Acceleration of Lipid Peroxidation in Human Paraquat Poisoning

Yasaka, Tatsuomi

doi:10.1001/archinte.1981.00340090065015

Cited by 38 publications

(8 citation statements)

References 12 publications

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“…Lipid peroxidation Electrophilic free radicals can extract hydrogen atoms from polyunsaturated fatty acids thus causing lipid peroxidation. In vitro, animal and human studies have demonstrated that paraquat can induce lipid peroxidation [25][26][27]. Widespread lipid peroxidation compromises cell membrane function and may trigger apoptosis.…”

Section: Secondary Effects Of Oxidative Stressmentioning

confidence: 99%

Medical management of paraquat ingestion

Gawarammana¹,

Buckley²

2011

Brit J Clinical Pharma

415

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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Section: Secondary Effects Of Oxidative Stressmentioning

confidence: 99%

Medical management of paraquat ingestion

Gawarammana¹,

Buckley²

2011

Brit J Clinical Pharma

415

413

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“…In the late phase of paraquat exposure, at more than 2 weeks, interstitial fibrosis and marked proliferation of alveolar macrophages were seen (Saunier et al 1982;Kihune et al 1990). In studies of fatal paraquat intoxication in humans, in which single doses but large amounts of paraquat were taken, lung injuries such as pulmonary edema, hemorrhage (death within 6 days), and fibrosis (death over 2 weeks) were observed besides enhanced lipid peroxidation, (Yasaka et al 1981(Yasaka et al , 1986Ishii et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Consecutive administration of paraquat to rats induces enhanced cholesterol peroxidation and lung injury

et al. 2003

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It is our hypothesis that as a consequence of increased oxidative stress, rats develop lung injury with increased cholesterol-derived hydroperoxides and oxysterols in lung after consecutive exposure of the rats to paraquat. To test this we administered 10 mg/kg of paraquat i.p. once or seven times (once a day) to Wistar rats. Rats were killed, and lung tissue was collected 24 h after the last paraquat injection. We found that in response to consecutive paraquat doses, there were significant increases in 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH and 7beta-OOH; P=0.01) as well as 7alpha- and 7beta-hydroxycholesterol (7alpha-OH and 7beta-OH; P=0.01), and 7-ketocholesterol (7-keto; P=0.03). In addition, pulmonary hemorrhage, thickening of alveolar septum, and inflammatory cell infiltration of macrophages were observed. This is the first report showing enhanced cholesterol peroxidation and lung injury of rats due to consecutive doses of paraquat.

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“…The levels of malondialdehyde in patient 7 were 4.79, 7.38, 6.14, 6.36, 7.10, 5.37, 5.54, 4.70, 4.03, and 3.76 nmole/mL 4, 6, 9,11,12,14,15,16,18, and 26 days after ingestion, respectively. The levels of malon¬ dialdehyde in patient 8 were 10.64, 13.72, 6.40, 7.19, 5.86, 5.25, 6.15, 5.42, 5.46, 5.41, and 6.10 nmole/mL 4,6,11,13,15,18,20,22,25,27, and 34 days after ingestion, respectively. One of four patients in the subacute toxic reaction group (case 5) did not have an elevated malondialdehyde level.…”

Section: Classification Of Patientsmentioning

confidence: 92%

“…6 Only fresh serum was employed for measure¬ ment of malondialdehyde. As the value of serum malondialdehyde is dependent on patient age, control serum samples were obtained from fasting normal adults matched for age (in ten-year incre-ments) and sex.…”

Section: Methodsmentioning

confidence: 99%