Using Bosentan to Treat Paraquat Poisoning-Induced Acute Lung Injury in Rats

Zhang, Zhongchen; Jian, Xiangdong; Zhang, Wei; Wang, Jieru; Zhou, Qian

doi:10.1371/journal.pone.0075943

Cited by 17 publications

(26 citation statements)

References 20 publications

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“…Our data revealed a likely role for mitochondrial injury and apoptosis in the unfavorable cardiac responses to the environmental toxin paraquat. Although it is still premature to discern the precise mechanism of action underneath ET A knockout-offered protection against mitochondrial damage following paraquat exposure, our study supports the previously reported involvement of endothelin system in the pathogenesis of acute lung injury and multiple organ damage following paraquat exposure [21,44] and the likelihood therapeutic benefit of ET-1 receptor inhibition in the management of paraquat-induced acute lung injury [22]. Given that the current focus on the paraquat poisoning management, in particular in relevance to ET-1 receptor inhibition, resides in lung toxicity [8], considerable gap is present for the application of ET-1 receptor inhibition in the rigorous clinical modality of cardiac health management.…”

Section: Discussionsupporting

confidence: 89%

“…In addition, paraquatinduced cardiac contractile dysfunction was accompanied with unfavorable changes of mitochondrial proteins UCP2, HSP90 and PGC1a, the effect of which was mitigated or significantly attenuated by ET A knockout. Given the notion that endothelin may be involved in the pathogenesis of acute lung injury leading to multiple organ damage following paraquat exposure [21] and the effectiveness of ET-1 receptor inhibitors in the management of paraquat-induced acute lung injury [22], our experimental results favor an important role for endothelin system in particular ET A receptor in paraquat-induced myocardial dysfunction. The prooxidant herbicide paraquat has been widely used as a model to trigger ''oxidative cardiomyopathy'' including cardiac hypertrophy and myocardial contractile [36,37].…”

Section: Discussionmentioning

confidence: 80%

“…More evidence revealed that endothelin may be involved in the onset and progression of multiple organ damage triggered by paraquat exposure, indicating the clinical potential of endothelin levels as an index for evaluating multiple organ function damage and guidance of treatment [21]. Inhibition of ET-1 receptor using Bosentan has been shown to alleviate paraquat exposure-induced inflammation factor release and acute lung injury [22]. Nonetheless, the role of endothelin system has not been explored in acute paraquat exposure-induced cardiac damage.…”

Section: Introductionmentioning

confidence: 99%

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Cardiac-Specific Knockout of ETA Receptor Mitigates Paraquat-Induced Cardiac Contractile Dysfunction

Wang

Zheng

et al. 2015

Cardiovasc Toxicol

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Paraquat (1,1'-dim ethyl-4-4'-bipyridinium dichloride), a highly toxic quaternary ammonium herbicide widely used in agriculture, exerts potent toxic prooxidant effects resulting in multi-organ failure including the lung and heart although the underlying mechanism remains elusive. Recent evidence suggests possible involvement of endothelin system in paraquat-induced acute lung injury. This study was designed to examine the role of endothelin receptor A (ETA) in paraquat-induced cardiac contractile and mitochondrial injury. Wild-type (WT) and cardiac-specific ETA receptor knockout mice were challenged to paraquat (45 mg/kg, i.p.) for 48 h prior to the assessment of echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties, as well as apoptosis and mitochondrial damage. Levels of the mitochondrial proteinsfor biogenesis and oxidative phosphorylation including UCP2, HSP90 and PGC1α were evaluated. Our results revealed that paraquat elicited cardiac enlargement, mechanical anomalies including compromised echocardiographic parameters (elevated left ventricular end-systolic and end-diastolic diameters as well as reduced factional shortening), suppressed cardiomyocyte contractile function, intracellular Ca(2+) handling, overt apoptosis and mitochondrial damage. ETA receptor knockout itself failed to affect myocardial function, apoptosis, mitochondrial integrity and mitochondrial protein expression. However, ETA receptor knockout ablated or significantly attenuated paraquat-induced cardiac contractile and intracellular Ca(2+) defect, apoptosis and mitochondrial damage. Taken together, these findings revealed that endothelin system in particular the ETA receptor may be involved in paraquat-induced toxic myocardial contractile anomalies possibly related to apoptosis and mitochondrial damage.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

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Cardiac-Specific Knockout of ETA Receptor Mitigates Paraquat-Induced Cardiac Contractile Dysfunction

Wang

Zheng

et al. 2015

Cardiovasc Toxicol

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“…Numerous cases of poisoning involve the ingestion of diazepam, paraquat and organophosphorus pesticides (7). The prevalence of self-poisoning cases is 315-364 per 100,000 individuals per year (8).…”

Section: A B C a B Discussionmentioning

confidence: 99%

Esophageal mucosa exfoliation induced by oxalic acid poisoning: A case report

Wang

Kan

Jian

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. This study reports the case of a 44-year-old woman with oral oxalic acid poisoning. As the illness progressed, the patient exhibited severe metabolic acidosis, large-area esophageal mucosa injury and acute kidney injury, which required dialysis. A guide wire slipped out of position during the process of hemodialysis and moved back and forth in the veins, but was removed successfully by interventional endovascular treatment. However, the patient's esophageal mucosa exfoliated, which lead to severe benign esophageal stenosis and dysphagia. Balloon distention was conducted twice in the upper digestive tract using X-ray location in combination with a dumb-bell bladder and interventional wire. The patient exhibited convulsions, shock, embolism and loss of consciousness while undergoing the second balloon distention procedure. Following symptomatic treatment, the patient eventually remained in a stable condition, the digestive tract expansion procedure was not resumed and a jejunostomy was performed in order to facilitate enteral nutrition, which was administered via the jejunum and had little stimulatory effect on the pancreas. Following various treatments, the patient's condition improved markedly, with renal function returning to normal. IntroductionOxalic acid (OA), otherwise known as ethane diacid, is the most simple binary acid. OA exerts marked corrosive and toxic effects, and is commonly used in industry for metal polishing, cleaning and bleaching. OA can cause burns and poisoning, and although industrial cases are extremely rare, OA poisoning is being recognized as an emerging epidemic in certain rural communities as it is a component of widely produced household laundry detergents (1). The toxic effects of OA are primarily described in associated with ethylene glycol poisoning (2), as OA is a metabolite of ethylene glycol. As a final metabolic product, OA is ubiquitously present in plants, fungi and animals. Previously reported cases of isolated OA poisoning involve the consumption of food, medications and plants that contain the compound, such as star fruit and ascorbic acid (3). As OA is the primary component of certain domestic cleaning products, oral OA poisoning cases are not uncommon. Direct intoxication with OA is a relatively frequent occurrence, due to OA being a primary component of some household laundry detergents, and reports of the toxicological effects of OA poisoning in humans are not uncommon, including gastrointestinal effects, hypocalcemia secondary to calcium oxalate crystal formation and renal toxicity (4-6). However, it is relatively uncommon for exfoliation of the esophageal mucosa to be caused by OA poisoning. The present study reports a case of oral OA poisoning in a woman that developed large-area esophageal mucosa injury and acute kidney injury following self-ingestion of OA. The study was approved by the ethics committee of Qilu Hospital of Shandong University (Jinan, China), and informed consent was obtained from the patient. Case reportA 44-year-old woman oral consumed...

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“…The content of lung HYP was assayed using the chloramine-T method (18). The data are shown in as micrograms of HYP per milligram of lung tissue (μg/mg).…”

Section: Hydroxyproline (Hyp) Analysismentioning

confidence: 99%

Doxycycline attenuates paraquat-induced pulmonary fibrosis by downregulating the TGF-β signaling pathway

Hua

et al. 2017

J. Thorac. Dis.

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Background: Paraquat (PQ) is a highly efficient herbicide that remains widely used in agriculture.However, the inappropriate application of this herbicide may cause multiple organ injuries including pulmonary injury. In this study, we report that doxycycline (Doxy) treats PQ-induced pulmonary fibrosis (PF).Methods: Mice with PQ-induced PF were treated with different doses of Doxy by intragastric administration. Human lung cancer cell line A549 pre-treated with TGF-β1 (5 ng/mL) were treated with Doxy hydrochloride (3.4 μM). Results: PF was observed from day 28 in PQ-treated group and Doxy treatments significantly reduced pulmonary coefficient, histopathological score and collagen content in a dose-dependent manner. Doxy can inhibit the expression levels of plasma inflammation cytokines at day 28 after modeling and reduced inflammatory response at early stage of PQ-induced lung injury. Immunohistochemical staining assay and proteomic analysis indicated that Doxy could restore ectopic epithelial-mesenchymal transition (EMT) induced by PQ-treatment by regulating numerous TGF-β signaling related proteins. Conclusions:The findings suggest that Doxy can restore the balance of epithelial-mesenchymal cells and attenuate PQ-induced PF by downregulating the TGF-β signaling pathway.

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Using Bosentan to Treat Paraquat Poisoning-Induced Acute Lung Injury in Rats

Cited by 17 publications

References 20 publications

Cardiac-Specific Knockout of ETA Receptor Mitigates Paraquat-Induced Cardiac Contractile Dysfunction

Cardiac-Specific Knockout of ETA Receptor Mitigates Paraquat-Induced Cardiac Contractile Dysfunction

Esophageal mucosa exfoliation induced by oxalic acid poisoning: A case report

Doxycycline attenuates paraquat-induced pulmonary fibrosis by downregulating the TGF-β signaling pathway

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