Development of a histopathology scoring system for the pulmonary complications of organophosphorus insecticide poisoning in a pig model

Abstract

Organophosphorus (OP) insecticide self-poisoning causes over 100,000 global deaths annually. Around a third of patients are intubated and up to half of these can die. Post-mortem analysis of OP poisoned patients' lungs reveals consolidation, edema and hemorrhage, suggesting that direct or indirect lung damage may contribute to mortality. The lung injury caused by these formulated agricultural preparations is poorly characterised in humans, and a valid histopathology scoring system is needed in a relevant animal model to further investigate the disease and potential treatments. We conducted two pilot studies in anesthetized minipigs, which are commonly used for toxicological studies. In the first, pigs were given 2.5 mL/kg of either OP (n = 4) or saline (n = 2) by gavage and compared with positive controls (iv oleic acid n = 2). The second study simulated ingestion followed by gastric content aspiration: mixtures of OP (n = 3) or saline (n = 2) (0.63-0.71mL/kg) were placed in the stomach, and then small volumes of the gastric content were placed in the lung. At post-mortem examination, lungs were removed and inflation-fixed with 10% neutral buffered formalin. Samples (n = 62) were taken from cranial and caudal regions of both lungs. Two experienced lung histopathologists separately scored these samples using 8 proposed features of damage and their scores related (Kendall rank order). Two elements had small and inconsistent scores. When these were removed, the correlation increased from 0.74 to 0.78. Eight months later, a subset of samples (n = 35) was re-scored using the modified system by one of the previous histopathologists, with a correlation of 0.88. We have developed a reproducible pulmonary histopathology scoring system for OP poisoning in pigs which will assist future toxicological research and improve understanding and treatment of human OP poisoning.

Lung injury caused by aspiration of organophosphorus insecticide and gastric contents in pigs

“…Sampling of cranial and caudal regions of both right (directly injured) and left (indirectly injured) lungs was performed post-mortem (see online supplement) for each animal to assess the severity of regional lung injury [ 26 ].…”

An Overview of the Biochemical and Histopathological Effects of Insecticides

“…Pesticides have been widely used from past to present so that food production in the world is not affected by external factors. The most common use in the world is seen in the United States, and almost 15 billion dollars are spent annually for the pesticides [62,63] and the most common of them is the herbicide glyphosate [62,64]. Besides their use for sectoral beneficial results, they cause many metabolic disorders and lead to even death, especially due to their intake and absorption into the living body in various ways.…”

“…Besides their use for sectoral beneficial results, they cause many metabolic disorders and lead to even death, especially due to their intake and absorption into the living body in various ways. OP compounds [65] are responsible for half of the deaths by inhibiting the acetylcholinesterase enzyme (AChE) in the central and autonomic nervous systems, lungs and neuromuscular junctions [62,66,67]. AChE inhibition increases cholinergic activity in both the central and peripheral nervous systems.…”

“…AChE inhibition increases cholinergic activity in both the central and peripheral nervous systems. Loss of consciousness, diarrhea, bronchospasm, paralysis and vomiting are the most typical symptoms of poisoning [62,68], and death can occur as a result of respiratory failure [69,70]. The toxicity of the substances taken into the organism, its chemical Insecticides structure, the human resources involved in the poisoning event and the quality of the institution providing medical support affect the mortality rate [71].…”

High Prevalence of Recombinant Porcine Endogenous Retroviruses (PERV-A/Cs) in Minipigs: A Review on Origin and Presence

“…Worldwide several breeds of minipigs (also called miniature swine or micropigs) have been established ( Table 1 ) and most of these minipigs are used in biomedical research and development, only some of them are favored as pets. The main fields in biomedicine using minipigs are basic research [ 1 ], experimental surgery [ 2 ], pulmonology [ 3 ], cardiology [ 4 ], transplantation [ 5 ], toxicology [ 6 ], pharmacology and safety assessment of new drugs [ 7 ], orthopedic procedures [ 8 ], aging studies [ 9 ], medical devices [ 10 ], food additives [ 11 ] and agrochemicals [ 12 ]. The skin, gastrointestinal tract, cardiovascular system, kidney and bladder are very similar to humans in terms of anatomy and function, e.g., their liver metabolism is similar to humans for most cytochrome P450 (CYP) isoenzymes [ 13 ].…”