A portable europium complex-loaded fluorescent test paper combined with smartphone analysis for the on-site and visual detection of mancozeb in food samples.

The on-site detection of mancozeb in food samples holds immense value for food safety. A red-fluorescent europium complex (Eu-PYDC-Phen) has been prepared and employed as a fluorescence probe for mancozeb detection. The optimized probe suspension exhibits excellent detection performances, including a wide linear range (0-0.24 mM), low detection limit (65 nM), rapid response (2 mins) and high selectivity. Moreover, a portable detection platform was carefully designed, integrating the Eu-PYDC-Phen-based fluorescent test strips with smartphone color recognition software. This innovative platform enables visual and on-site detection of mancozeb in tomato, apple, and lettuce, achieving satisfactory recovery rates (90.34 to 106.50%). Furthermore, the integration of machine learning techniques based on hierarchical clustering algorithm has the potential to further improve the prediction and decision-making efficiency in mancozeb detection. This work provides an economical, convenient, and reliable strategy for on-site detection of pesticide in agricultural products, thereby making a meaningful contribution to food safety.

Fabrication of versatile Fe3O4/GO/Au composite nanomaterial as SERS-active substrate for detection of pesticide residue.

Highly active Fe3O4/GO/Au composite nanomaterial was fabricated as a substrate of surface-enhanced Raman spectroscopy (SERS) and applied for pesticide residue detection. The three-layer multifunctional Fe3O4/GO/Au nanoparticles (NPs) were designed by facile method, with high hotspots, and were characterized by various techniques, including ultraviolet spectrophotometry (UV), X-ray diffraction (XRD), infrared absorption spectrometer (IR), and transmission electron microscopy (TEM). The performance of Fe3O4/GO/Au was evaluated by Raman spectroscopy with R6G as a probe molecule to verify its enhancement effect. It exhibited a strong Raman signal with 10-6 M of R6G. Furthermore, the presence of Fe3O4/GO/Au nanohybrid enabled the SERS-based method to detect mancozeb and showed an excellent linear relationship in the range of 0.25-25 ppm, with a low limit of detection (0.077 ppm), satisfactory EF, stability, and repeatability. In addition, the mechanism of SERS enhancement with electromagnetic mechanism (EM) and chemical mechanism (CM) was discussed in detail. Therefore, the proposed SERS approach holds promise as an auxiliary technique for screening contaminated agricultural products, environmental sample, and food in the future.

Effects of captan, mancozeb and azoxystrobin fungicides on motility, oxidative stress and fatty acid profiles in rainbow trout (Oncorhynchus mykiss) spermatozoa.

An in vitro study using rainbow trout spermatozoa was designed to evaluate the toxic effects of different concentrations of captan (CPT), mancozeb (MCZ), and azoxystrobin (AZX) fungicides on motility parameters, lipid peroxidation, SOD activity, total antioxidant capacity (TAC), and DPPH inhibition. Moreover, changes in fatty acids profiles caused by the fungicides were determined for the first time. The results revealed that motility parameters, SOD activities, TAC values, and DPPH inhibitions decreased significantly while lipid peroxidation increased after ≥2 µg/L of CPT, ≥1 µg/L of MCZ, and ≥5 µg/L of AZX incubations for 2 h at 4 °C. Additionally, 10 µg/L CPT, 5 µg/L MCZ, and 200 µg/L AZX reduced motility to the 50 % level. Our results clearly demonstrated significant changes in the fatty acids profiles of spermatozoa exposed to these concentrations of the fungicides. The highest lipid peroxidation and the lowest monounsaturated and polyunsaturated saturated fatty acids (MUFA and PUFA, respectively) were detected in AZX. Even though the susceptibility of spermatozoa to oxidative damage is generally attributed to PUFA contents, the results of this study have represented that MUFA content could play a part in this tendency. Moreover, the lower concentration of MCZ reduced motility to the % 50 level while it deteriorated the fatty acids profile less than did AZX. Overall, the present study demonstrated that the detrimental effects of the fungicides on mitochondrial respiration and related enzymes have more priority than oxidative stress in terms of their toxicities on spermatozoa. It has also been suggested that fish spermatozoa are a good model for determining changes in the fatty acid profiles by fungicides, probably, by other pesticides and environmental contaminants as well.

Mancozeb induces cytogenotoxicity in meristematic cells of Allium cepa L.

Mancozeb is a fungicide of the dithiocarbamate functional group, and it is widely used in agriculture to control various fungal diseases. Thus, studies detailing its toxicological characteristics are necessary, as the population may be exposed through the consumption of food or water contaminated with mancozeb. The aim of this study was to evaluate the cytotoxic, genotoxic, and mutagenic potentials of this dithiocarbamate using the Allium cepa L. test system as well as its cytotoxicity in erythrocytes of female rats (Rattus norvegicus). The meristematic roots of A. cepa bulbs were exposed to various concentrations of mancozeb (62.5, 125, 250, and 500 mg/L) for 24, 48, and 72 h to determine cytotoxicity by evaluating the mitotic index (MI), chromosomal aberrations (CA), and nuclear anomalies (NA) for genotoxicity analysis and micronuclei (MN) for mutagenicity analysis. Distilled water and copper sulfate (0.0006 mg/L) were used as the negative control (NC) and positive control (PC), respectively. The MI and the sum of CA and NA of all the mancozeb concentrations showed a significant difference (p ≤ 0.05) in relation to the NC, indicating possible cytotoxicity and genotoxicity induced by mancozeb. Additionally, MN significantly increased with mancozeb concentration from 250 mg/L to 500 mg/L in 24 h when compared to NC. In another study model, mancozeb showed to be cytolytic at concentrations starting from 125 mg/L. Therefore, these results indicate that mancozeb causes cytogenetic alterations and mutagenicity at lower concentrations than those used in agriculture, which emphasizes the need for more care when managing this fungicide.

Occupational exposure to pesticides and neurobehavioral outcomes. Impact of different original and recalled exposure measures on the associations.

BACKGROUND: Several measures of occupational exposure to pesticides have been used to study associations between exposure to pesticides and neurobehavioral outcomes. This study assessed the impact of different exposure measures for glyphosate and mancozeb on the association with neurobehavioral outcomes based on original and recalled self-reported data with 246 smallholder farmers in Uganda. METHODS: The association between the 6 exposure measures and 6 selected neurobehavioral test scores was investigated using linear multivariable regression models. Exposure measures included original exposure measures for the previous year in 2017: (i) application status (yes/no), (ii) number of application days, (iii) average exposure-intensity scores (EIS) of an application and (iv) number of EIS-weighted application days. Two additional measures were collected in 2019: (v) recalled application status and (vi) recalled EIS for the respective periods in 2017. RESULTS: Recalled applicator status and EIS were between 1.2 and 1.4 times more frequent and higher for both pesticides than the original application status and EIS. Adverse associations between the different original measures of exposure to glyphosate and 4 neurobehavioral tests were observed. Glyphosate exposure based on recalled information and all mancozeb exposure measures were not associated with the neurobehavioral outcomes. CONCLUSIONS: The relation between the different original self-reported glyphosate exposure measures and neurobehavioral test scores appeared to be robust. When based on recalled exposure measures, associations observed with the original exposure measures were no longer present. Therefore, future epidemiological studies on self-reported exposure should critically evaluate the potential bias towards the null in observed exposure-response associations.

Investigation on the mancozeb toxicity in adult zebrafish (Danio rerio).

Agriculture has gained increasing importance in response to the continuous growth of the world population and constant need for food. To avoid production losses, farmers commonly use pesticides. Mancozeb is a fungicide used in agriculture as this compound is effective in combating fungi that harm crops. However, this fungicide may also produce damage to non-target organisms present in soil and water. Therefore, this study aimed to investigate the influence of exposure to mancozeb on survival rate, locomotor activity, behavior, and oxidative status utilizing adult zebrafish (Danio rerio) as a model following exposure to environmentally relevant concentrations of this pesticide. The experimental groups were negative control, positive control, and mancozeb (0.3; 1.02; 3.47; 11.8 or 40 µg/L). Zebrafish were exposed to the respective treatments for 96 hr. Exposure to mancozeb did not markedly alter survival rate and oxidative status of Danio rerio. At a concentration of 11.8 µg/L, the fungicide initiated changes in locomotor pattern of the animals. The results obtained suggest that the presence of mancozeb in the environment might produce locomotor alterations in adult zebrafish, which subsequently disrupt the animals' innate defense mechanisms. In nature, this effect attributed to mancozeb on non-target organisms might result in adverse population impacts and ecological imbalance.

Low concentrations of ethylene bisdithiocarbamate pesticides maneb and mancozeb impair manganese and zinc homeostasis to induce oxidative stress and caspase-dependent apoptosis in human hepatocytes.

The worldwide and intensive use of phytosanitary compounds results in environmental and food contamination by chemical residues. Human exposure to multiple pesticide residues is a major health issue. Considering that the liver is not only the main organ for metabolizing pesticides but also a major target of toxicities induced by xenobiotics, we studied the effects of a mixture of 7 pesticides (chlorpyrifos-ethyl, dimethoate, diazinon, iprodione, imazalil, maneb, mancozeb) often detected in food samples. Effects of the mixture was investigated using metabolically competent HepaRG cells and human hepatocytes in primary culture. We report the strong cytotoxicity of the pesticide mixture towards hepatocytes-like HepaRG cells and human hepatocytes upon acute and chronic exposures at low concentrations extrapolated from the Acceptable Daily Intake (ADI) of each compound. Unexpectedly, we demonstrated that the manganese (Mn)-containing dithiocarbamates (DTCs) maneb and mancozeb were solely responsible for the cytotoxicity induced by the mixture. The mechanism of cell death involved the induction of oxidative stress, which led to cell death by intrinsic apoptosis involving caspases 3 and 9. Importantly, this cytotoxic effect was found only in cells metabolizing these pesticides. Herein, we unveil a novel mechanism of toxicity of the Mn-containing DTCs maneb and mancozeb through their metabolization in hepatocytes generating the main metabolite ethylene thiourea (ETU) and the release of Mn leading to intracellular Mn overload and depletion in zinc (Zn). Alteration of the Mn and Zn homeostasis provokes the oxidative stress and the induction of apoptosis, which can be prevented by Zn supplementation. Our data demonstrate the hepatotoxicity of Mn-containing fungicides at very low doses and unveil their adverse effect in disrupting Mn and Zn homeostasis and triggering oxidative stress in human hepatocytes.

Residue behaviour and health risk assessment of chlorpyrifos and mancozeb in apple fruits and soil.

Mancozeb residue estimation was done using second derivative ultraviolet spectroscopy by Shimadzu ultraviolet-visible spectrophotometer, and chlorpyrifos was estimated by QuEChERS technique using GC-FPD. The persistence for chlorpyrifos was carried out at two locations, and for mancozeb, persistence studies were carried out at four locations. Initial deposits of mancozeb on apple fruits ranged from 1.33 to 1.63 mg/kg at the recommended dose and from 2.55 to 3.26 mg/kg at double the recommended dose at all four locations. Chlorpyrifos residues in apple fruits had an initial deposit of 0.94-0.99 mg/kg at recommended dose and 1.75-1.92 mg/kg at double the recommended dose. Mancozeb residues in apple fruit were below the detection limit (BDL) after 20 days at recommended dose and after 25 days at double the recommended dose at two locations, while mancozeb residue at the other two locations and the residues of chlorpyrifos at all locations reached BDL after 15 and 20 days at recommended and double the recommended doses, respectively. Half-life of mancozeb varied from 3.07 to 4.02 days at recommended dose and from 3.30 to 4.32 days at double the recommended dose, whereas chlorpyrifos residues dissipated to half their initial concentration on 2.33-2.35 days at recommended dose and 2.89-2.90 days at double the recommended dose. The soil samples showed no presence of residues of chlorpyrifos and mancozeb at harvest. The risk assessment revealed that hazard quotient for the intake of mancozeb was in the range of 0.06-0.13% and 0.20-0.44% for rural and urban population, while for the intake of chlorpyrifos, hazard quotient was in the range of 0.10-0.12% for rural population and 0.33-0.38% for urban population, and theoretical maximum dietary intake (9.67 × 10-5 mg/person and 3.18 × 10-4 mg/person for rural population and urban population in case of mancozeb and 3.22 × 10-5 mg/person and 1.06 × 10-4 mg/person for rural population and urban population in case of chlorpyrifos) was also found to be less than maximum permissible intake (1.38 mg/kg for mancozeb and 0.60 mg/kg for chlorpyrifos). The results of risk assessment thereby indicated that apple consumption does not pose a risk to human health.

Potential role of dietary Boswellia serrata resin against mancozeb fungicide-induced immune-antioxidant suppression, histopathological alterations, and genotoxicity in Nile tilapia, Oreochromis niloticus.

This study was established to look into the toxicological consequences of chronic exposure to a fungicide (mancozeb; MAZ) on the immune-antioxidant response, gene expressions, hepato-renal functions, and histological pictures of Nile tilapia (Oreochromis niloticus). Additionally, the effectiveness of Indian frankincense resin extract (IFRE) to mitigate their toxicity was taken into account. Fish (n =240; average body weight: 22.45 ± 2.21 g) were randomized into four groups for eight weeks in six replicates (control, IFRE, MAZ, and IFRE + MAZ), where ten fish were kept per replicate. The control and IFRE groups received basal diets that included 0.0 and 5 g/kg of IFRE without MAZ exposure. The MAZ and IFRE+MAZ groups received the same diets and were exposed to 1/10 of the 96-h of LC50 of MAZ (1.15 mg/L). The outcomes displayed that MAZ exposure resulted in a lower survival rate (56.67 %) and significantly decreased levels of immune-antioxidant variables (antiprotease, complement3, phagocytic activity, lysozyme, glutathione peroxidase, superoxide dismutase, and total antioxidant capacity) compared to the control group. The MAZ-exposed fish showed the greatest levels of lipid peroxide (malondialdehyde), alkaline phosphatase, alanine amino-transferase, and stress indicators (cortisol and glucose). Additionally, histopathological alterations, including vacuolation, severe necrosis, degeneration, and mononuclear cell infiltrations in the hepatic, renal, and splenic tissues resulted, besides a reduction in the melanomacrophage center in the spleen. A down-regulation of immune-antioxidant-associated genes [toll-like receptors (TLR-2 and TLR-7), nuclear factor kappa beta (NF-κß), transforming growth factor-beta (TGF-ß), phosphoinositide-3-kinase regulatory subunit 3 gamma b (pik3r3b), interleukins (IL-1ß and IL-8), glutathione synthetase (GSS), glutathione peroxidase (GPx), and superoxide dismutase (SOD)] were the consequences of the MAZ exposure. Remarkably, the dietary inclusion of IFRE in MAZ-exposed fish augmented the immune-antioxidant parameters, including their associated genes, decreased stress response, and increased survival rate (85 %) compared with the MAZ-exposed fish. Moreover, dietary IFRE improved hepato-renal function indices by preserving the histological architecture of the hepatic, renal, and splenic tissues. The insights of this study advocate the use of an IFRE-dietary addition to protect Nile tilapia from MAZ toxicity, which provides perspectives for future implementations in enhancing fish health for sustainable aquaculture.

Replacing Mancozeb with Alternative Fungicides for the Control of Late Blight in Potato.

Mancozeb (MZ) is a broadly used fungicide for the control of plant diseases, including late blight in potatoes caused by the oomycete Phytophthora infestans (Mont.) De Bary. MZ has been banned for agricultural use by the European Union as of January 2022 due to its hazards to humans and the environment. In a search for replacement fungicides, twenty-seven registered anti-oomycete fungicidal preparations were evaluated for their ability to mitigate the threat of this disease. Fourteen fungicides provided good control (≥75%) of late blight in potted potato and tomato plants in growth chambers. However, in Tunnel Experiment 1, only three fungicides provided effective control of P. infestans in potatoes: Cyazofamid (Ranman, a QiI inhibitor), Mandipropamid (Revus, a CAA inhibitor), and Oxathiapiprolin + Benthiavalicarb (Zorvek Endavia, an OSBP inhibitor + CAA inhibitor). In Tunnel Experiment 2, these three fungicides were applied at the recommended doses at 7-, 9-, and 21-day intervals, respectively, totaling 6, 4, and 2 sprays during the season. At 39 days post-inoculation (dpi), control efficacy increased in the following order: Zorvec Endavia > Ranman > Revus > Mancozeb. Two sprays of Zorvec Endavia were significantly more effective in controlling the blight than six sprays of Ranman or four sprays of Revus. We, therefore, recommend using these three fungicides as replacements for mancozeb for the control of late blight in potatoes. A spray program that alternates between these three fungicides may be effective in controlling the disease and also in avoiding the build-up of resistance in P. infestans to mandipropamid and oxathiapiprolin.

Effects of glyphosate, mancozeb and their combinations on mouse neuroblastoma cells.

Pesticides-related toxicities have long been studied. Data regarding the effects of combined exposure to environmentally relevant pesticides however remain lacking. The herbicide glyphosate and the fungicide mancozeb are extensively used in agriculture. Residues of both compounds are frequently found in food and water and therefore, environmental exposure to both pesticides is a possibility. Neurotoxicity of glyphosate, mancozeb and their combinations were investigated using mouse neuroblastoma cells. Cytotoxicity observed with the glyphosate and mancozeb combinations was higher than that observed when glyphosate was tested alone. Combinations of glyphosate followed by mancozeb increased copper, manganese, and zinc levels. Mixture of mancozeb + glyphosate increased manganese and zinc levels. Combination of mancozeb followed by glyphosate increased copper and zinc levels. Glutathione ratio was decreased as a result of combinations of glyphosate and mancozeb. The decrease in glutathione ratio was greater in the combination groups than in glyphosate alone.

Neuroprotective Effect of White Nelumbo nucifera Gaertn. Petal Tea in Rats Poisoned with Mancozeb.

Nelumbo nucifera Gaertn. (N. nucifera) tea is used as food and folk medicine to reduce toxicity in Southeast Asia. Mancozeb (Mz) is used for controlling fungi in agriculture and contains heavy metals. This study aimed to examine the effect of white N. nucifera petal tea on cognitive behavior, hippocampus histology, oxidative stress, and amino acid metabolism in rats poisoned with mancozeb. Seventy-two male Wistar rats were divided into nine groups (n = 8 in each). Y-maze spontaneous alternation test was used to assess cognitive behavior, and amino acid metabolism was investigated by nuclear magnetic resonance spectroscopy (1H-NMR) from blood. There was a significant increase in relative brain weight in the Mz co-administered with the highest dose (2.20 mg/kg bw) of white N. nucifera group. The levels of tryptophan, kynurenine, picolinic acid, and serotonin in blood showed a significant decrease in the Mz group and a significant increase in the Mz co-administered with low dose (0.55 mg/kg bw) of white N. nucifera group. However, there was no significant difference in cognitive behavior, hippocampus histology, oxidative stress, and corticosterone. This study demonstrated that a low dose of white N. nucifera petal tea has a neuroprotective effect against mancozeb.

Effects of Nelumbonucifera Gaertn. Petal Tea Extract on Hepatotoxicity and Oxidative Stress Induced by Mancozeb in Rat Model.

Mancozeb (Mz) is one of the most widely used pesticides that has been reported to cause adverse human health risks. White Nelumbo nucifera (N. nucifera) petals have therapeutic properties to prevent toxicity. Hence, this study attempted to determine the effects of N. nucifera extract on hepatotoxicity and oxidative stress in mancozeb-treated rats. Seventy-two male rats were divided into nine groups and designed with a control; N. nucifera extract was administered at the doses of 0.55, 1.1, and 2.2 mg/kg bw/day, Mz was administered at 500 mg/kg bw/day, and the co-treatment groups (N. nucifera and Mz) were administered 0.55, 1.1, and 2.2 mg/kg bw/day of N. nucifera followed by administering Mz 500 mg/kg bw/day daily for 30 days. The results showed that all doses of N. nucifera extract did not induce hepatic toxicity and could suppress the toxicity of mancozeb by increasing body weight gain and decreasing relative liver weight, lobular inflammation, and total injury score. The combination treatment also decreased the molecular markers of oxidative stress (2-hydroxybutyric acid, 4-hydroxynonenal, l-tyrosine, pentosidine, and N6-carboxymethyllysine). Furthermore, the reduced glutathione and oxidized glutathione contents were adjusted close to the normal level. Therefore, N. nucifera extract is a natural antioxidant supplement that could decrease the toxicity of mancozeb and can be safely consumed.

Low level mancozeb exposure causes copper bioaccumulation in the renal cortex of rats leading to tubular injury.

Mancozeb is a widely-used, broad-spectrum contact dithiocarbamate fungicide. Dithiocarbamates are known to trans-chelate metals. This study was designed to evaluate the potential of Mancozeb to mobilize and bioaccumulate essential trace metals in various tissues. Long-Evans rats were orally gavaged with 0, 50, or 100 mg/kg/day of Mancozeb for 28 days. Mancozeb caused a significant increase in copper and manganese in the hippocampus and manganese in the liver. Exceedingly higher level of copper was detected in the renal cortex using ICP-OES in both dose groups. This was confirmed histologically in the tubular epithelial cells. In addition, copper-associated protein levels were also increased. Copper bioaccumulation in the renal cortex was accompanied by oxidative damage and tubular insult indicated by increased 4-HNE, KIM-1, and NGAL immunoreactivity. These findings demonstrate that low-dose Mancozeb exposure is a potential risk for kidney injury due to copper overload and warrants further in vivo and human population-based investigations.

Ultrastructural Evaluation of Mouse Oocytes Exposed In Vitro to Different Concentrations of the Fungicide Mancozeb.

Mancozeb is a widely used fungicide, considered to be an endocrine disruptor. In vivo and in vitro studies evidenced its reproductive toxicity on mouse oocytes by altering spindle morphology, impairing oocyte maturation, fertilization, and embryo implantation. Mancozeb also induces dose-dependent toxicity on the ultrastructure of mouse granulosa cells, including chromatin condensation, membrane blebbing, and vacuolization. We evaluated the effects on the ultrastructure of mouse oocytes isolated from cumulus-oocyte complexes (COCs), exposed in vitro to increasing concentrations of mancozeb. COCs were matured in vitro with or without (control) low fungicide concentrations (0.001-1 µg/mL). All mature oocytes were collected and prepared for light and transmission electron microscopy. Results showed a preserved ultrastructure at the lowest doses (0.001-0.01 µg/mL), with evident clusters of round-to-ovoid mitochondria, visible electron-dense round cortical granules, and thin microvilli. Mancozeb concentration of 1 µg/mL affected organelle density concerning controls, with a reduction of mitochondria, appearing moderately vacuolated, cortical granules, and microvilli, short and less abundant. In summary, ultrastructural data revealed changes mainly at the highest concentration of mancozeb on mouse oocytes. This could be responsible for the previously described impaired capability in oocyte maturation, fertilization, and embryo implantation, demonstrating its impact on the reproductive health and fertility.

Interaction between Six Waxy Components in Summer Black Grapes (Vitis vinifera) and Mancozeb and Its Effect on the Residue of Mancozeb.

Mancozeb, an antifungal typically used for the growth of fruits, has the characteristic of non-internal absorption, and has a risk of binding to the waxy components of fruits. This work investigated the interaction of pesticide molecules with the waxy layer on the grape surface and their effects on pesticide residues in grapes. The study observed significant changes in the compositions of the waxy layer on the grape surface after soaking in a mancozeb standard solution. The six substances-oleanolic acid, ursolic acid, lupeol, octacosanol, hexacosanal, and γ-sitosterol-with discernible content differences were chosen for molecular docking. Docking results were further visualized by an independent gradient model based on Hirshfeld partition (IGMH). Hydrogen bonds and van der Waals forces were found between mancozeb and the six waxy components. Moreover, the negative matrix effects caused by the presence or absence of wax for the determination of mancozeb were different through the QuEChERS-HPLC-MS method. Compared with the residue of mancozeb in grapes (5.97 mg/kg), the deposition of mancozeb in grapes after dewaxing was significantly lower (1.12 mg/kg), which further supports that mancozeb may interact with the wax layer compositions. This work not only provides insights into the study of the interaction between pesticides and small molecules but also provides theoretical guidelines for the investigation of the removal of pesticide residues on the surface of fruits.

Mancozeb-induced cytotoxicity in human erythrocytes: enhanced generation of reactive species, hemoglobin oxidation, diminished antioxidant power, membrane damage and morphological changes.

Mancozeb is an ethylene bis-dithiocarbamate fungicide extensively used in agriculture to safeguard crops from various fungal diseases. The general population is exposed to mancozeb through consumption of contaminated food or water. Here, we have investigated the effect of mancozeb on isolated human erythrocytes under in vitro conditions. Erythrocytes were treated with different concentrations of mancozeb (0, 5, 10, 25, 50, 100 µM) and incubated for 24 h at 37 °C. Analysis of biochemical parameters and cell morphology showed dose-dependent toxicity of mancozeb in human erythrocytes. Mancozeb treatment caused hemoglobin oxidation and heme degradation. Protein and lipid oxidation were enhanced, while a significant decrease was seen in reduced glutathione and total sulfhydryl content. A significant increase in the generation of reactive oxygen and nitrogen species was detected in mancozeb-treated erythrocytes. The antioxidant capacity and the activity of key antioxidant enzymes were greatly diminished, while crucial metabolic pathways were inhibited in erythrocytes. Damage to the erythrocyte membrane on mancozeb treatment was apparent from increased cell lysis and osmotic fragility, along with the impairment of the plasma membrane redox system. Mancozeb also caused morphological alterations and transformed the normal discoid-shaped erythrocytes into echinocytes and stomatocytes. Thus, mancozeb induces oxidative stress in human erythrocytes, impairs the antioxidant defense system, oxidizes cellular components, that will adversely affect erythrocyte structure and function.

Ameliorative effect of resveratrol against cymoxanil-mancozeb induced toxicity in rats.

This study was conducted to evaluate the cymoxanil-mancozeb (CM) toxicity and investigate the ameliorative effect of resveratrol (Res) against cymoxanil-mancozeb toxicity. Forty rats were divided into four groups; the first group was used as a control group, the second group was exposed to Res only at a dose of 20 mg/kg body weight for 4 weeks, and the third group was administered CM only at a dose of 799 mg/kg body weight for 4 weeks, The fourth group was co-treated with Res+CM for 4 weeks. Blood samples were analyzed for hematological and biochemical parameters. The comet assay was done on liver and blood specimens and histopathological examinations of the liver and intestine. The results demonstrated that CM exposure caused a significant increase in WBCs, lymphocytes, granulocytes, monocytes ALT, AST, ALP, and GGT, and total cholesterol and triglycerides levels accompanied by a decrease in HGB, HCT, RBCs and MCV, MCH, MCHC, HDL and glucose levels with no significant DNA damage in liver and blood. CM mixture induced severe pathological changes in small intestine and liver. Co-treatment of Res with CM improved hematological picture, lipid and glucose profiles also liver enzymes and decreased changes in the architecture of the liver and intestine.

Neuroprotective Effect of Vitamin D on Behavioral and Oxidative Parameters of Male and Female Adult Wistar Rats Exposed to Mancozeb (manganese/zinc ethylene bis-dithiocarbamate).

The constant exposure of rural workers to pesticides is a serious public health problem. Mancozeb (MZ) is a pesticide  linked to hormonal, behavioral, genetic, and neurodegenerative effects, mainly related to oxidative stress. Vitamin D is a promising molecule that acts as a protector against brain aging. This study aimed to evaluate the neuroprotective role of vitamin D in adult male and female Wistar rats exposed to MZ. Animals received 40 mg/kg of MZ i.p. and 12.5 µg/kg or 25 µg/kg vitamin D by gavage, twice a week, for 6 weeks. The concentration of manganese had a significant increase in the hippocampus of both sexes and in the striatum of females, unlike zinc, which did not show a significant increase. MZ poisoning led to mitochondrial changes in brain tissues and promoted anxiogenic effects, especially in females. Alterations in antioxidant enzymes, mainly in the catalase activity were observed in intoxicated rats. Taken together, our results showed that exposure to MZ leads to the accumulation of manganese in brain tissues, and the behavior and metabolic/oxidative impairment were different between the sexes. Furthermore, the administration of Vitamin D was effective in preventing the damage caused by the pesticide.

L-carnitine attenuates acoustic startle reflex dysfunction in adult male rats exposed to mancozeb.

The fungicide mancozeb increases oxygen-free radicals in the central nervous system. As an antioxidant, L-carnitine protects DNA and cell membranes from damage caused by oxygen-free radicals. The present study investigated how L-carnitine affected the acoustic startle response (ASR) in rats exposed to mancozeb. In this experimental study, male Wistar rats were gavaged orally with mancozeb (500, 1000, and 2000 mg/kg), L-carnitine (100, 200, and 400 mg/kg), or L-carnitine (200 mg/kg) + mancozeb (500 mg/kg) three times in 1 week. In the sham group, saline (0.9%, 10 mL/kg) was gavaged at a volume equivalent to that of the drugs. The control group did not receive any treatment. The results showed that locomotor activity and the percentage of prepulse inhibition in the mancozeb groups decreased compared to the sham group while these parameters increased in the L-carnitine group (200 mg/kg) compared to sham rats. In conclusion, mancozeb may increase the risk factor for cognitive diseases such as schizophrenia in people exposed to it while pretreatment with L-carnitine can attenuate the toxic effect.