The organophosphorus pesticide dimethoate decreases cell viability and induces changes in different biochemical parameters of rat pancreatic stellate cells. (February 2019)

• Record Type: Journal Article
• Authors: Martínez-Morcillo, Salomé; Pérez-López, Marcos; Soler-Rodríguez, Francisco; González, Antonio
• Is Part Of: Toxicology in vitro. Volume 54(2019)
• Page Start: 89
• Page End: 97
• Publication Date: 2019-02
• Subjects: Calcium -- Dimethoate -- Esterase activity -- Organophosphorus insecticide -- Pancreatic stellate cells; ACh Acetylcholine -- AChE Acetylcholinesterase -- BChE Butyrylcholinesterase -- [Ca2+]i Intracellular free Ca2+ concentration -- CbEs Carboxylesterases -- ChE Cholinesterases -- ATCI Acetylthiocholine iodide -- BTCI Butyrylthiocholine iodide -- α-NA α-Naphthyl acetate -- EGTA Ethylene glycol-bis(2-aminoethylether)-N, N, N´N´-tetraacetic acid -- ER Endoplasmic reticulum -- Fura-2/AM Fura-2 acetoxymethyl ester -- OPs Organophosphorous compounds -- PSCs Pancreatic stellate cells -- SERCA Sarcoendoplasmic reticulum Ca2+-ATPase -- Tps Thapsigargin; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2018.09.011
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: In the present study we employed cultured pancreatic stellate cells to study the effect of the organophosphorus insecticide dimethoate on pancreatic cell physiology. Esterase activity, cell viability, reactive oxygen species generation and Ca 2+ mobilization were examined. Our results show that dimethoate (0.1, 1 and 10 μM) induced a concentration-dependent inhibition of cholinesterase enzymatic activity at all concentrations tested. A drop in carboxylesterase activity was noted in the presence of 10 μM dimethoate. In the presence of the pesticide a decrease in cell viability was detected. The clearer effect could be observed when the cells had been incubated during 96 h in the presence of dimethoate. The pesticide induced a slight but statistically significant increase in the production of reactive oxygen species in the mitochondria. Incubation of cells with dimethoate, in the presence of Ca 2+ in the extracellular medium, led to a slow and progressive increase in [Ca 2+ ]c towards an elevated value over the prestimulation level. A similar behavior was observed in the absence of extracellular Ca 2+, indicating that dimethoate releases Ca 2+ from the intracellular stores. Our results suggest that dimethoate might alter intracellular pathways that are critical for pancreatic physiology, creating a situation potentially leading to dysfunction in the exocrine pancreas. Graphical abstract: Highlights: Dimethoate inhibited certain esterases enzymatic activity in PSCs. Cell viability was reduced in the presence of the pesticide. Dimethoate induced a slight increase in reactive oxygen species production. In the presence of dimethoate a slow and progressive increase in [Ca 2+ ]c was observed.