 60 days. Blood was collected by direct cardiac puncture, and the liver tissue was used for histopathological investigation. Data were analyzed with one-way ANOVA and post hoc Turkey’s test for intergroup comparison using SPSS 21.0 software. Results: RBC count (P = 0.011), Hb % (P = 0.000), and hematocrit (P = 0.000) were significantly reduced, whereas WBC count (P = 0.005) and neutrophil % (P = 0.001) significantly increased in the quinalphos-exposed group (group B) compared to other three groups. Liver enzymes, SGPT (P = 0.028) and SGOT (P = 0.343), were elevated, and the antioxidants catalase (P = 0.000) and glutathione peroxidase (P = 0.000) were significantly reduced in the quinalphos-exposed group when compared to the control and exposure free group. Histopathology of the liver showed diffuse necrosis of the hepatocytes with central venous congestion in quinalphos-exposed (group B) compared to the other three groups. The exposure-free group (group C) has shown better histopathological changes when compared to quinalphos exposure with (group D) and without (group B) vitamin C and E supplementation group. Conclusion: Quinalphos exposure orally results in anemia, leucocytosis with neutrophilia, liver damage, and oxidative stress. As evidenced by liver histopathology and altered antioxidant enzymes in the supplementation group compared to the group with exposure-free days, the toxic effects of quinalphos were less during exposure-free days. Thus, people occupationally exposed to quinalphos can alleviate the ill effects by having exposure-free days as interval breaks to remove the toxic accumulation of organophosphorus compounds.

López-Benítez A., Guevara-Lara A., Domínguez-Crespo M.A., Andraca-Adame J.A., Torres-Huerta A.M.

The extensive use of pesticides has led to the contamination of natural resources, sometimes causing significant and irreversible damage to the environment and human health. Even though the use of many pesticides is banned, these compounds are still being found in rivers worldwide. In this review, 205 documents have been selected to provide an overview of pesticide contamination in rivers over the last 10 years (2014–2024). After these documents were examined, information of 47 river systems was organized according to the types of pesticides most frequently detected, including organochloride, organophosphorus, and pyrethroid compounds. A total of 156 compounds were classified, showing that 46% of these rivers contain organochlorine compounds, while 40% exhibit organophosphorus pesticides. Aldrin, hexachlorocyclohexane, and endosulfan were the predominant organochlorine pesticides with concentration values between 0.4 and 37 × 105 ng L−1. Chlorpyrifos, malathion, and diazinon were the main organophosphorus pesticides with concentrations between 1 and 11 × 105 ng L−1. Comparing the pesticide concentrations with standard guidelines, we found that the Ganga River in India (90 ng L−1), the Owan and Okura Rivers in Nigeria (210 and 9 × 103 ng L−1), and the Dong Nai River in Vietnam (68 ng L−1) exceed the permissible levels of aldrin (30 ng L−1).

D R., AG T., S S., M K., Kumar Sharma G., CL M., Kumar D.

AbstractThe current study investigated the therapeutic potential of quercetin and quercetin nanoparticles in alleviating liver toxicity induced by ethion in Wistar albino rats. Quercetin nanoparticles were synthesized using the ionic‐gelation method. Rats were exposed to ethion alone (at high and low doses) or in combination with quercetin or quercetin nanoparticles. Ethion exposure led to significant decreases in organ weight, along with elevated levels of glucose, triglycerides, total cholesterol, low‐density lipoprotein, and acid phosphatase, and reduced high‐density lipoprotein in serum. Hepatocellular biomarker enzymes were increased in the ethion‐exposed group, while antioxidant enzyme levels were decreased. Histopathological analysis revealed fatty changes, degeneration, and hemorrhages in the liver. Co‐administration of quercetin nanoparticles mitigated these effects, potentially by neutralizing reactive oxygen species generated by ethion. Molecular docking studies suggested a strong interaction between quercetin and Cyp2E1, implicating a role in detoxification. This study highlights the potential of nanoquercetin as a therapeutic supplement for pesticide intoxication management.

Taychaworaditsakul W., Sawong S., Intatham S., Chansakaow S., Kunnaja P., Chewonarin T., Jaijoy K., Wittayapraparat A., Yusuk P., Sireeratawong S.

Litsea martabanica root’s antioxidant and acetylcholinesterase (AChE) activity showed promise as a pesticide detoxification agent in our previous study. In addition to its root, leaves can help alleviate pesticide exposure, although there is limited scientific evidence supporting their efficacy. However, the use of roots in several countries, such as Thailand, could contribute to environmental degradation, as highland communities traditionally used leaves instead of roots. This study aims to evaluate the antioxidant activity and anti-pesticide potential of water extract from L. martabanica leaves through in vitro and in vivo investigations. In the in vitro study, L. martabanica water extract and its fractions demonstrated antioxidant activity and induced apoptosis in hepatic satellite cells. In the in vivo study, treatment with the leaf extract led to increased AChE activity, decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) levels, and reduced glutathione in chlorpyrifos-exposed rats. Histopathological examination revealed that chlorpyrifos-treated rats exhibited liver cell damage, while treatment with the water extract of L. martabanica exhibited a protective effect on the liver. In conclusion, L. martabanica water extract exhibited antioxidant activity, enhanced AChE activity, and improved histopathological abnormalities in the liver.

Oskoei P., Guilherme S., Oliveira H.

Population growth leads to the need for more efficient techniques and compounds in agriculture, such as pesticides, to deal with the ever-growing demand. Pesticides may end up in the environment, often compromising the ecosystem affecting all organisms including humans. Therefore, the consequences of exposure to these compounds to biota and humans needs to be assessed. Bearing this in mind, the aim of this study was to examine the in vitro cytotoxicity and genotoxicity attributed to exposure to the biopesticide Turex® utilizing the liver cell line HepG2. Cells were incubated with biopesticide Turex® at 250, 500, 1000, 1500 or 2000 μg/L in both non-activated and activated forms for 24 and 48 h. Subsequent effects on cell viability were assessed using the MTT. The influence on cell cycle dynamics was determined by flow cytometry, while DNA damage was measured by the comet assay. Data demonstrated that activated Turex® induced cytotoxicity and DNA damage after 48 h in HepG2 cell line. The cell cycle progression was not markedly affected by Turex® at any concentration or duration of exposure. In conclusion, data demonstrated the potential adverse effects attributed to exposure to biopesticide Turex® in human cell line HepG2. Consequently, this type of biopesticide needs to be further investigated to determine the potential adverse in vivo effects on various non-target organisms.

Chu B., Lin C., Nie P., Xia Z.

Surface-enhanced Raman scattering (SERS) technology has unique advantages in the rapid detection of pesticides in plant-derived foods, leading to reduced detection limits and increased accuracy. Plant-derived Chinese herbal medicines have similar sources to plant-derived foods; however, due to the rough surfaces and complex compositions of herbal medicines, the detection of pesticide residues in this context continues to rely heavily on traditional methods, which are time consuming and laborious and are unable to meet market demands for portability. The application of flexible nanomaterials and SERS technology in this realm would allow rapid and accurate detection in a portable format. Therefore, in this review, we summarize the underlying principles and characteristics of SERS technology, with particular focus on applications of SERS for the analysis of pesticide residues in agricultural products. This paper summarizes recent research progress in the field from three main directions: sample pretreatment, SERS substrates, and data processing. The prospects and limitations of SERS technology are also discussed, in order to provide theoretical support for rapid detection of pesticide residues in Chinese herbal medicines.

Watson C.J., Whitledge J.D., Chai P.R.

Vasetska O.P., Lisovska V.S., Prodanchuk M.H., Zhminko P.H.

The effect of concomitant pesticides and plant growth regulators on humans is still not well understood. N-oxide-2,6-dimethylpyridine (Ivin) is the plant growth regulator known to reduce the acute toxicity of pesticides, but its protective mechanisms need to be investigated. The aim of the study was to assess the hepatoprotective ability of 2,6-dimethylpyridine N-oxide (Ivin) using a model of acute CCl4-induced hepatitis. Male Wistar Han rats received two subcutaneous CCl4 injections (0.8 ml/100 g b.w.). Oral Ivin (13 or 0.13 mg/kg) and hepatoprotector “Silybor-35” (5 mg/kg) as reference substances were administered orally one hour pre- and 2 hours post-CCl4 injection. The biochemical assay of blood plasma, estimation of lipid peroxidation products in the liver tissue and histological liver analysis were done. The results of functional tests and histomorphological studies of liver tissue demonstrated that Ivin exhibited a pronounced hepatoprotective effect, more pronounced when it was administered at a low 0.13 mg/kg dose. Calculation of the hepatoprotection efficiency index for Ivin showed that it was comparable to that for “Silybor-35”. Keywords: hepatoprotective effect, Ivin, СCl4-induced hepatitis of rats

Bunsri S., Muenchamnan N., Naksen W., Ong-Artborirak P.

Pesticide-related health concerns are a global public health issue. Few studies in Thailand have explored the hematological and biochemical effects of occupational pesticide exposure. The goal of this study was to investigate the effects of pesticides on the hematology, hepatic, and renal function of Thai vegetable farmers. A cross-sectional study was carried out in Chiang Mai, northern Thailand. A total of 124 apparently healthy vegetable farmers were interviewed about their lifetime exposure to agricultural pesticides. Blood samples were collected via venipuncture to be tested for complete blood count (CBC), liver function, and kidney function. Approximately 46% of the farmers were pesticide users who reported a history of pesticide use for their crops, while 54% were non-pesticide users. In the male farmers, the activities of aspartate aminotransferase (AST), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were significantly higher in the pesticide users compared to the non-pesticide users, while the estimated glomerular filtration rate (eGFR), hematocrit (HCT), and red blood cells (RBC) were significantly lower (p < 0.05). In the females, the pesticide users had significantly higher levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and MCHC than the non-pesticide users (p < 0.05). Pesticide use among Thai vegetable farmers may cause hematological alterations and increase the risk of hepatic and renal dysfunction. Some hematological and biochemical parameters may be used for monitoring to protect them from the adverse health effects of occupational exposure to pesticides.

Ivanović S.R., Borozan N., Miladinović D.Ć., Živković I., Borozan S.

Diazinon is an organophosphate pesticide (OP) that has significant potential for accidental and intentional poisoning of wildlife, domestic animals and humans. The aim of the study is to investigate the correlation between cholinesterase activity and oxidative stress parameters in liver and diaphragm by continuous monitoring as a function of time during prolonged use of diazinon. Wistar rats were treated orally with diazinon (55 mg/kg/day): 7, 14, 21 and 28 days. At the end of each period, blood, liver and diaphragm were collected to examine cholinesterase activity and enzymatic/non-enzymatic oxidative stress parameters: superoxide dismutase 1 (SOD1), catalase (CAT), thiobarbituric acid substances (TBARS), protein carbonyl groups. In all four time periods, there was a significant change in acetylcholinesterase (AChE) in erythrocytes and butyrylcholinesterase (BuChE) in blood plasma, CAT in liver and diaphragm and SOD1 in diaphragm. Parameters significantly altered during the cholinergic crisis included: cholinesterases and TBARS in liver and diaphragm and partially SOD1 in liver. Protein carbonyl groups in liver and diaphragm were significantly altered outside the cholinergic crisis. In the liver, there was a very strong negative correlation between BuChE and TBARS in all four time periods and BuChE and CAT on day 7. In the diaphragm, a very strong negative correlation was found between AChE and TBARS at days 7 and 14, and a very strong positive correlation between AChE and SOD1 at days 14, 21 and 28. A better understanding of the relationship between cholinergic overstimulation and oxidative stress may help to better assess health status in prolonged OPs intoxication.

Liu C., Li J., Qi X., Wang L., Sun D., Zhang J., Zhang K., Li J., Li Y., Wen H.

Cytochrome P450s (CYPs), as one of the most diverse enzyme superfamilies in nature, play critical functions in antioxidant reactions against endogenous and exogenous compounds. In this study, we performed genome-wide characterization of CYP superfamily members and analyzed their expression patterns under several abiotic stresses in spotted sea bass, which is known as an economically important fish species in the Chinese aquaculture industry. A total of 55 CYP genes were identified and divided into 17 families within 10 clans. The analysis of phylogeny, gene structure, and syntenic relationships provided evidence for the evolution of CYP genes and confirmed their annotation and orthology. The expression of CYP genes was examined in the liver during trichlorfon stress using quantitative real-time PCR. The results showed that 20 tested CYP genes displayed significant mRNA expression changes, indicating that they may play crucial roles in the metabolism of trichlorfon and can be potential biomarkers for trichlorfon pollution. Moreover, by screening transcriptomic databases, 10, 3 and 19 CYP genes exhibited differential expression patterns in response to hypoxia, alkalinity and heat stress, respectively. Taken together, this study provided insights into the regulation of CYP genes by toxicological and environmental stresses, laid basis for extensive functional studies of the CYP superfamily in spotted sea bass and other teleost species.