Cytotoxic, genotoxic and biochemical markers of insecticide toxicity evaluated in human peripheral blood lymphocytes and an HepG2 cell line

Želježić, Davor; Mladinić, Marin; Žunec, Suzana; Vrdoljak, Ana Lucić; Kašuba, Vilena; Tariba, Blanka; Živković, Tanja; Marjanović, Ana Marija; Pavičić, Ivan; Milić, Mirta; Rozgaj, Ružica; Kopjar, Nevenka

doi:10.1016/j.fct.2016.07.036

Cited by 48 publications

(15 citation statements)

References 85 publications

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“…It can be argued that we should have tested higher concentrations of the neonicotinoids by dissolving them in DMSO even if we did not see any cytotoxic effects in the pilot studies, but it shall be noted that the lowest concentration of neonicotinoide used without S9 in our comet assays (0.5 μM) is a reasonable biologically relevant concentration, at least according to Zeljezic et al (2016) who estimated that the concentration of imidacloprid in human serum in a male human weighing 65 kg would be around 0.1 μg/ml (0.4 μM) at an estimated acceptable daily intake. The highest concentration used in the evaluation of potential DNA damage was set to 50 μM as it was considered well above realistic serum levels and could be achieved from stock solutions using on growth medium as the solvent.…”

Section: Discussionmentioning

confidence: 99%

“…While the toxicity of neonicotinoids in honeybees has been investigated extensively, studies on material of human origin seem sparse, especially when it comes to nitenpyram. Whereas there are some in vitro studies of the cytotoxicity of imidacloprid in human cells (Al-Sarar et al 2015;Bianchi et al 2015;Calderon-Segura et al 2012;Senyildiz et al 2018;Zeljezic et al 2016)-no similar studies of nitenpyram were found in our literature search. A similar picture emerges when it comes to genotoxicity studies of imidacloprid and nitenpyram.…”

Section: Introductionmentioning

confidence: 88%

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Evaluation of Potential DNA-Damaging Effects of Nitenpyram and Imidacloprid in Human U937-Cells Using a New Statistical Approach to Analyse Comet Data

et al. 2019

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Even if the two neonicotinoids nitenpyram and imidacloprid have been considered safe for humans, their potential genotoxicity still remains a matter of discussion. The DNA-damaging effects of these two compounds were therefore evaluated in a lymphoma cell line of human origin (U-937) using the comet assay after 3-h exposure to up to 50 μM, with or without metabolic activation using S9 from human liver. The comet data were analysed using a traditional one-way ANOVA after pooling the data on cellular level, and a new alternative approach we have called Uppsala Comet Data Analysis Strategy (UCDAS). UCDAS is a proportional odds model tailored to continuous outcomes, taking the number of pooled cultures, slides and cells into consideration in the same analysis. To the best of our knowledge, the UCDAS approach when analysing comet data has never been presented before. Without metabolic activation, no increase in DNA damage was observed in the neonicotinoide-exposed cells. Nitenpyram was also without DNA-damaging effects when S9 was added. However, in the presence of S9, imidacloprid was found to increase the level of DNA damage. Whereas the ANOVA showed an increase (P < 0.001) both at 5 and 50 μM, UCDAS showed an increase only at the lowest concentration (P < 0.001). Based on these findings, the two neonicotinoids seem to be of little concern when it comes to their potential genotoxicity. However, since the U-937 cells were rather resistant to our positive controls, they may not be the best cells to use when evaluating potential genotoxicity of chemicals.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%

Evaluation of Potential DNA-Damaging Effects of Nitenpyram and Imidacloprid in Human U937-Cells Using a New Statistical Approach to Analyse Comet Data

et al. 2019

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“…Therefore, we may speculate that OP phosphorylate proteins/low molecular antioxidants, creating a pro‐oxidative status. On the other hand, several studies have demonstrated that OP binds to DNA (Ivanović, Rapić, & Bošković, ; Želježić et al, ). DNA damage activates response machinery, including p53, NF‐κB and MAPK pathways, which regulate genes involved in ROS metabolism as well as Ca 2+ homeostasis and apoptosis (Bonora, Giorgi, & Pinton, ; Lee, Lim, Park, Park, & Koh, ; Li & Karin, ; Pejchal et al, ; Pejchal, Osterreicher, Kassa, Tichý, & Mokrý, ; RamaRao & Bhattacharya, ).…”

Section: Oxidative Stressmentioning

confidence: 99%

Oxidative stress in organophosphate poisoning: role of standard antidotal therapy

Váňová

Pejchal

Herman

et al. 2018

J of Applied Toxicology

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Despite the main mechanism of organophosphate (OP) toxicity through inhibition of acetylcholinesterase (AChE) being well known over the years, some chronic adverse health effects indicate the involvement of additional pathways. Oxidative stress is among the most intensively studied. Overstimulation of cholinergic and glutamatergic nervous system is followed by intensified generation of reactive species and oxidative damage in many tissues. In this review, the role of oxidative stress in pathophysiology of OP poisoning and the influence of commonly used medical interventions on its levels are discussed. Current standardized therapy of OP intoxications comprises live-saving administration of the anticholinergic drug atropine accompanied by oxime AChE reactivator and diazepam. The capability of these antidotes to ameliorate OP-induced oxidative stress varies between both therapeutic groups and individual medications within the drug class. Regarding oxidative stress, atropine does not seem to have a significant effect on oxidative stress parameters in OP poisoning. In a case of AChE reactivators, pro-oxidative and antioxidative properties could be found. It is assumed that the ability of oximes to trigger oxidative stress is rather associated with their chemical structure than reactivation efficacy. The data indicating the potency of diazepam in preventing OP-induced oxidative stress are not available. Based on current knowledge on the mechanism of OP-mediated oxidative stress, alternative approaches (including antioxidants or multifunctional drugs) in therapy of OP poisoning are under consideration.

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“…In vitro studies reported that imidacloprid disrupted the glutathione redox cycle by affecting its components glutathione reductase (gR), glutathione peroxidase (gPX), and glutathione-Stransferase (gST) in Chinese hamster ovary cells (CHO K1 ) (33) and to activate the ERK cascade via nAChRs and intracellular calcium mobilisation in mouse N1E-115 neuroblastoma cells (38), which may affect the functioning of the neurons. The effects of imidacloprid were also studied in human lymphocytes and Hepg2 cells after four-and 24-hour exposure to concentrations corresponding to the acceptable daily intake (ADI), residential exposure level (REL), and occupational exposure level (OEL) (39). The results showed that the applied imidacloprid concentrations did not trigger significant lipid peroxidation nor did they affect the total antioxidative capacity of lymphocytes or Hepg2 cells (39).…”

Section: Neonicotinoidsmentioning

confidence: 99%

“…The effects of imidacloprid were also studied in human lymphocytes and Hepg2 cells after four-and 24-hour exposure to concentrations corresponding to the acceptable daily intake (ADI), residential exposure level (REL), and occupational exposure level (OEL) (39). The results showed that the applied imidacloprid concentrations did not trigger significant lipid peroxidation nor did they affect the total antioxidative capacity of lymphocytes or Hepg2 cells (39).…”

Section: Neonicotinoidsmentioning

confidence: 99%

Redox imbalance caused by pesticides: a review of OPENTOX-related research

Čermak

Pavičić

Želježić

2018

Archives of Industrial Hygiene and Toxicology

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Pesticides are a highly diverse group of compounds and the most important chemical stressors in the environment. Mechanisms that could explain pesticide toxicity are constantly being studied and their interactions at the cellular level are often observed in well-controlled in vitro studies. Several pesticide groups have been found to impair the redox balance in the cell, but the mechanisms leading to oxidative stress for certain pesticides are only partly understood. As our scientific project "Organic pollutants in environment - markers and biomarkers of toxicity (OPENTOX)" is dedicated to studying toxic effects of selected insecticides and herbicides, this review is focused on reporting the knowledge regarding oxidative stress-related phenomena at the cellular level. We wanted to single out the most important facts relevant to the evaluation of our own findings from studies conducted on in vitro cell models.

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Cytotoxic, genotoxic and biochemical markers of insecticide toxicity evaluated in human peripheral blood lymphocytes and an HepG2 cell line

Cited by 48 publications

References 85 publications

Evaluation of Potential DNA-Damaging Effects of Nitenpyram and Imidacloprid in Human U937-Cells Using a New Statistical Approach to Analyse Comet Data

Evaluation of Potential DNA-Damaging Effects of Nitenpyram and Imidacloprid in Human U937-Cells Using a New Statistical Approach to Analyse Comet Data

Oxidative stress in organophosphate poisoning: role of standard antidotal therapy

Redox imbalance caused by pesticides: a review of OPENTOX-related research

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