Addition of Immunosuppressive Treatment to Hemoperfusion Is Associated with Improved Survival after Paraquat Poisoning: A Nationwide Study

Wu, Wen-Pyng; Lai, Ming‐Nan; Lin, Ching-Heng; Li, Yufen; Lin, Ching‐Yuang; Wu, Ming‐Ju

doi:10.1371/journal.pone.0087568

Cited by 63 publications

(71 citation statements)

References 34 publications

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“…On the other hand, MP, a kind of synthetic corticosteroid drug, can improve the survival rate of PQ patients mainly because of its potent antiinflammatory effects (Chen G.H. et al, 2002;Wu et al, 2014). In our study, MP treatment did not alleviate pulmonary fibrosis.…”

Section: Discussioncontrasting

confidence: 55%

Effects of rapamycin against paraquat-induced pulmonary fibrosis in mice

Shao

Luo

et al. 2015

J. Zhejiang Univ. Sci. B

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Background and aims: Ingestion of paraquat (PQ), a widely used herbicide, can cause severe toxicity in humans, leading to a poor survival rate and prognosis. One of the main causes of death by PQ is PQ-induced pulmonary fibrosis, for which there are no effective therapies. The aim of this study was to evaluate the effects of rapamycin (RAPA) on inhibiting PQ-induced pulmonary fibrosis in mice and to explore its possible mechanisms. Methods: Male C57BL/6J mice were exposed to either saline (control group) or PQ (10 mg/kg body weight, intraperitoneally; test group). The test group was divided into four subgroups: a PQ group (PQ-exposed, non-treated), a PQ+RAPA group (PQ-exposed, treated with RAPA at 1 mg/kg intragastrically), a PQ+MP group (PQ-exposed, treated with methylprednisolone (MP) at 30 mg/kg intraperitoneally), and a PQ+MP+RAPA group (PQ-exposed, treated with MP at 30 mg/kg intraperitoneally and with RAPA at 1 mg/kg intragastrically). The survival rate and body weight of all the mice were recorded every day. Three mice in each group were sacrificed at 14 d and the rest at 28 d after intoxication. Lung tissues were excised and stained with hematoxylin-eosin (H&E) and Masson's trichrome stain for histopathological analysis. The hydroxyproline (HYP) content in lung tissues was detected using an enzyme-linked immunosorbent assay (ELISA) kit. The expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) in lung tissues was detected by immunohistochemical staining and Western blotting. Results: A mice model of PQ-induced pulmonary fibrosis was established. Histological examination of lung tissues showed that RAPA treatment moderated the pathological changes of pulmonary fibrosis, including alveolar collapse and interstitial collagen deposition. HYP content in lung tissues increased soon after PQ intoxication but had decreased significantly by the 28th day after RAPA treatment. Immunohistochemical staining and Western blotting showed that RAPA treatment significantly down-regulated the enhanced levels of TGF-β1 and α-SMA in lung tissues caused by PQ exposure. However, RAPA treatment alone could not significantly ameliorate the lower survival rate and weight loss of treated mice. MP treatment enhanced the survival rate, but had no significant effects on attenuating PQ-induced pulmonary fibrosis or reducing the expression of TGF-β1 and α-SMA. Conclusions: This study demonstrates that RAPA treatment effectively suppresses PQ-induced alveolar collapse and collagen deposition in lung tissues through reducing the expression of TGF-β1 and α-SMA. Thus, RAPA has potential value in the treatment of PQ-induced pulmonary fibrosis.

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Section: Discussioncontrasting

confidence: 55%

Effects of rapamycin against paraquat-induced pulmonary fibrosis in mice

Shao

Luo

et al. 2015

J. Zhejiang Univ. Sci. B

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“…Paraquat intoxication has been found to cause kidney damage in humans (Kim et al, 2009; Reigart et al, 1999; Wu et al, 2014); however, little is known about the effects of chronic low-level exposure to this chemical. In our previous study, we observed a significant positive trend in the rate of ESRD associated with increasing lifetime use of paraquat among pesticide applicators (Lebov et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Pesticide exposure and end-stage renal disease risk among wives of pesticide applicators in the Agricultural Health Study

Lebov

Engel

Richardson

et al. 2015

Environmental Research

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Background Pesticide exposure has been found to cause renal damage and dysfunction in experimental studies, but epidemiological research on the renal effects of chronic low-level pesticide exposure is limited. We investigated the relationships between end-stage renal disease (ESRD) among wives of licensed pesticide applicators (N = 31,142) in the Agricultural Health Study (AHS) and (1) personal pesticide use, (2) exposure to the husband's pesticide use, and (3) other pesticide-associated farming and household activities. Methods AHS participants reported pesticide exposure via self-administered questionnaires at enrollment (1993–1997). ESRD cases were identified via linkage to the United States Renal Data System. Associations between ESRD and pesticide exposures were estimated with Cox proportional hazard regression models controlling for age at enrollment. Models of associations with farming and household factors were additionally adjusted for personal use of pesticides. Results We identified 98 ESRD cases diagnosed between enrollment and 31 December 2011. Although women who ever applied pesticides (56% of cohort) were less likely than those who did not apply to develop ESRD (Hazard Ratio (HR): 0.42; 95% CI: 0.28, 0.64), among women who did apply pesticides, the rate of ESRD was significantly elevated among those who reported the highest (vs. lowest) cumulative general pesticide use (HR: 4.22; 95% CI: 1.26, 14.20). Among wives who never applied pesticides, ESRD was associated with husbands' ever use of paraquat (HR = 1.99; 95% CI: 1.14, 3.47) and butylate (HR = 1.71; 95% CI: 1.00, 2.95), with a positive exposure–response pattern for husband’s cumulative use of these pesticides. Conclusions ESRD may be associated with direct and/or indirect exposure to pesticides among farm women. Future studies should evaluate indirect exposure risk among other rural populations.

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“…However, ingestion of the concentrated formulation is very toxic to humans, and it has been rigorously restricted or banned in many countries . Clinical management involves supportive care, as well as correction of acid base and electrolyte disturbances, and there is no specific antidotal treatment . Some studies mentioned that early haemoperfusion may improve patients' chances of survival in severe cases of acute paraquat poisoning …”

Section: Introductionmentioning

confidence: 99%

“…Clinical management involves supportive care, as well as correction of acid base and electrolyte disturbances, and there is no specific antidotal treatment . Some studies mentioned that early haemoperfusion may improve patients' chances of survival in severe cases of acute paraquat poisoning …”

Section: Introductionmentioning

confidence: 99%