Ultrastructural evidence of pulmonary capillary endothelial damage from paraquat

Dearden, Lyle C.; Fairshter, Ronald D.; Morrison, John T.; Wilson, Archie F.; M, Brundage

doi:10.1016/0300-483x(82)90003-8

Cited by 27 publications

(8 citation statements)

References 19 publications

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“…Paraquat toxicity is most severe in the lungs and leads to an acute alveolitis. Further effects include diffuse alveolar collapse, vascular congestion and adherence of activated platelets and polymorphonuclear leucocytes to the vascular endothelium [43–45]. In the lung, as in most tissues, paraquat toxicity leads to apoptosis of affected cells [46–49].…”

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confidence: 99%

Medical management of paraquat ingestion

Gawarammana¹,

Buckley²

2011

Brit J Clinical Pharma

409

413

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Poisoning by paraquat herbicide is a major medical problem in parts of Asia while sporadic cases occur elsewhere. The very high case fatality of paraquat is due to inherent toxicity and lack of effective treatments. We conducted a systematic search for human studies that report toxicokinetics, mechanisms, clinical features, prognosis and treatment. Paraquat is rapidly but incompletely absorbed and then largely eliminated unchanged in urine within 12-24 h. Clinical features are largely due to intracellular effects. Paraquat generates reactive oxygen species which cause cellular damage via lipid peroxidation, activation of NF-kB, mitochondrial damage and apoptosis in many organs. Kinetics of distribution into these target tissues can be described by a two-compartment model. Paraquat is actively taken up against a concentration gradient into lung tissue leading to pneumonitis and lung fibrosis. Paraquat also causes renal and liver injury. Plasma paraquat concentrations, urine and plasma dithionite tests and clinical features provide a good guide to prognosis. Activated charcoal and Fuller's earth are routinely given to minimize further absorption. Gastric lavage should not be performed. Elimination methods such as haemodialysis and haemoperfusion are unlikely to change the clinical course. Immunosuppression with dexamethasone, cyclophosphamide and methylprednisolone is widely practised, but evidence for efficacy is very weak. Antioxidants such as acetylcysteine and salicylate might be beneficial through free radical scavenging, anti-inflammatory and NF-kB inhibitory actions. However, there are no published human trials. The case fatality is very high in all centres despite large variations in treatment.

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confidence: 99%

Medical management of paraquat ingestion

Gawarammana¹,

Buckley²

2011

Brit J Clinical Pharma

409

413

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“…Cumulating evidence indicates that PQ impacts endothelial cell permeability [31], and causes rupture of the basement membrane of pulmonary vasculature in rats [9,32]; in contrast,…”

Section: Discussionmentioning

confidence: 99%

Identification of apoptosis and macrophage migration events in paraquat-induced oxidative stress using a zebrafish model

Wang

Liu

et al. 2016

Life Sciences

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“…In the past few decades, many studies have shown that acute PQ poisoning can lead to injury and dysfunction in the liver, kidney, ear, and other important organs . Moreover, many studies have shown that the severity of lung and vascular endothelial injury, as well as the inflammatory reaction, are time‐ and dose‐dependent with respect to PQ poisoning . Some studies using animal models suggest that PQ poisoning can cause coagulation dysfunction, although there is a lack of detailed research on the effects and extent of PQ toxicity with respect to human coagulation function.…”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15] Moreover, many studies have shown that the severity of lung and vascular endothelial injury, as well as the inflammatory reaction, are time-and dose-dependent with respect to PQ poisoning. [16][17][18][19] Some studies using animal models suggest that PQ poisoning can cause coagulation dysfunction, although there is a lack of detailed research on the effects and extent of PQ toxicity with respect to human coagulation function. While we already know that acute PQ poisoning can cause human blood coagulation dysfunction, the possible relationship between the ingestion dose and the severity of coagulation dysfunction are still unclear.…”

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confidence: 99%