Molecular Mechanisms of Acute Organophosphate Nephrotoxicity

Abstract

Organophosphates (OPs) are toxic chemicals produced by an esterification process and some other routes. They are the main components of herbicides, pesticides, and insecticides and are also widely used in the production of plastics and solvents. Acute or chronic exposure to OPs can manifest in various levels of toxicity to humans, animals, plants, and insects. OPs containing insecticides were widely used in many countries during the 20th century, and some of them continue to be used today. In particular, 36 OPs have been registered in the USA, and all of them have the potential to cause acute and sub-acute toxicity. Renal damage and impairment of kidney function after exposure to OPs, accompanied by the development of clinical manifestations of poisoning back in the early 1990s of the last century, was considered a rare manifestation of their toxicity. However, since the beginning of the 21st century, nephrotoxicity of OPs as a manifestation of delayed toxicity is the subject of greater attention of researchers. In this article, we present a modern view on the molecular pathophysiological mechanisms of acute nephrotoxicity of organophosphate compounds.

The Hematological and Biochemical Effects from Pesticide Exposure on Thai Vegetable Farmers

“…This significant difference was in agreement with previous findings for pesticide-exposed individuals, in which associations with lower eGFR were observed for organophosphates and carbamates, as well as herbicides such as atrazine and glyphosate [ 33 , 34 , 35 , 36 ]. Organophosphate exposure may alter the glomeruli, as well as the proximal and distal tubules [ 46 , 47 ]. Neonicotinoids have been identified as a possible risk factor for renal tubular dysfunction [ 48 ].…”

Organophosphorus Poisoning: Acute Respiratory Distress Syndrome (ARDS) and Cardiac Failure as Cause of Death in Hospitalized Patients

“…Macroscopic and microscopic autopsy findings in the lungs of those who died within the first 24 h after hospitalization were characterized by interstitial edema and hemorrhage in lungs [ 70 ] and tubular degeneration in the kidney (acute tubular necrosis); also, in those who died later after OP poisoning [ 75 , 76 , 77 , 78 , 79 , 80 ], the findings mostly resemble those observed in people who died of acute respiratory distress syndrome (ARDS) [ 81 , 82 ] of different causes, including viral infections of the upper respiratory tract [ 83 , 84 , 85 , 86 ] and also paraquat intoxication [ 87 ]. Similar histopathological (microscopic) changes can be induced in minipigs by bronchoscopic instillation of gastric juice containing OP (40% dimethoate 0.5 mL/kg) into the lung [ 88 ], simulating aspiration of gastric content, as may happen after ingestion of the insecticide mostly with suicidal intention.…”

“…Autopsies are seldom performed in patients who died because of AOPP, and in most cases, it is related to the search for the toxic agent [ 77 , 78 , 79 , 80 , 81 , 82 ] and less to mechanisms that lead to death such as cardiac arrest, especially in persons of young age.…”

Types and Toxicity Levels of Pesticides: A Study of an Agricultural Area in Brebes Regency

“…Organophosphate exposure also affects insulin resistance, neurobehavioral function, blood profile, oxidative stress, and metabolism of carbohydrates, fats, and proteins in the cytoplasm/ mitochondria/ peroxisomes (49)(50)(51)(52)(53)(54). The toxic effects of OPs on nephrons through molecular mechanisms include binding of albumin to the OPs, the interaction of OPs complex and serum albumin and their metabolites with kidney tissues and cells, and the protection of albumin against OPs (55). Chronic organophosphate exposure results in higher pancreatic insulin secretion, causing pancreatic hypertrophy.…”