Paraquat Poisonings: Mechanisms of Lung Toxicity, Clinical Features, and Treatment

Abstract

R. J. Dinis-Oliveiraabc, J. A. Duarted, A. Sánchez-Navarroe, F. Remiãoa, M. L. Bastosa & F. Carvalhoaa REQUIMTE, Departamento de Toxicologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugalb Departamento de Análises Clínicas e Saúde Pública, Cooperative de Ensino Superior, Politécnico e Universitário, CRL, Vila Nova de FamalicãoPortugalc Instituto Nacional de Medicina Legal – Delegação Norte, Faculdade de Medicina, Universidade do Porto, Porto, Portugald CIAFEL, Faculdade de Desporto, Universidade do Porto, Porto, Portugale Departamento de Farmacia y Tecnología Farmacélutica, Facultad de Farmacia, Universidad de Salamanca, Salamanca, EspañaREQUIMTE, Departamento de Toxicologia, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4099-030, Porto, PortugalREQUIMTE, Departamento de Toxicologia, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4099-030, Porto, PortugalParaquat dichloride (methyl viologen; PQ) is an effective and widely used herbicide that has a proven safety record when appropriately applied to eliminate weeds. However, over the last decades, there have been numerous fatalities, mainly caused by accidental or voluntary ingestion. PQ poisoning is an extremely frustrating condition to manage clinically, due to the elevated morbidity and mortality observed so far and due to the lack of effective treatments to be used in humans. PQ mainly accumulates in the lung (pulmonary concentrations can be 6 to 10 times higher than those in the plasma), where it is retained even when blood levels start to decrease. The pulmonary effects can be explained by the participation of the polyamine transport system abundantly expressed in the membrane of alveolar cells type I, II, and Clara cells. Further downstream at the toxicodynamic level, the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. With this review we aimed to collect and describe the most pertinent and significant findings published in established scientific publications since the discovery of PQ, focusing on the most recent developments related to PQ lung toxicity and their relevance to the treatment of human poisonings. Considerable space is also dedicated to techniques for prognosis prediction, since these could allow development of rigorous clinical protocols that may produce comparable data for the evaluation of proposed therapies.