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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acute intravenous and oral toxicity of single doses of paraquat dichloride was studied in the cynomolgus monkey. Renal handling and effects upon renal function were also investigated following an oral dose of [14C]paraquat. Clinical signs consisted of vomiting, anorexia and dyspnoea. By 48 h all animals showed signs of acute renal failure with oliguria, high plasma urea and SGPT levels and metabolic acidosis. Animals dosed orally showed similar, though less severe, signs to those dosed intravenously. The oral LD50 was approx. 70 mg paraquat cation/kg. Following an oral dose plasma levels peaked by 2 h, but were constant from 12 h to 24 h. Paraquat clearance was high initially and exceeded the creatinine and urea clearance, but fell off markedly after 14 h as renal failure developed. By 18 h urine production had ceased. It is concluded that acute renal failure and acute pulmonary damage are the main causes of death, with interstitial pulmonary fibrosis being a factor in animals surviving the acute phase.
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PMID:The toxicity and renal handling of paraquat in cynomolgus monkeys. 12 Jun 23

Paraquat, bipyridilium herbicide know to cause pulmonary fibrosis, was injected IP into rats. The rate of synthesis of collagen by lung minces from these and control rats was evaluated by measuring the rate of synthesis of hydroxyproline, a specific marker for collagen in lung. Synthesis was measured by incubating lung minces with radioactive proline for various amounts of time, after which proline specific activity and labeled hydroxyproline were determined. The size of the proline pool within the lung minces was significantly elevated in minces from rats that had been injected with paraquat, thus causing the specific activity of the [3H]proline precursor to be lower in these lungs than in those from control animals. Lung minces from rats administered paraquat made more collagen than did those from uninjected controls. The actual increase in rate of collagen synthesis correlated well with other independent estimates of paraquat-induced damage to the lungs.
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PMID:Paraquat-induced changes in the rate of collagen biosynthesis by rat lung explants. 73 65

Ingestion or injection of the herbicide paraquat (1,1'-dimethyl-4,4'-dipyridylium dichloride) has caused more than 120 deaths in humans. Most have been due to respiratory failure caused by pulmonary edema, hemorrhage, and atelectasis, or subsequent pulmonary fibrosis. Paraquat is concentrated in lung tissue and is believed to cause superoxide radical formation in the presence of oxygen and suitable electron donors. Exposure to increased concentrations of oxygen has been reported to accelerate the toxicity of paraquat. The therapeutic efficacy of a reduced oxygen environment was investigated by exposing paraquat-poisoned mice to 10% oxygen after stepwise drops from 14% oxygen. Sixty-one mice were given intraperitoneal injections of 27 mg. per kg. of paraquat. The 25 mice in hypoxia for 7 days had a 32% mortality rate versus a 78% mortality rate for the remainder of the mice in room air, p less than 0.01. After a dose of 20 mg. per kg. of paraquat administered intraperitoneally, 24 mice in hypoxia had a 25% mortality rate versus 51% for 35 animals in room air. Brief exposures of the hypoxic group to "normoxia" (room air) led to pulmonary edema and death. The continuous exposure of paraquat-poisoned animals to hypoxic environments was protective. This approach may be useful in other oxidant lung injuries.
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PMID:Hypoxic protection in paraquat poisoning. 99 61

Paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) has in the last decade gained popularity as an effective weedicide. It is marketed for commercial use as a liquid concentrate Gramoxone ICI (20% paraquat). Accidental or intentional ingestion of Gramoxone has caused 232 human deaths between 1964 and 1973 (Anon 1974). Most human patients suffer transient renal and hepatic insufficiency and pulmonary oedema followed after a latent period by progressive pulmonary fibrosis leading to death from respiratory failure (Harrison 1972). The clinical features of non-fatal paraquet poisoning in a cat and the clinical and pathological findings in fatal poisoning in a dog are reported.
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PMID:Paraquat poisoning in a dog and cat. 125 80

Paraquat is a potent herbicide, very toxic in the concentrated liquid form as supplied to farmers. Suicidal poisoning represents a serious emergency with a known high mortality rate. Suicidal poisoning following the parenteral route has been rarely reported. A 16-year-old girl was admitted to our emergency unit after subcutaneous injection of gramoxone 20% (about 400 mg of paraquat). Despite immediate surgical excision and revision, and subsequent antioxidant treatment with N-acetylcysteine (400 mg/kg/day during 48 hours), she died 17 days later from refractory hypoxemia following pulmonary fibrosis. From this observation and from the literature, it appears that an effective treatment does not depend on changes in the toxicokinetics of the herbicide (hemoperfusion, antidotes, drugs).
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PMID:[Fatal voluntary poisoning by parenteral paraquat]. 192 59

Paraquat is a bipyridyl compound with no known chronic toxicity or teratogenicity. It is poorly absorbed when inhaled, but causes severe illness when ingested orally, death usually occurring within 2 days of ingestion of 50 mg/kg. At lower doses death may be delayed for several weeks. The toxic compound accumulates in lung tissue where free radicals are formed, lipid peroxidation is induced and nicotinamide adenine dinucleotide phosphate (NADPH) is depleted. This produces diffuse alveolitis followed by extensive pulmonary fibrosis. The most important prognostic indicator is the quantity of paraquat absorbed, as shown by the plasma paraquat concentration. While renal failure will develop in the majority of those patients who eventually die, it may not, if present alone, indicate a fatal outcome. The absence of caustic burns in the upper digestive tract indicates a good prognosis. Treatment of paraquat poisoning remains ineffective, but Fuller's earth, activated charcoal and resins may prevent some absorption of the toxin. When tubular necrosis occurs, renal excretion of the compound decreases rapidly. A 3-compartment pharmacokinetic model has been described following ingestion of tracer doses including a 'deep' compartment for active pulmonary accumulation. Haemodialysis, haemoperfusion and forced dialysis have been attempted, with no clear improvement in survival rates. Superoxide dismutase, glutathione peroxidase, N-acetylcysteine and other 'free radical scavengers' have failed to alter the outcome in poisoned patients. Other theoretical treatments, such as deferoxamine, immunotherapy, NADPH repletion and lung transplantation still require clinical validation.
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PMID:Paraquat poisoning. An overview of the current status. 219 50

It is well known that Paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride), used widely as a herbicide, causes a primary toxic effect in the lungs of humans and laboratory animals. This paper describes the pulmonary changes of chronic paraquat poisoning in rats, comparing scanning electron microscopic findings. Twenty-four rats were given repeated injections of 10/kg body weight paraquat intraperitoneally for 6 consecutive months, and six control rats were given 0.9% NaCl solution. The animals exposed to paraquat showed thickening of alveolar septum, inflammatory cell infiltration, interstitial fibrosis, and marked proliferation of alveolar macrophages. Among them four rats (21%) showed the typical findings of diffuse pulmonary fibrosis. Lesions were more severe at the subpleural region of the lung. The desquamation of alveolar epithelial cells and subsequent exposure of the basement membranes were observed in places. Although alveolar epithelial cells both in the type I and the type II were prolific, the type II cells showed partial loss of microvilli and projections. These findings may indicate the lowering of the type II cell function and subsequent decrease of surfactant excretion which causes respiratory insufficiency. Furthermore, alveolar macrophages showed a tendency to increase in number with progressive development of fibrosis. This tendency may support the hypothesis by Schoenberger et al., in which alveolar macrophages release both fibronectin and a growth factor for fibroblast after paraquat exposure.
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PMID:[Scanning electron microscopic study of rat lungs in experimental chronic paraquat poisoning]. 226 8

A 20-year-old man committed suicide by drinking 50-100 ml of a 20% solution of Paraquat (Gramoxone). He died 24 days later from progressive pulmonary fibrosis (Paraquat lung) despite intensive therapy to combat the toxicity of the poison to lung, kidney, and liver. At necropsy, brain damage was found in the form of moderate neuronal depletion, probably secondary to anoxia, and damage to the central white matter and particularly the brain around the lateral and third ventricles. Examination of the brain by electron microscopy showed oedema and destruction of myelin with abundant myelin breakdown products, and astrocytic fibrous gliosis.
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PMID:Brain damage due to paraquat poisoning: a fatal case with neuropathological examination of the brain. 320 34

Paraquat (PQ) is a herbicide known to generate O2 radicals and to injure lung epithelial cells, leading eventually to pulmonary fibrosis. To test for the possible existence of a direct cytotoxic action of PQ on endothelial cells, we have studied, for up to 5 days, the action of 10(-6) to 10(-4) M PQ on primary cultures of pig aortic endothelial cells and compared these effects to those obtained with exposure to 95% O2-5% CO2. The decrease in DNA and protein content of Petri dishes and the increase in lactate dehydrogenase release were found to depend on PQ concentration and the duration of exposure to PQ. The toxic effects of hyperoxia were intermediate, ranging between those obtained with 10(-5) and 10(-4) M PQ. Hyperoxia and 10(-4) M PQ produced a similar marked inhibition of DNA synthesis after a 1-day period of exposure. Combined exposure to both PQ and hyperoxia resulted in changes comparable to those obtained with hyperoxia alone (decrease in protein and DNA content) or PQ alone (lactate dehydrogenase release). Additive effects were seen only for the inhibition of DNA synthesis. The selenomethionine-related increase in glutathione peroxidase activity had a protective effect against hyperoxia-induced lactate dehydrogenase release but not against PQ induced cytolysis. Finally, shorter exposures to O2 and PQ revealed the existence of a trend toward recovery only for cells exposed to hyperoxia. The prolonged toxic action of PQ could not be related to PQ accumulation and storage by endothelial cells. These studies indicate that PQ can exert a direct, dose-dependent, and prolonged cytotoxic effect on cultured endothelial cells.
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PMID:Direct toxic effects of paraquat and oxygen on cultured endothelial cells. 396 1

Paraquat, a widely used herbicide, can cause severe and often fatal pulmonary fibrosis in humans and in laboratory animals. Although paraquat is known to be directly cytotoxic to lung parenchymal cells, the mechanism by which this leads to pulmonary fibrosis is not completely understood. In a model of paraquat-induced pulmonary fibrosis using the cynomolgus monkey, the administration of paraquat (10 mg/kg/wk subcutaneously for 2 consecutive wk) was followed by an alveolitis comprised of neutrophils and macrophages in the exposed animals as evaluated by lung morphologic examination and bronchoalveolar lavage. The lungs of the exposed animals showed typical interstitial fibrosis within 4 to 8 wk. At 1 to 2 wk after paraquat exposure, bronchoalveolar lavage cells harvested from the paraquat-exposed animals were spontaneously releasing a chemotactic factor for neutrophils, thus providing a possible mechanism for the recruitment of neutrophils to the alveolar structures. Lavage fluid from paraquat-exposed animals contained increased amounts of the fibroblast chemoattractant fibronectin (paraquat, 3.1 +/- 0.3 ng/micrograms albumin; control, 1.6 +/- 0.7 ng/micrograms albumin; p less than 0.05), and alveolar macrophages from these animals showed increased fibronectin production suggesting that local production accounted for part of the increased amounts of this glycoprotein (paraquat, 6.1 +/- 2.5 ng/10(6) cell/h; control, 1.4 +/- 0.5 ng/10(6) cell/h; p less than 0.05). In addition, alveolar macrophages from the exposed animals were spontaneously releasing a growth factor for fibroblasts, and normal alveolar macrophages exposed to paraquat in vitro were induced to release this growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Paraquat-induced pulmonary fibrosis. Role of the alveolitis in modulating the development of fibrosis. 670 75


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