Inhaled Nitric Oxide in Advanced Paraquat Intoxication

Köppel, Claus; Wissmann, Ch. v.; Barckow, D.; Rossaint, Rolf; Falke, K. J.; Stoltenburg-Didinger, G.; Schnoy, N.

doi:10.3109/15563659409000452

Cited by 25 publications

(8 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Control of sarcoplasmic reticulum (SR) Ca 2+ release is voltage driven in skeletal muscle, however, L-type Ca 2+ current is the primary trigger for SR Ca 2+ release in cardiac muscle. While additional experimental work is needed to further clarify the exact mechanisms underlying the observed contractile decrement in cardiac and skeletal muscles, our findings corroborate previously published clinical studies which have described PAR-induced lesions in skeletal muscle [36], [37] and the heart [38]. Moreover, two cases of suicide from oral ingestion of PAR have been reported [39].…”

Section: Discussionsupporting

confidence: 89%

Vitamin E Ameliorates the Decremental Effect of Paraquat on Cardiomyocyte Contractility in Rats

et al. 2013

View full text Add to dashboard Cite

BackgroundExposure to pesticides and industrial toxins are implicated in cardiovascular disease. Paraquat (PAR) is a toxic chemical widely used as an herbicide in developing countries and described as a major suicide agent. The hypothesis tested here is that PAR induced myocardial dysfunction may be attributed to altered mechanisms of Ca2+ transport which are in turn possibly linked to oxidative stress. The mechanisms of PAR induced myocardial dysfunction and the impact of antioxidant protection was investigated in rat ventricular myocytes.MethodologyForty adult male Wistar rats were divided into 4 groups receiving the following daily intraperitoneal injections for 3 weeks: Group 1 PAR (10 mg/kg), Control Group 2 saline, Group 3 vitamin E (100 mg/kg) and Group 4 PAR (10 mg/kg) and vitamin E (100 mg/kg). Ventricular action potentials were measured in isolated perfused heart, shortening and intracellular Ca2+ in electrically stimulated ventricular myocytes by video edge detection and fluorescence photometry techniques, and superoxide dismutase (SOD) and catalase (CAT) levels in heart tissue.Principal FindingsSpontaneous heart rate, resting cell length, time to peak (TPK) and time to half (THALF) relaxation of myocyte shortening were unaltered. Amplitude of shortening was significantly reduced in PAR treated rats (4.99±0.26%) and was normalized by vitamin E (7.46±0.44%) compared to controls (7.87±0.52%). PAR significantly increased myocytes resting intracellular Ca2+ whilst TPK and THALF decay and amplitude of the Ca2+ transient were unaltered. The fura-2–cell length trajectory during the relaxation of the twitch contraction was significantly altered in myocytes from PAR treated rats compared to controls suggesting altered myofilament sensitivity to Ca2+ as it was normalized by vitamin E treatment. A significant increase in SOD and CAT activities was observed in both PAR and vitamin E plus PAR groups.ConclusionsPAR exposure compromised rats heart function and ameliorated by vitamin E treatment.

show abstract

Section: Discussionsupporting

confidence: 89%

Vitamin E Ameliorates the Decremental Effect of Paraquat on Cardiomyocyte Contractility in Rats

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Myopathy associated with PQ poisoning was reported, for the first time, by Saunders and coworkers in 1985 [39]. Koppel and colleagues [40] subsequently reported that extensive myonecrosis was observed in a specimen of postmortem intercostal muscle of a 52-year-old woman who had ingested an unknown dose of PQ and died on the 11 th day after ingestion. Vyver et al [41] described a case of a patient that died 5 days after ingestion of PQ, whose PQ levels were high in the skeletal muscle and an increase of creatinine kinase levels in blood appeared on the fourth day after hospital admission.…”

Section: Discussionmentioning

confidence: 99%

Postmortem Analyses Unveil the Poor Efficacy of Decontamination, Anti-Inflammatory and Immunosuppressive Therapies in Paraquat Human Intoxications

et al. 2009

View full text Add to dashboard Cite

BackgroundFatalities resulting from paraquat (PQ) self-poisonings represent a major burden of this herbicide. Specific therapeutic approaches have been followed to interrupt its toxic pathway, namely decontamination measures to prevent PQ absorption and to increase its excretion from organism, as well as the administration of anti-inflammatory and immunosuppressive drugs. Until now, none of the postmortem studies resulting from human PQ poisonings have assessed the relationship of these therapeutic measures with PQ toxicokinetics and related histopathological lesions, these being the aims of the present study.Methodology/Principal FindingsFor that purpose, during 2008, we collected human fluids and tissues from five forensic autopsies following fatal PQ poisonings. PQ levels were measured by gas chromatography-ion trap mass spectrometry. Structural inflammatory lesions were evaluated by histological and immunohistochemistry analysis. The samples of cardiac blood, urine, gastric and duodenal wall, liver, lung, kidney, heart and diaphragm, showed quantifiable levels of PQ even at 6 days post-intoxication. Structural analysis showed diffused necrotic areas, intense macrophage activation and leukocyte infiltration in all analyzed tissues. By immunohistochemistry it was possible to observe a strong nuclear factor kappa-B (NF-κB) activation and excessive collagen deposition.Conclusions/SignificanceConsidering the observed PQ levels in all analyzed tissues and the expressive inflammatory reaction that ultimately leads to fibrosis, we conclude that the therapeutic protocol usually performed needs to be reviewed, in order to increase the efficacy of PQ elimination from the body as well as to diminish the inflammatory process.

show abstract

“…Although the NADPH-diaphorase activity associated with NOSs has been reported to be a mechanism of PQ toxicity, despite the production of NO (Day et al 1999) and NO has also been directly implicated in PQmediated cytotoxicity (Berisha et al 1994a). However, conversely, other studies have described a protective role of NO following PQ exposure (Koppel et al 1994;Maruyama et al 1995;Cho et al 2005). Owing to the controversy in the published literature, the aim of this study is to elucidate the precise role of NO and NOSs in a model in which the three isoforms of NOSs are expressed, such that basal levels of NO are permanently present, which may lead to the formation of peroxynitrites due to the superoxide induced by PQ exposure.…”

Section: Introductionmentioning

confidence: 94%

Nitric Oxide-Mediated Toxicity in Paraquat-Exposed SH-SY5Y Cells: A Protective Role of 7-Nitroindazole

et al. 2009

View full text Add to dashboard Cite

The precise mechanism underlying the role of nitric oxide (NO) or nitric oxide synthases (NOSs) in paraquat-mediated toxicity is yet to be fully elucidated. The importance of the NADPH-diaphorase activity of NOSs in paraquat toxicity, in addition to the production of NO, has previously been reported as a mechanism of toxicity. However, other studies have highlighted the toxicity of NO alone and, conversely a protective role of NO in paraquat-mediated toxicity has also been described. The goal of this study was to clarify the involvement of NO and NOS in paraquat-mediated toxicity in an SH-SY5Y cell system, and to evaluate the putative role of 7-nitroindazole as a protective agent in human neural cells. Our results indicate that the three previously described isoforms of NOS are expressed in SH-SY5Y cells, with the data showing that these synthases act as paraquat diaphorases. While this process could occur at the expense of NO production, NO alone does play a toxic role, with its production leading to the formation of the toxicant peroxynitrite. Although the efficacies of the different inhibitors tested cannot be directly compared because the various NOS forms were probably inhibited to differing extents, the results support the idea that endogenous and inducible NO is a neurotoxic mediator of the effects of paraquat. The NADPH-diaphorase activity of NOS and NO production are therefore factors implicated in the toxicity mediated by the herbicide paraquat.

show abstract

Inhaled Nitric Oxide in Advanced Paraquat Intoxication

Cited by 25 publications

References 33 publications

Vitamin E Ameliorates the Decremental Effect of Paraquat on Cardiomyocyte Contractility in Rats

Vitamin E Ameliorates the Decremental Effect of Paraquat on Cardiomyocyte Contractility in Rats

Postmortem Analyses Unveil the Poor Efficacy of Decontamination, Anti-Inflammatory and Immunosuppressive Therapies in Paraquat Human Intoxications

Nitric Oxide-Mediated Toxicity in Paraquat-Exposed SH-SY5Y Cells: A Protective Role of 7-Nitroindazole

Contact Info

Product

Resources

About