PROBIEN   20416
INSTITUTO DE INVESTIGACION Y DESARROLLO EN INGENIERIA DE PROCESOS, BIOTECNOLOGIA Y ENERGIAS ALTERNATIVAS
Unidad Ejecutora - UE
capítulos de libros
Título:
Primary and secondary targets of action-response to anticholinesterase pesticide exposure in fish: trends in underlying molecular mechanisms
Autor/es:
FERRARI A; PECHEN DE D'ANGELO A.M.; VENTURINO A
Libro:
Pesticide Research Trends
Editorial:
Nova Publishers
Referencias:
Lugar: New York; Año: 2008;
Resumen:
Organophosphorus (OP) and carbamate (CB) pesticides are known to inhibit the enzyme acetylcholinesterase (AChE) in vertebrates and invertebrates, leading to the accumulation of the neurotransmitter acetylcholine and the subsequent over-stimulation of cholinergic receptors. In fish, the effects of these compounds on AChE and different esterases have been extensively studied. In most cases, OP are more effective and persistent AChE inhibitors than CB, due to both differences in reactivation rates and aging process. Brain AChE inhibition has been proposed as the major determinant of OP and CB acute toxicity in mammals and other organisms. However, many fish species are able to survive high percentages of brain AChE inhibition, thus there are other determinant targets of anticholinesterase pesticides acute toxicity such as muscular ChE. The protective action of carboxylesterases seems to be also variable among fish in relation to other organisms. Secondary targets are currently studied in addition to esterases, in order to elucidate molecular mechanisms modulating the action of OP and CB and the cellular response to exposure. In fish, different OP and CB have been reported to induce oxidative stress and affect glutathione, glutathione-related enzymes, and other antioxidant enzymes such as catalase and superoxide dismutase. It is known that reactive oxygen species modulate cell signaling and transcription factor activity, affecting gene expression. These effects related to pesticide exposure have been mainly reported in mammalian cell lines, whereas research on fish is scarce. Some OP and CB induce glutathione-S transferase enzymes in fish, and this induction may be related to nuclear factor Nrf-2 binding to the antioxidant response element (ARE). In addition, some CB are weak agonists of the aryl hydrocarbon receptor (AhR), activating the xenobiotic response element (XRE) and inducing cytochrome P450 1A (CYP1A). The differential modulation of gene expression in OP and CB exposures may be crucial to cell fate towards apoptosis or proliferation and sublethal/ chronic toxicity. Thus, the study of these molecular targets in fish is highly relevant for the clarification of molecular mechanisms of toxicity and the search of earlier and more sensitive biomarkers of effect and response.