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

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 Ca2+ 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 Ca2+ in the extracellular medium, led to a slow and progressive increase in [Ca2+]c towards an elevated value over the prestimulation level. A similar behavior was observed in the absence of extracellular Ca2+, indicating that dimethoate releases Ca2+ 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.