The organophosphorus pesticide dimethoate decreases cell viability and induces changes in different biochemical parameters of rat pancreatic stellate cells

Martínez-Morcillo, Salomé; Pérez-López, Marcos; Soler-Rodríguez, Francisco; González, Antonio

doi:10.1016/j.tiv.2018.09.011

Cited by 12 publications

(6 citation statements)

References 41 publications

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“…Because the increase in [Ca 2+ ] i was also observed in the absence of Ca 2+ in the extracellular medium, Ca 2+ mobilization must derive from an intracellular source, most probably the endoplasmic reticulum. In this line, the additional incubation of cells subjected to hypoxia with the SERCA inhibitor thapsigargin evoked a rather small Ca 2+ response, which was smaller than that induced by the inhibitor when it is applied alone (Martinez‐Morcillo et al., 2019). This fact reflects that the intracellular Ca 2+ stores had been depleted by the treatment of cells under hypoxia and, moreover, suggests that the source for Ca 2+ mobilization under hypoxia is the ER.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic stellate cells exhibit adaptation to oxidative stress evoked by hypoxia

Estarás

Martínez-Morcillo

García

et al. 2020

Biology of the Cell

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Background information. Pancreatic stellate cells play a key role in the fibrosis that develops in diseases such as pancreatic cancer. In the growing tumour, a hypoxia condition develops under which cancer cells are able to proliferate. The growth of fibrotic tissue contributes to hypoxia. In this study, the effect of hypoxia (1% O 2) on pancreatic stellate cells physiology was investigated. Changes in intracellular free-Ca 2+ concentration, mitochondrial free-Ca 2+ concentration and mitochondrial membrane potential were studied by fluorescence techniques. The status of enzymes responsible for the cellular oxidative state was analyzed by quantitative reverse transcriptionpolymerase chain reaction, high-performance liquid chromatography, spectrophotometric and fluorimetric methods and by Western blotting analysis. Cell viability and proliferation were studied by crystal violet test, 5-bromo-2deoxyuridine cell proliferation test and Western blotting analysis. Finally, cell migration was studied employing the wound healing assay. Results. Hypoxia induced an increase in intracellular and mitochondrial free-Ca 2+ concentration, whereas mitochondrial membrane potential was decreased. An increase in mitochondrial reactive oxygen species production was observed. Additionally, an increase in the oxidation of proteins and lipids was detected. Moreover, cellular total antioxidant capacity was decreased. Increases in the expression of superoxide dismutase 1 and 2 were observed and superoxide dismutase activity was augmented. Hypoxia evoked a decrease in the oxidized/reduced glutathione ratio. An increase in the phosphorylation of nuclear factor erythroid 2-related factor and in expression of the antioxidant enzymes catalytic subunit of glutamate-cysteine ligase, catalase, NAD(P)H-quinone oxidoreductase 1 and heme oxygenase-1 were detected. The expression of cyclin A was decreased, whereas expression of cyclin D and the content of 5-bromo-2-deoxyuridine were increased. This was accompanied by an increase in cell viability. The phosphorylation state of c-Jun NH 2-terminal kinase was increased, whereas that of p44/42 and p38 was decreased. Finally, cells subjected to hypoxia maintained migration ability. Conclusions and Significance. Hypoxia creates pro-oxidant conditions in pancreatic stellate cells to which cells adapt and leads to increased viability and proliferation.

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Section: Discussionmentioning

confidence: 99%

Pancreatic stellate cells exhibit adaptation to oxidative stress evoked by hypoxia

Estarás

Martínez-Morcillo

García

et al. 2020

Biology of the Cell

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“…The highest dilution of DMSO used in the treatments was <0.05% (v/v). At this concentration, no observable toxic effects to the cells have been observed (Martínez‐Morcillo, Pérez‐López, Soler‐Rodríguez, & González, 2019). Nonstimulated cells, i.e., those cells that were not subjected to luzindole or Tps, were incubated in the presence of the vehicle and were used to compare the effects of the drugs.…”

Section: Methodsmentioning

confidence: 99%

“…Handling of animals, methods and experimental protocols applied were approved by, and performed in accordance with, the relevant A stock concentration of luzindole was prepared in DMSO, from which the stimuli used in the study were prepared. The highest dilution of DMSO used in the treatments was <0.05% & González, 2019). Nonstimulated cells, i.e., those cells that were not subjected to luzindole or Tps, were incubated in the presence of the vehicle and were used to compare the effects of the drugs.…”

Section: Cell Cultures and Chemicalsmentioning

confidence: 99%

The melatonin receptor antagonist luzindole induces the activation of cellular stress responses and decreases viability of rat pancreatic stellate cells

Estarás

Marchena

Fernandez–Bermejo

et al. 2020

J of Applied Toxicology

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In this study, we have examined the effects of luzindole, a melatonin receptor-antagonist, on cultured pancreatic stellate cells. Intracellular free-Ca 2+ concentration, production of reactive oxygen species (ROS), activation of mitogen-activated protein kinases (MAPK), endoplasmic reticulum stress and cell viability were analyzed. Stimulation of cells with the luzindole (1, 5, 10 and 50 μM) evoked a slow and progressive increase in intracellular free Ca 2+ ([Ca 2+ ] i) towards a plateau. The effect of the compound on Ca 2+ mobilization depended on the concentration used. Incubation of cells with the sarcoendoplasmic reticulum Ca 2+-ATPase inhibitor thapsigargin (1 μM), in the absence of Ca 2+ in the extracellular medium, induced a transient increase in [Ca 2 + ] i. In the presence of thapsigargin, the addition of luzindole to the cells failed to induce further mobilization of Ca 2+. Luzindole induced a concentration-dependent increase in ROS generation, both in the cytosol and in the mitochondria. This effect was smaller in the absence of extracellular Ca 2+. In the presence of luzindole the phosphorylation of p44/42 and p38 MAPKs was increased, whereas no changes in the phosphorylation of JNK could be noted. Moreover, the detection of the endoplasmic reticulum stress-sensor BiP was increased in the presence of luzindole. Finally, viability was decreased in cells treated with luzindole. Because cellular membrane receptors for melatonin have not been detected in pancreatic stellate cells, we conclude that luzindole could exert direct effects that are not mediated through its action on melatonin membrane receptors.

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“…Dimethoate, an organophosphorus insecticide, is widely used for controlling a wide range of insects. However, many studies have shown adverse effects on mammalian [6][7][8] . Several studies have documented that the carcinogenicity [9] and developmental toxicity [10,11] of dimethoate which can lead to a reduction in plasma cholinesterase [12] .…”

Section: Introductionmentioning

confidence: 99%

A new approach for reducing pollutants level: a longitudinal cohort study of physical exercises in young people

Gao

et al. 2022

BMC Public Health

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Background The present study aimed to evaluate the elimination of three common pollutants (dimethoate, benzo(a)pyrene (BaP) and bisphenol A (BPA) by different physical exercises and to assess the possible factors which could affect the pollutants elimination. Methods A total of 200 individuals who chose different kinds of exercises in accordance to their own wish were recruited. The levels of urinary pollutants were measured using β-glucuronidase hydrolysis followed by a high-performance liquid chromatography tandem mass spectrometry-based method. Results Totally, the levels of dimethoate, BaP and BPA were reduced after physical exercises. However, the elimination of BaP in male was higher than that in female but the elimination of BPA in female was higher than that in male. Multivariate logistic regression showed that the degree of heart rate (HR) change was a protective factor affecting the improvement effect of dimethoate, BaP and BPA while BMI (body mass index) was a risk factor. Nevertheless, sex was a risk factor affecting the improvement of dimethoate and BaP but had a lower efficacy on BPA improvement. Conclusion The present findings indicate that physical exercises can be considered as a novel approach to eliminate pollutants level in human body and can also give suggestions for choosing specific physical exercises to male and female individuals. Moreover, those who are with higher BMI need to lose weight before eliminating pollutant level through physical exercises.

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The organophosphorus pesticide dimethoate decreases cell viability and induces changes in different biochemical parameters of rat pancreatic stellate cells

Cited by 12 publications

References 41 publications

Pancreatic stellate cells exhibit adaptation to oxidative stress evoked by hypoxia

Pancreatic stellate cells exhibit adaptation to oxidative stress evoked by hypoxia

The melatonin receptor antagonist luzindole induces the activation of cellular stress responses and decreases viability of rat pancreatic stellate cells

A new approach for reducing pollutants level: a longitudinal cohort study of physical exercises in young people

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