The herbicide paraquat-induced molecular mechanisms in the development of acute lung injury and lung fibrosis

Abstract

The herbicide paraquat (PQ; 1,1’-dimethyl-4,4’-bipyridylium dichloride) is a highly toxic organic heterocyclic herbicide that has been widely used in agricultural settings. Since its commercial introduction in the early 1960s, numerous cases of fatal PQ poisonings attributed to accidental and/or intentional ingestion of PQ concentrated formulations have been reported. The clinical manifestations of the respiratory system during the acute phase of PQ poisoning mainly include acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), followed by pulmonary fibrosis in a later phase. The focus of this review is to summarize the most recent publications related to PQ-induced lung toxicity as well as the underlying molecular mechanisms for PQ-mediated pathologic processes. Growing sets of data from in vitro and in vivo models have demonstrated the involvement of the PQ in regulating lung oxidative stress, inflammatory response, epigenetics, apoptosis, autophagy, and the progression of lung fibrosis. The article also summarizes novel therapeutic avenues based on a literature review, which can be explored as potential means to combat PQ-induced lung toxicity. Finally, we also presented clinical studies on the association of PQ exposure with the incidence of lung injury and pulmonary fibrosis.

Keywords:

• Acute lung injury
• inflammation
• paraquat
• pulmonary fibrosis
• signaling pathways

Acknowledgments

The authors gratefully acknowledge Dr Roger O. McClellan and anonymous reviewers for reviewing the manuscript and for all their comments and critiques. The comprehensive review process helped to improve the final manuscript. The authors also wish to thank Dr Sathish Venkatachalem, Department of Pharmaceutical Sciences, North Dakota State University, Fargo, USA and Dr Rajesh K. Thimmulappa, Center for Excellence in Molecular Biology & Regenerative Medicine, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, India for their assistance in reviewing the manuscript and providing additional feedback. The authors acknowledge Sci-Edit Publications, India for performing language corrections on service charge basis. Also, the authors acknowledge Ms. Nandhine Rajasekar, Research Scholar of Department of Biotechnology, Anna University, BIT-Campus, Tiruchirappalli, India for her assistance in preparing tables and in the formatting of citations. She was not considered for authorship as she was only involved in the preparation of the manuscript as described above, and she did not participate in the discussions of the contents of the manuscript, nor in developing the conclusions reached by the authors regarding those contents.

Declaration of interest

The authors report no conflict of interest. The author’s affiliation is as shown on the cover page. The authors participated in the development of the paper as individual professionals and have sole responsibility for the writing and content of the paper. Neither of the authors has been involved in the last 5 years with regulatory or legal proceedings related to the contents of the paper and neither has received funding in the last 5 years in support of the preparation of the paper.