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Daneshvar A, Jouzdani AF, Firozian F, Asl SS, Mohammadi M, Ranjbar A. Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats. Open Life Sci 2022; 17:1174-1181. [PMID: 36185402 PMCID: PMC9482421 DOI: 10.1515/biol-2022-0468] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 06/08/2022] [Accepted: 06/20/2022] [Indexed: 11/23/2022] Open
Abstract
Paraquat (PQ) is a nonselective herbicide that induces oxidative reactions and multiple-organ failure on exposure. Crocin, a carotenoid obtained from saffron, has demonstrated many therapeutic effects against neural conditions because of its antioxidant properties. In this study, 30 male Wistar rats were divided into 6 groups to evaluate the protective effects of crocin and crocin-loaded niosomes (NC) against PQ in the brain. The levels of total antioxidant capacity (TAC), lipid peroxidation (LPO), total thiol groups (TTG), superoxide dismutase (SOD), and catalase (CAT) activity were measured as the markers of redox status. Histopathological changes in the CA1 region of the hippocampus were evaluated by cresyl violet staining. Results indicated that both crocin and NC were able to attenuate the adverse effects of PQ at the histopathological level, which was following the changes in LPO (P < 0.0001), TAC (P < 0.01), and TTG (P < 0.05) level. The activity of CAT (P < 0.01) and SOD (P < 0.01) could be restored either by crocin or NC. Also, results indicated that nanoformulation of crocin in niosomes appears to be more promising. In conclusion, both crocin and NC showed favourable effects of PQ in the brain of rats, and were determined to be excellent agents to prevent acute toxicities of PQ. Furthermore, these two compounds can be known to provide neuroprotection.
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Affiliation(s)
- Afsoon Daneshvar
- Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, 6517838678, Iran
| | - Ali Fathi Jouzdani
- Department of Neuroscience, Neuroscience and Artificial Intelligence Research Group (NAIRG), Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran
- USERN Office, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Farzin Firozian
- Department of Pharmaceutics, Faculty of Pharmacy, Hamadan University of Medical Science, Hamadan, Iran
| | - Sara Soleimani Asl
- Department of Anatomy, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Mojdeh Mohammadi
- Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, 6517838678, Iran
| | - Akram Ranjbar
- Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, 6517838678, Iran
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Firouzian F, Pourshoja P, Nili-Ahmadabadi A, Ranjbar A. Hepatoprotective effect of N-acetylcystein loaded niosomes on liver function in paraquat-induced acute poisoning. PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY 2019; 160:146-153. [PMID: 31519249 DOI: 10.1016/j.pestbp.2019.08.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 08/12/2019] [Accepted: 08/12/2019] [Indexed: 06/10/2023]
Abstract
Paraquat (PQ) is widely used as a herbicide around the world. PQ intoxication causes liver disease mainly in mammals. N-acetyl cysteine (NAC) is a medication that has positive effects in reducing the liver intoxication caused by PQ. Here, after formulating a NAC noisome nanoparticle (NACNP), we compared the niosomes and NAC on liver toxicity caused by PQ. Thirty male rats were divided into 5 groups and were treated intraperitoneally with PQ and NAC and NACNP for 24 h. PQ group received 35 mg/kg/day of PQ, while NAC and NACNP groups were administered with 25 mg/kg/day of NAC and NACNP, respectively. In addition, 6 rats receiving saline solution were considered as control group. Serum and liver tissue samples were collected from all rats. Alanine (AST) and aspartate (ALT) aminotransferase levels, and oxidative stress biomarkers including total antioxidant capacity (TAC), lipid peroxidation (LPO), and total thiol groups (TTG) levels were determined. Histological samples were also analyzed using hematoxylin and eosin staining slides. PQ administration resulted in hepatic injury as evidenced by increases in serum AST and ALT levels (p < .001). NACNP decreased LPO, TAC, and TTG levels compered to PQ group in liver tissue. Treatment of animals with NACNP was significantly more effective than free NAC in reducing PQ-induced hepatotoxicity (p < .05). Histological evaluation showed that PQ caused tissue inflammation, which was reduced by NAC treatment. This reduction was stronger for NACNP. Given these results, the use of NACNP, compared to NAC, was more protective against the development of the PQ-induced liver toxicity.
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Affiliation(s)
- Farzin Firouzian
- Department of Pharmaceutics, Faculty of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Parisa Pourshoja
- Department of Pharmaceutics, Faculty of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran; Department of Toxicology & Pharmacology, Faculty of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Amir Nili-Ahmadabadi
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Akram Ranjbar
- Department of Toxicology & Pharmacology, Faculty of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran; Nutrition Health Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
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Heidary Dartoti H, Firozian F, Soleimani Asl S, Ranjbar A. Protective Role of Ce Nanoparticles Against the Hepatotoxicity Induced by Exposure to Paraquat. AVICENNA JOURNAL OF MEDICAL BIOCHEMISTRY 2018. [DOI: 10.15171/ajmb.2018.09] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Objectives: The present study aimed to investigate the antioxidant activity of cerium oxide nanoparticles (CeNPs) against paraquat (PQ)-induced liver injury in rats. Methods: Thirty-two male rats were divided into four 8-member groups and treated intraperitoneally with PQ and/or CeNPs for 14 days. Group 1 received PQ (5 mg/kg/d), group 2 received CeNPs (15, 30, and 60 mg/kg/d), group 3 received a combination of PQ (5 mg/kg/d) and CeNPs (15, 30, and 60 mg/kg/d), and group 4 (control group) received saline solution. Serum samples along with liver tissue samples were collected from all the rats. Oxidative stress (OS) biomarkers including total antioxidant capacity, lipid peroxidation, total thiol groups, DNA damage, and nitric oxide levels were determined. Histological samples were also analyzed using hematoxylin and eosin staining slides. Results: Levels of oxidative stress and hepatic tissue damage were significantly higher in the PQ group compared to the control group. CeNPs at a dose of 15 mg/kg showed the antioxidant activity and compromised the PQ-induced damage. Conclusion: In the scenario tested in this study, CeNPs could reduce the levels of OS, as well as hepatic damage induced by PQ.
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Affiliation(s)
- Hamid Heidary Dartoti
- Department of Toxicology and Pharmacology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Farzin Firozian
- Department of Pharmaceutical, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Sara Soleimani Asl
- Anatomy Department, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Akram Ranjbar
- Nutrition Health Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
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Suntres ZE. Exploring the potential benefit of natural product extracts in paraquat toxicity. Fitoterapia 2018; 131:160-167. [PMID: 30359726 DOI: 10.1016/j.fitote.2018.10.026] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 10/19/2018] [Accepted: 10/21/2018] [Indexed: 12/11/2022]
Abstract
Paraquat dichloride, a herbicide used for weed and grass control, is extremely toxic to humans and animals. The mechanisms of toxicity involve the redox cycling of paraquat resulting in the generation of reactive oxygen species and the depletion of the cellular NADPH. The major cause of death in paraquat poisoning is respiratory failure due to its specific uptake by and oxidative insult to the alveolar epithelial cells and inflammation with subsequent obliterating fibrosis. Paraquat also causes selective degeneration of dopaminergic neurons in the substantia nigra pars compacta, reproducing an important pathological feature of Parkinson disease. Currently, there are no antidotes for the treatment of paraquat poisoning and therapeutic management is mostly supportive and directed towards changing the disposition of the poison. The lack of effective treatments against paraquat poisoning has led to the exploration of novel compounds with antioxidant and/or anti-inflammatory properties. Recently, there is an interest in plant compounds, particularly those used in traditional medicine. Phytochemicals have been highlighted as a possible therapeutic modality for a variety of diseases due to their putative efficacies and safety. In this review, the status of plant extracts and traditional medicines in ameliorating the toxicity of paraquat is discussed.
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Affiliation(s)
- Zacharias E Suntres
- Medical Sciences Division, Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada.
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Kuo FC, Wu MR, Hsiao CY, Chen CY, Wang KT, Yeh HI, Su MI. Palliative Care on Patients With Paraquat Poisoning: Analysis of 90 Cases From 2005–2016. INT J GERONTOL 2018. [DOI: 10.1016/j.ijge.2018.02.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
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Zyoud SH. Investigating global trends in paraquat intoxication research from 1962 to 2015 using bibliometric analysis. Am J Ind Med 2018; 61:462-470. [PMID: 29537078 DOI: 10.1002/ajim.22835] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/08/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND Paraquat is considered to be the main pesticide involved in accidental and intentional poisoning, and is responsible for a high rate of morbidity and mortality. The aim of this study is to present a comprehensive bibliometric analysis of paraquat intoxication-related research. METHODS Data was retrieved in March 2017 from the Scopus database. An overview of the research on paraquat intoxication was presented alongside the information related to several bibliometric indicators, such as research trends, countries with their h-index, collaboration, hot issues, top-cited publications, journals, and institutions. RESULTS There were 1971 publications related to paraquat intoxication in the Scopus database that were published between 1966 and 2015. There was increasing research output in the field of paraquat intoxication during the period 2006-2015. The USA published the highest number of publications (n = 338), followed by Japan with 228 publications, and China with 159 publications. The USA and the UK achieved the greatest h-index values (h-index values of 49 and 31, respectively). The USA also achieved the highest number of publications involving international collaboration, with 55 publications, followed by the UK, with 18 publications. The most prevalent topics in this field were "acute paraquat intoxication," "toxic effects of paraquat to the lung," and "mechanism of paraquat toxicity." CONCLUSIONS Although a substantial amount of research has been produced on paraquat intoxication for most developed countries, there are research gaps regarding the international research agenda in this research area. The findings could be applied for prioritizing and organizing future research efforts related to paraquat toxicity.
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Affiliation(s)
- Sa'ed H Zyoud
- College of Medicine and Health Sciences, An-Najah National University, Poison Control and Drug Information Center (PCDIC), Nablus, Palestine
- Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
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Wu MR, Hsiao CY, Cheng CH, Liao FC, Chao CL, Chen CY, Yeh HI, Su MI. Is endotracheal intubation a non-beneficial treatment in patients with respiratory failure due to paraquat poisoning? PLoS One 2018; 13:e0195071. [PMID: 29590187 PMCID: PMC5874070 DOI: 10.1371/journal.pone.0195071] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Accepted: 03/18/2018] [Indexed: 12/01/2022] Open
Abstract
Introduction Paraquat poisoning can result in dysfunction of multiple organs, and pulmonary fibrosis with respiratory failure is the major cause of mortality. For terminally ill patients, some life-prolonging treatments can be non-beneficial treatments (NBT). The objective of this study was to determine if intubation is a NBT for patients with respiratory failure due to paraquat poisoning. Methods The study included 68 patients with respiratory failure due to paraquat poisoning. Patients were hospitalized at MacKay Memorial Hospital, Taitung Branch, Taiwan, between 2005 to April 2016. Composite outcomes of intra-hospital mortality, the rate of do-not-resuscitate (DNR) orders, prescribed medications, length of stay, and medical costs were recorded and compared between the do-not-intubate (DNI) group and endotracheal intubation (EI) group. Results Intra-hospital mortality rate for the entire population was 100%. There were significantly more patients with DNR orders in the DNI group (P = 0.007). There were no differences in the length of hospital stay. However, patients in DNI group had significantly less vasopressor use and more morphine use, shorter time in the intensive care unit, and fewer medical costs. Conclusion The procedure of intubation in patients with respiratory failure due to paraquat poisoning can be considered inappropriate life-prolonging treatment.
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Affiliation(s)
- Meng-Ruey Wu
- Division of Nephrology, Department of Internal Medicine, MacKay Memorial Hospital, Taitung branch, Taiwan
| | - Chia-Ying Hsiao
- Division of Nephrology, Department of Internal Medicine, MacKay Memorial Hospital, Taitung branch, Taiwan
| | - Chun-Han Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, MacKay Memorial Hospital, Taitung branch, Taiwan
| | - Feng-Ching Liao
- Division of Cardiology, Department of Internal Medicine, MacKay Memorial Hospital, Taitung branch, Taiwan
| | - Chuan-Lei Chao
- Division of Cardiology, Department of Internal Medicine, MacKay Memorial Hospital, Taitung branch, Taiwan
| | - Chun-Yen Chen
- Division of Cardiology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- MacKay Medical College, New Taipei City, Taiwan
| | - Hung-I Yeh
- Division of Cardiology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- MacKay Medical College, New Taipei City, Taiwan
| | - Min-I Su
- Division of Cardiology, Department of Internal Medicine, MacKay Memorial Hospital, Taitung branch, Taiwan
- MacKay Medical College, New Taipei City, Taiwan
- * E-mail:
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Ghorbani A, Masoumi K, Forouzan A, Rahmani A, Rahim F, Taeybi BT, Feli M. Effect of Pulse Therapy with Glucocorticoids and Cyclophosphamide in Patients with Paraquat Poisoning. HONG KONG J EMERG ME 2017. [DOI: 10.1177/102490791502200405] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Introduction Paraquat (PQ) is a widely used herbicide with a high mortality rate when ingested. The aim of the present study was to assess the effectiveness of repeated cyclosphosphamide (CP) and methylprednisolone (MP) combination in the treatment of PQ poisoning. Design Randomised, double-blinded, placebo-controlled trial. Methods Eligible participants were 47 patients with moderate to severe PQ poisoning within 24 hours of hospitalisation. Patients were allocated in a random fashion, 24 as the intervention and 23 as the control group. All patients received two cycles of eight hours of haemoperfusion with charcoal, and underwent emergency haemodialysis. After the dialysis, the intervention group received 15 mg/kg CP for two days and 1g MP for three days. The control group received routine supportive care. Outcome parameters, including mortality, incidence of hypoxia, hepatitis and renal failure were compared between the two groups. Results There were no significant differences between the two groups with regard to age, sex, baseline liver function test, creatinine, time from poisoning to dialysis, and time from poisoning to the hospitalisation. Although the incidence of hepatitis and acute renal failure did not differ significantly between the two groups, the incidence of hypoxia and mortality rate was lower in the intervention group. The number need-to-treat to reduce one mortality was 2.8. Conclusion The results suggest that CP and MP repeated treatment can reduce the mortality rate in moderate to severe PQ intoxication.
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Affiliation(s)
- A Ghorbani
- Razi Hospital, Department of Forensic Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz
| | - K Masoumi
- Imam Khomeini General Hospital, Department of Emergency Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - A Forouzan
- Imam Khomeini General Hospital, Department of Emergency Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ah Rahmani
- Razi Hospital, Department of Forensic Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz
| | - F Rahim
- Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - B Taherinezhad Taeybi
- Imam Khomeini General Hospital, Department of Emergency Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - M Feli
- Imam Khomeini General Hospital, Department of Emergency Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Kavousi-Gharbi S, Jalli R, Rasekhi-Kazerouni A, Habibagahi Z, Marashi SM. Discernment scheme for paraquat poisoning: A five-year experience in Shiraz, Iran. World J Exp Med 2017; 7:31-39. [PMID: 28261553 PMCID: PMC5316902 DOI: 10.5493/wjem.v7.i1.31] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2016] [Revised: 01/05/2017] [Accepted: 01/18/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate various schemes for paraquat poisoning and different variables that influence the outcome of acute paraquat poisoning.
METHODS In a cross-sectional study, the information about all cases of acute paraquat poisoning who were admitted to teaching hospitals affiliated to Shiraz University of Medical Sciences, in a five year period (September 2010 to September 2015) were evaluated. The variables included: Demographic data, medical assessment, therapeutic options, laboratory findings, and the outcomes. Data were analyzed using SPSS, version 22. Significant difference between groups was tested using t-test for continues outcomes and χ2 test for categorical. The significance level was considered to be P < 0.05.
RESULTS A total of 104 patients (66.3% male) were evaluated. The mean age of the female patients was 22.81 ± 9.87 years and the male patients’ was 27.21 ± 11.06 years. Ninety seven (93.3%) of all the cases were suicide attempts with mortality rate of 43.2%. Despite the necessity for emergency hemodialysis during the first 6 h of intoxication, none of the patients had dialysis during this time. Immunosuppressive and corticosteroid medications were not administrated in adequate dosage in 31.1% and 60% of the patients, respectively. Ingestion of more than 22.5 cc of paraquat and increase in creatinine level were the most important predictors of mortality.
CONCLUSION Treatment should start immediately for these patients. Moreover, creating a clinical guideline according to the findings can have an impact on the treatment procedure which seems to be necessary.
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Kim DS, Kang C, Kim DH, Kim SC, Lee SH, Jeong JH, Kang TS, Jung SM, Lee SB, Lee KW, Kim RB. External validation of the prognostic index in acute paraquat poisoning. Hum Exp Toxicol 2015; 35:366-70. [PMID: 25977258 DOI: 10.1177/0960327115586821] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE Some studies have evaluated the prognostic indicators associated with acute paraquat (PQ) poisoning. In this study, we externally validated the Yamaguchi index, which showed a good prognostic relevance in predicting the outcome of PQ poisoning. METHODS A retrospective analysis of 297 patients was performed. The Yamaguchi index was calculated using the following equation: Eq1 = (K(+) × HCO3(-))/(Creatinine × 0.088)(mEq/L) against time from PQ ingestion (T). The patients were divided into three groups: group A: Eq1 > 1500 - 399 × log T, group B: 930 - 399 × log T < Eq1 ≤ 1500 - 399 × log T, and group C: Eq1 ≤ 930 - 399 × log T). RESULTS The overall mortality rate was 65.3% (194 of 297). The mortality rates of the three groups stratified by the Yamaguchi index were 7.1% (2 of 28), 22.4% (15 of 67), and 87.6% (177 of 202). The area under the receiver-operating characteristic curve for predicting mortality from the external validation of the Yamaguchi index was 0.842 (95% confidence interval: 0.795-0.882). CONCLUSION The Yamaguchi index is a reliable prognostic factor and could be helpful in predicting mortality due to PQ poisoning.
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Affiliation(s)
- D S Kim
- Department of Emergency Medicine, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - C Kang
- Department of Emergency Medicine, Gyeongsang National University School of Medicine, Jinju, Republic of Korea Gyeongsang Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - D H Kim
- Department of Emergency Medicine, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - S C Kim
- Department of Emergency Medicine, Gyeongsang National University School of Medicine, Jinju, Republic of Korea Gyeongsang Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - S H Lee
- Department of Emergency Medicine, Gyeongsang National University School of Medicine, Jinju, Republic of Korea Gyeongsang Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - J H Jeong
- Department of Emergency Medicine, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - T S Kang
- Department of Emergency Medicine, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - S M Jung
- Department of Emergency Medicine, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - S B Lee
- Department of Emergency Medicine, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - K W Lee
- Department of Emergency Medicine, Catholic University of Daegu, Daegu, Republic of Korea
| | - R B Kim
- Department of Preventive Medicine, Dong-A University, Busan, Republic of Korea
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Cherukuri H, Pramoda K, Rohini D, Thunga G, Vijaynarayana K, Sreedharan N, Varma M, Pandit V. Demographics, clinical characteristics and management of herbicide poisoning in tertiary care hospital. Toxicol Int 2014; 21:209-13. [PMID: 25253933 PMCID: PMC4170565 DOI: 10.4103/0971-6580.139813] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Herbicide poisoning is most common method of suicide in India and it is associated with high morbidity and mortality. Among different herbicidal poisonings the most predominantly found poisonings are paraquat and glyphosate. These compounds are highly toxic and their poisonings require proper management techniques. High fatality is seen in these cases which are mainly due to its inherent toxicity and lack of effective treatment. Common symptoms of these poisonings includes gastrointestinal corrosive effects with mouth and throat, epigastric pain and dysphagia, acid-base imbalance, pulmonary edema, shock and arrhythmia. Long term health effects include pulmonary fibrosis, renal failure, hepatic failure, heart failure, multi-organ failure or death. No proven antidote exists for these poisonings. So the treatment is mainly supportive. Initially gastric lavage or whole-gut irrigation using adsorbents such as Fuller's earth, bentonite or activated charcoal is recommended. In case of renal failure hemodialysis or hemoperfusion may be considered. However novel approaches like treatment with N-acetylcysteine, vitamin C, vitamin E, cyclophosphamide may also be helpful.
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Affiliation(s)
- Harika Cherukuri
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka, India
| | - K Pramoda
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka, India
| | - D Rohini
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka, India
| | - Girish Thunga
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka, India
| | - K Vijaynarayana
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka, India
| | - N Sreedharan
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka, India
| | - Muralidhar Varma
- Department of Medicine, Kasturba Hospital, Manipal University, Manipal, Karnataka, India
| | - Vinay Pandit
- Department of Medicine, Kasturba Hospital, Manipal University, Manipal, Karnataka, India
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Wu WP, Lai MN, Lin CH, Li YF, Lin CY, Wu MJ. Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning: a nationwide study. PLoS One 2014; 9:e87568. [PMID: 24475310 PMCID: PMC3903773 DOI: 10.1371/journal.pone.0087568] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Accepted: 12/23/2013] [Indexed: 12/17/2022] Open
Abstract
Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST) in combination with hemoperfusion is also reported since 1971, the large-scale randomized control trials to confirm the effects of IST is difficult to be executed. Therefore, we designed this nationwide large-scale population-based retrospective cohort study to investigate the outcome of paraquat poisoning with hemoperfusion and the additional effects of IST combined with hemoperfusion. This nationwide retrospective cohort study utilized data retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 1811 hospitalized patients with a diagnosis of paraquat poisoning who received hemoperfusion between 1997 and 2009 were enrolled. The mean age of all 1811 study subjects was 47.3 years. 70% was male. The overall survival rate was only 26.4%. Respiratory failure and renal failure were diagnosed in 56.2% and 36% patients. The average frequency of hemoperfusion was twice. IST was added in 42.2% patients. IST significantly increases survival rate (from 24.3% to 29.3%, P<0.001). The combined IST with methylprednisolone, cyclophosphamide and dexamethasone associates with the highest survival rate (48%, P<0.001). Moreover, patients younger than 45 years of age in the IST group had the best survival (41.0% vs. 33.7%, p<0.001). Our results support the use of IST with hemoperfusion for paraquat-poisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age.
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Affiliation(s)
- Wen-Pyng Wu
- Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan
- Division of Nephrology, Chang-Bing Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Ming-Nan Lai
- Department of Statistics, Feng Chia University, Taichung, Taiwan
| | - Ching-Heng Lin
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Yu-Fen Li
- Institute of Biostatistics, China Medical University, Taichung, Taiwan
| | - Ching-Yuang Lin
- Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan
- Clinical Immunology Center, China Medical University Hospital, Taichung, Taiwan
| | - Ming-Ju Wu
- Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
- School of Medicine, Chung-Shan Medical University, Taichung, Taiwan
- Graduate Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan
- Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Xitun District, Taichung City, Taiwan
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Huh JW, Hong SB, Lim CM, Do KH, Lee JS, Koh Y. Sequential Radiologic and Functional Pulmonary Changes in Patients with Paraquat Intoxication. INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH 2013; 12:203-8. [PMID: 16967825 DOI: 10.1179/oeh.2006.12.3.203] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
The sequential changes of paraquat-induced pulmonary damage were studied using high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) in long-term follow-up. Among the cohort of 27 patients who had ingested paraquat, the HRCT findings showed a normal (n = 14) and an abnormal group (n = 13). Increased paraquat ingestion in the abnormal group was associated with more rapid and severe pulmonary changes. Ground-glass opacity on HRCT peaked on day 7 after ingestion. Between 2 weeks and 1 month, consolidation increased and pulmonary fibrosis progressed, and slow improvements were observed for up to six months. Compared with the PFT results obtained at 1 and 6.5 months, FVC, FEV1, and diffusing capacity all improved slightly. Lung changes after paraquat intoxication are functionally and radiologically reversible following treatment.
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Affiliation(s)
- Jin Won Huh
- Division of Pulmonary and Critical Care Medicine, Asan Medical Center, College of Medicine, University of Ulsan, 388-1, Pungnap-dong, Songpa-gu, Seoul, Korea
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15
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Choi JS, Jou SS, Oh MH, Kim YH, Park MJ, Gil HW, Song HY, Hong SY. The dose of cyclophosphamide for treating paraquat-induced rat lung injury. Korean J Intern Med 2013; 28:420-7. [PMID: 23864800 PMCID: PMC3712150 DOI: 10.3904/kjim.2013.28.4.420] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2012] [Revised: 06/13/2012] [Accepted: 08/21/2012] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND/AIMS Cyclophosphamide (CP) is a promising treatment for severe cases of paraquat (PQ) poisoning. We investigated the effective dose of CP for mitigating PQ-induced lung injury. METHODS Adult male Sprague-Dawley rats were allocated into five groups: control, PQ (35 mg/kg, intraperitoneal injection), and PQ + CP (1.5, 15, or 30 mg/kg). The dimensions of lung lesions were determined using X-ray microtomography (micro-CT), and histological changes and cytokine levels were recorded. RESULTS The micro-CT results showed that 15 mg/kg CP was more effective than 1.5 mg/kg CP for treating PQ-induced lung injury. At a dose of 1.5 mg/kg, CP alleviated the histological evidence of inflammation and altered superoxide dismutase activity. Using 15 mg/kg CP reduced the elevated catalase activity and serum transforming growth factor (TGF)-β1 level. CONCLUSIONS A CP dose of > 15 mg/kg is effective for reducing the severity of PQ-induced lung injury as determined by histological and micro-CT tissue examination, possibly by modulating antioxidant enzyme and TGF-β1 levels.
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Affiliation(s)
- Jae-Sung Choi
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Sung-Shick Jou
- Department of Radiology, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Mee-Hye Oh
- Department of Pathology, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Young-Hee Kim
- Department of Microbiology, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Min-Ju Park
- Department of Microbiology, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Hyo-Wook Gil
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Ho-Yeon Song
- Department of Microbiology, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Sae-Yong Hong
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
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Liu HL, Chen WL, Yang MC, Lin HM, Chou CC, Chang CF, Lin TJ, Liu KT, Lin YR. Prediction of early mortality in patients with paraquat intoxication. J Acute Med 2013. [DOI: 10.1016/j.jacme.2013.01.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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17
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Sanaei-Zadeh H. Can pirfenidone prevent paraquat-induced pulmonary fibrosis?—A hypothesis. Tzu Chi Med J 2012. [DOI: 10.1016/j.tcmj.2012.07.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Seifirad S, Keshavarz A, Taslimi S, Aran S, Abbasi H, Ghaffari A. Effect of pirfenidone on pulmonary fibrosis due to paraquat poisoning in rats. Clin Toxicol (Phila) 2012; 50:754-8. [DOI: 10.3109/15563650.2012.718783] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Sun Y, Zhang J, Yan Y, Chi M, Chen W, Sun P, Qin S. The protective effect of C-phycocyanin on paraquat-induced acute lung injury in rats. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2011; 32:168-174. [PMID: 21843796 DOI: 10.1016/j.etap.2011.04.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2010] [Revised: 04/16/2011] [Accepted: 04/27/2011] [Indexed: 05/31/2023]
Abstract
To investigate the potential protective effect of C-phycocyanin (PC) on paraquat (PQ)-induced acute lung injury, rats were divided into control, PQ-treated and PQ+PC-treated groups. Rats in PQ-treated group were orally administered with 50mg/kg PQ, and rats in PQ+PC-treated group were intraperitoneally injected with 50mg/kg PC after administration of PQ. At 8, 24, 48 and 72h after treatments, GSH-Px and SOD activities, MDA levels in plasma and BALF, HYP, NF-κB, IκB-α and TNF-α contents in lung tissues were measured. The pathological changes in lung were observed. After treatment with PC, the levels of MDA and the relative contents of NF-κB and TNF-α were significantly decreased, the activities of GSH-Px and SOD and the relative contents of IκB-α were significantly increased. The degree of rat lung damage was obviously reduced in PQ+PC-treated group. The results suggested that PC treatment significantly attenuated PQ-induced acute lung injury.
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Affiliation(s)
- Yingxin Sun
- Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
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20
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Jo YH, Kim K, Rhee JE, Suh GJ, Kwon WY, Na SH, Alam HB. Therapeutic hypothermia attenuates acute lung injury in paraquat intoxication in rats. Resuscitation 2011; 82:487-91. [PMID: 21236547 DOI: 10.1016/j.resuscitation.2010.11.028] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2010] [Revised: 10/25/2010] [Accepted: 11/26/2010] [Indexed: 12/18/2022]
Abstract
AIM OF THE STUDY Paraquat intoxication induces acute lung injury and numerous fatalities have been reported. The mechanism of toxic effect of paraquat is oxidative injury and inflammation. Therapeutic hypothermia has been known to have antioxidant and anti-inflammatory effects. This study was designed to evaluate the effect of therapeutic hypothermia on paraquat intoxication. METHODS Male Sprague-Dawley rats were given 50 mg/kg of paraquat intraperitoneally and divided into the normothermia (36-38°C) group and the hypothermia (30-32°C) group after 1h of paraquat administration. The hypothermia group underwent 2 h of hypothermia followed by 2 h of rewarming. In the survival study, mortality was observed for 24 h after paraquat administration. An in the second experiment, lung tissues and plasma were harvested at 6 h after paraquat administration. RESULTS The 12 h survival rate was significantly higher in the hypothermia group than in the normothermia group (100% vs. 50%, p<0.05), but survival rates for 24 h were not different. Acute lung injury score was lower in the hypothermia group than in the normothermia group (p<0.05). Thmalondialdehyde contents of lung tissues, plasma interleukin-6 and nitrite/nitrate concentrations were significantly decreased in the HT group compared to the NT group (p<0.05). CONCLUSION Therapeutic hypothermia delayed early mortality and attenuated acute lung injury in paraquat intoxication.
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Affiliation(s)
- You Hwan Jo
- Department of Emergency Medicine, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea
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21
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Efficacy of vitamin C against liver and kidney damage induced by paraquat toxicity. ACTA ACUST UNITED AC 2010; 64:431-4. [PMID: 21130632 DOI: 10.1016/j.etp.2010.10.009] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2010] [Revised: 10/03/2010] [Accepted: 10/25/2010] [Indexed: 12/13/2022]
Abstract
Paraquat has been demonstrated to be a highly toxic compound for humans and animals and many cases of acute poisoning and death have been reported over the past few decades. The current experiment aimed to examine if vitamin C (ascorbic acid) alleviates the morphological changes induced by paraquat (PQ) administration in the liver and kidney of male albino rats. Male adult rats received paraquat (PQ) (1.5 mg/kg body weight) daily for three weeks. Vitamin C (VC) at a dose of 20 mg/kg body weight was given concomitantly with PQ to rats. Animals were divided into three groups in this experiment (control, PQ and PQ+VC). The morphopathological manifestations were investigated in tissues from liver and kidney. As expected, PQ administration induced marked changes in the morphological structure of the liver and kidney in PQ demonstrated animals. Importantly, vitamin C administration restored PQ-induced changes in the studied organs. Vitamin C administration attenuated the morphological damages induced by PQ in the liver and kidney of experimental animals. Our results suggest an antitoxic effect of vitamin C against paraquat.
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Pyrrolidine dithiocarbamate attenuates paraquat-induced lung injury in rats. J Biomed Biotechnol 2009; 2009:619487. [PMID: 19639047 PMCID: PMC2715820 DOI: 10.1155/2009/619487] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2009] [Accepted: 05/26/2009] [Indexed: 11/17/2022] Open
Abstract
Paraquat (PQ) has been demonstrated that the main target organ for the toxicity is the lung. This study aimed to investigate the potential protective effect of PDTC on the PQ-induced pulmonary damage. Fifty-four rats were divided into control, PQ-treated and PQ+PDTC-treated groups. Rats in the PQ group were administrated 40 mg/kg PQ by gastric gavage, and PDTC group with 40 mg/kg PQ followed by injection of 120 mg/kg PDTC (IP). On the days 3, 7, 14 and 21 after treatments, the activities of GSH-Px, SOD, MDA level and the content of HYP were measured. TGF-β1 mRNA and protein were assayed by RT-PCR and ELISA. MDA level in plasma and BALF was increased and the activities of GSH-Px and SOD were decreased significantly in the PQ-treated groups (P < .05) compared with control group. While the activities of GSH-Px and SOD in the PQ+PDTC-treated groups was markedly higher than that of PQ-treated groups (P < .05), and in contrast, MDA level was lower. TGF-β1 mRNA and protein were significantly lower in the
PQ+PDTC-treated groups than that of PQ-treated groups (P < .05). The histopathological changes in the PQ+PDTC-treated groups were milder than those of PQ groups. Our results suggested that PDTC treatment significantly attenuated paraquat-induced pulmonary damage.
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23
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Abstracts of the European Association of Poisons Centres and Clinical Toxicologists XXV International Congress. Clin Toxicol (Phila) 2008. [DOI: 10.1080/07313820500207624] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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Lee J, Kwon W, Jo Y, Suh G, Youn Y. Protective effects of ethyl pyruvate treatment on paraquat-intoxicated rats. Hum Exp Toxicol 2008; 27:49-54. [PMID: 18480149 DOI: 10.1177/0960327108088976] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Although, numerous studies have attempted to reduce the oxygen radical injury induced by the antioxidants in paraquat intoxication, these antioxidant therapies have showed few survival benefits. Ethyl pyruvate (EP) may function as an effective scavenger of oxygen radicals, an anti-inflammatory agent and an energy source in many ischemia reperfusion models. The aim of this study was to evaluate the antioxidant and anti-inflammatory effects of EP on the lung and the liver tissues in paraquat-intoxicated rats. Rats were randomly given either a low (2 mg/kg i.p.) or high (40 mg/kg i.p.) EP dose, 30 min before or 1 h after paraquat (50 mg/kg i.p.) administration, and subsequently killed at 6 and 24 h. Glutathione (GSH) and malondialdehyde (MDA) levels of the lungs and the livers, and plasma nitric oxide (NO) concentrations were measured. Pretreatment of EP significantly decreased the MDA level in the lung and the liver tissues. EP also significantly decreased plasma NO concentrations at 6 h. EP pretreatment, however, failed to show significant change in GSH concentration. In post-treatment of EP, MDA levels in the lung tissue and plasma NO levels were significantly decreased. In conclusion, EP decreased the lipid peroxidation and seemed to exert an anti-inflammatory action in the paraquat intoxication rat model.
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Affiliation(s)
- Jh Lee
- Department of Emergency Medicine, Dongguk University College of Medicine, Gyeongsanbuk-do, Korea
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25
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Dinis-Oliveira RJ, Duarte JA, Sánchez-Navarro A, Remião F, Bastos ML, Carvalho F. Paraquat poisonings: mechanisms of lung toxicity, clinical features, and treatment. Crit Rev Toxicol 2008; 38:13-71. [PMID: 18161502 DOI: 10.1080/10408440701669959] [Citation(s) in RCA: 576] [Impact Index Per Article: 33.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Paraquat dichloride (methyl viologen; PQ) is an effective and widely used herbicide that has a proven safety record when appropriately applied to eliminate weeds. However, over the last decades, there have been numerous fatalities, mainly caused by accidental or voluntary ingestion. PQ poisoning is an extremely frustrating condition to manage clinically, due to the elevated morbidity and mortality observed so far and due to the lack of effective treatments to be used in humans. PQ mainly accumulates in the lung (pulmonary concentrations can be 6 to 10 times higher than those in the plasma), where it is retained even when blood levels start to decrease. The pulmonary effects can be explained by the participation of the polyamine transport system abundantly expressed in the membrane of alveolar cells type I, II, and Clara cells. Further downstream at the toxicodynamic level, the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. With this review we aimed to collect and describe the most pertinent and significant findings published in established scientific publications since the discovery of PQ, focusing on the most recent developments related to PQ lung toxicity and their relevance to the treatment of human poisonings. Considerable space is also dedicated to techniques for prognosis prediction, since these could allow development of rigorous clinical protocols that may produce comparable data for the evaluation of proposed therapies.
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Affiliation(s)
- R J Dinis-Oliveira
- REQUIMTE, Departamento de Toxicologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
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26
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Abstract
The author discusses whether the new paraquat formulation introduced in Sri Lanka is a step forward in reducing deaths from paraquat self-poisoning.
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27
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Dinis-Oliveira RJ, Remião F, Duarte JA, Ferreira R, Sánchez Navarro A, Bastos ML, Carvalho F. P-glycoprotein induction: an antidotal pathway for paraquat-induced lung toxicity. Free Radic Biol Med 2006; 41:1213-24. [PMID: 17015168 DOI: 10.1016/j.freeradbiomed.2006.06.012] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2006] [Revised: 06/26/2006] [Accepted: 06/27/2006] [Indexed: 01/12/2023]
Abstract
The widespread use of the nonselective contact herbicide paraquat (PQ) has been the cause of thousands of deaths from both accidental and voluntary ingestion. The main target organ for PQ toxicity is the lung. No antidote or effective treatment to decrease PQ accumulation in the lung or to disrupt its toxicity has yet been developed. The present study describes a procedure that leads to a remarkable decrease in PQ accumulation in the lung, together with an increase in its fecal excretion and a subsequent decrease in several biochemical and histopathological biomarkers of toxicity. The administration of dexamethasone (100 mg/kg ip) to Wistar rats, 2 h after PQ intoxication (25 mg/kg ip), decreased the lung PQ accumulation to about 40% of the group exposed to only PQ and led to an improvement in tissue healing in just 24 h as a result of the induction of de novo synthesis of P-glycoprotein (P-gp). The involvement of P-gp in these effects was confirmed by Western blot analysis and by the use of a competitive inhibitor of this transporter, verapamil (10 mg/kg ip), which, given 1 h before dexamethasone, blocked its protective effects, causing instead an increase in lung PQ concentration and an aggravation of toxicity. In conclusion, the induction of P-gp, leading to a decrease in lung levels of PQ and the consequent prevention of toxicity, seems to be a new and promising treatment for PQ poisonings that should be further clinically tested.
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Affiliation(s)
- R J Dinis-Oliveira
- REQUIMTE, Department of Toxicology, Faculty of Pharmacy, University of Porto, 4099-030 Porto, Portugal.
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Cho JH, Yang DK, Kim L, Ryu JS, Lee HL, Lim CM, Koh YS. Inhaled nitric oxide improves the survival of the paraquat-injured rats. Vascul Pharmacol 2005; 42:171-8. [PMID: 15820443 DOI: 10.1016/j.vph.2005.01.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2004] [Accepted: 01/04/2005] [Indexed: 11/17/2022]
Abstract
The purpose of this study was to evaluate the effects of inhaled nitric oxide (NO) on the paraquat-induced lung injury in rats. The rats were assigned to four groups: control; inhaled NO (5 ppm); paraquat (PQ, 30 mg/kg); and PQ+NO group. For first 18 h the inhalation of NO mixed with room air was performed. Total white blood cell (WBC), neutrophil, total protein, lactate dehydrogenase (LDH), transforming growth factor-beta1 (TGF-beta1) in serum and/or bronchoalveolar lavage (BAL) fluid, serum malonaldehyde (MDA), and myeloperoxidase (MPO) of lung were measured and lung histopathology were also reviewed. The 72-h survival rate of PQ group was 58%, but the survival rate of PQ+NO group, NO group and control group were 100%, respectively. The serum MDA and TGF-beta1 in BAL fluid and blood of PQ+NO group were significantly lower than those of PQ group. However, inhaled NO did not decrease the elevated total WBC and neutrophil counts, and total protein, LDH and MPO activity in the lung injured by PQ. The alveolar septal thickening and inflammatory cell infiltration were not different between PQ and PQ+NO groups. NO inhalation may be beneficial for the survival of paraquat-induced injured rats by attenuating lipid peroxidation and production of TGF-beta1.
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Affiliation(s)
- Jae Hwa Cho
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Inha University, Incheon, Republic of Korea
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29
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Hirata K, Yoshitomi S, Dwi S, Iwabe O, Mahakant A, Polchai J, Miyamoto K. Generation of reactive oxygen species undergoing redox cycle of nostocine A: a cytotoxic violet pigment produced by freshwater cyanobacterium Nostoc spongiaeforme. J Biotechnol 2004; 110:29-35. [PMID: 15099903 DOI: 10.1016/j.jbiotec.2003.12.014] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2003] [Revised: 11/13/2003] [Accepted: 12/08/2003] [Indexed: 11/27/2022]
Abstract
Nostocine A (1) is an extracellular cytotoxic violet pigment produced by the freshwater cyanobacterium, Nostoc spongiaeforme TISTR 8169. Treatment with 1 was found to accelerate the generation of reactive oxygen species (ROS) in the green alga, Chlamydomonas reinhardtii, in the light. In vitro analysis revealed that 1 specifically eliminated superoxide radical anion (O(2)(-)) among several ROS tested. During the course of the reaction, oxygen (O(2)) was simultaneously synthesized and the O(2) synthesizing rate increased with the amount of 1 added. In contrast, O(2)(-) generation occurred when NADPH or NADH was added to a solution of 1 under aerobic condition. The reduction potential of 1 is very similar to that of O(2) indicating that 1 and O(2) can easily exchange electrons depending on the mass balance between their oxidized and reduced forms. Based on these results, the following hypothesis is formulated for the mechanism of intracellular ROS generation by treatment with 1: 1 taken into the target cells is reduced specifically by intracellular reductants such as NAD(P)H. When the O(2) level is sufficiently higher than that of 1, the reduced product of 1 is immediately oxidized by O(2). This is accompanied by the synthesis of O(2)(-) from O(2). The generation of O(2)(-) successively occurs, undergoing repeated redox cycles of 1, when the levels of the reductant and O(2) are still dominant to promote these reactions. This similar intracellular ROS generation mechanism to that of paraquat may cause the cytotoxicity.
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Affiliation(s)
- Kazumasa Hirata
- Environmental Biotechnology Laboratory, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
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Higuchi A, Yonemitsu K, Koreeda A, Tsunenari S. Inhibitory activity of epigallocatechin gallate (EGCg) in paraquat-induced microsomal lipid peroxidation--a mechanism of protective effects of EGCg against paraquat toxicity. Toxicology 2003; 183:143-9. [PMID: 12504348 DOI: 10.1016/s0300-483x(02)00512-7] [Citation(s) in RCA: 41] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Recently we have reported that epigallocatechin gallate (EGCg), a major component of Japanese green tea, significantly increased the survival rate of paraquat (Pq) poisoned mice. This paper describes two biochemical activities of EGCg, which relate to its protective effects against Pq toxicity. EGCg inhibited Pq-induced microsomal malondialdehyde (MDA) productions in rat liver microsome system containing 40 microM FeSO(4). Forty micromolar EGCg inhibited MDA production significantly. EGCg may inhibit the Pq-induced MDA production by at least two mechanisms. One may be iron-chelating activity as the inhibition disappeared when excess amounts of FeSO(4) were added to the reaction mixture, which indicated that EGCg reduced iron driven lipid peroxidation by pulling out available irons in the reaction mixture. The other is radical scavenging activity. EGCg scavenged DMPO-OOH spin adducts generated by the microsome-Pq system. The dose response curve of EGCg was similar to that obtained by ascorbic acid which is a typical water-soluble radical scavenger. Although ascorbic acid had a potential activity of scavenging superoxide radicals, it can not be recommended to use for the treatment of Pq poisoning, because ascorbic acid acts as a pro-oxidant in the presence of free transition metal ions by accelerating the Fenton reaction (Fe(2+)+H(2)O(2)-->Fe(3+)+OH(-)+OH*), which is responsible for lipid peroxidation. On the contrary, EGCg inhibited iron-driven lipid peroxidation presumably not only by chelating to Fe ions but also by scavenging superoxide radicals, which are responsible for the reduction of ferric (Fe(3+)) to ferrous (Fe(2+)) that catalyzes the Fenton reaction. Chelating and radical scavenging activity of EGCg can be expected simultaneously in the occurrence of Pq toxicity, which may explain the protective effects of EGCg against Pq toxicity.
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Affiliation(s)
- Akihiro Higuchi
- Department of Forensic Medicine, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan.
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Gear AJ, Ahrenholz DH, Solem LD. Paraquat poisoning in a burn patient. THE JOURNAL OF BURN CARE & REHABILITATION 2001; 22:347-51; discussion 346. [PMID: 11570536 DOI: 10.1097/00004630-200109000-00011] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Paraquat is a bipyridyl compound widely used as a contact herbicide. Since its introduction in 1962, hundreds of deaths have occurred, usually after suicidal or accidental ingestion. Death after dermal absorption of paraquat is uncommon, but has occurred after either contact with undiluted paraquat, disruption of skin integrity, or prolonged exposure. It is the purpose of this case report to describe a patient who had fatal dermal paraquat absorption after a crop-dusting accident in which he sustained 37% TBSA burns. After 9.5 hours of cutaneous exposure, a paraquat level of 0.169 mg/ml was obtained at 20 hours, the standard lethal dose at 16 hours being 0.16 mg/ml. In light of the apparently irreversible pathophysiology of paraquat poisoning with plasma levels as low as 3 mg/L, prevention and early intervention are the best treatments. Our patient may have survived an otherwise routine thermal injury had his wounds been aggressively irrigated in the field.
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Affiliation(s)
- A J Gear
- Department of Plastic and Hand Surgery, Regions Hospital (a University of Minnesota-affiliated hospital), Saint Paul 55101, USA
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Abstract
An early feature of paraquat (PQ) toxicity is the influx of inflammatory cells, releasing proteolytic enzymes and oxygen free radicals, which can destroy the lung epithelium and result in pulmonary fibrosis. Therefore, the ability to suppress early lung injury seems to be an appropriate therapy of pulmonary damage before the development of irreversible fibrosis. Here I show curcumin confers remarkable protection against PQ lung injury. A single intraperitoneal injection of PQ (50 mg/kg) resulted in a significant rise in the levels of protein, angiotensin converting enzyme (ACE), alkaline phosphatase (AKP), N-acetyl-beta-D-glucosaminidase (NAG) and thiobarbituric acid reactive substances (TBARS), and neutrophils in the bronchoalveolar lavage fluid (BALF), while a decrease in glutathione levels. In paraquat rats bronchoalveolar lavage (BAL) cell TBARS concentration was increased with a simultaneous decrease in glutathione content. In addition, the data also demonstrated that PQ caused a decrease in ACE and glutathione levels and an increase in levels of TBARS and myeloperoxidase (MPO) activity in the lung. Interestingly, curcumin prevented the general toxicity and mortality induced by PQ and blocked the rise in BALF protein, ACE, AKP, NAG TBARS and neutrophils. Similarly, curcumin prevented the rise in TBARS content in both BAL cell and lung tissue and MPO activity of the lung. In addition, PQ induced reduction in lung ACE and BAL cell and lung glutathione levels was abolished by curcumin treatment. These findings indicate that curcumin has important therapeutic implications in facilitating the early suppression of PQ lung injury.
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Affiliation(s)
- N Venkatesan
- Department of Biochemistry, Central Leather Research Institute, Madras, India.
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Lin JL, Leu ML, Liu YC, Chen GH. A prospective clinical trial of pulse therapy with glucocorticoid and cyclophosphamide in moderate to severe paraquat-poisoned patients. Am J Respir Crit Care Med 1999; 159:357-60. [PMID: 9927343 DOI: 10.1164/ajrccm.159.2.9803089] [Citation(s) in RCA: 89] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Affiliation(s)
- J L Lin
- Department of Medicine and Poison Center, Chang Gung Memorial Hospital, Lin-Kou Medical Center, Chang Gung Medical College and University, Taipei, Taiwan, Republic of China
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Eisenman A, Armali Z, Raikhlin-Eisenkraft B, Bentur L, Bentur Y, Guralnik L, Enat R. Nitric oxide inhalation for paraquat-induced lung injury. JOURNAL OF TOXICOLOGY. CLINICAL TOXICOLOGY 1998; 36:575-84. [PMID: 9776960 DOI: 10.3109/15563659809028051] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND When ingested, concentrated paraquat can cause either rapid death from multisystem failure and cardiovascular shock or delayed death from progressive pulmonary fibrosis. Diquat ingestion does not usually cause pulmonary fibrosis, but produces early onset acute renal failure. CASE REPORT A 52-year-old male ingested approximately 50 mL of a solution containing 13% paraquat and 7% diquat (about 6650 mg of paraquat and 3500 mg of diquat), and subsequently developed adult respiratory distress syndrome and pulmonary fibrosis. Survival prediction employing the criteria of Hart et al. for paraquat plasma levels was 30%. From the probable amount of paraquat ingested, severe toxicity was expected. The clinical course was not consistent with significant diquat toxicity. Treatment included oral Fuller's earth, forced diuresis, hemofiltration, N-acetylcysteine, methylprednisolone, cyclophosphamide, vitamin E, colchicine, and delayed continuous nitric oxide inhalation. The patient recovered and pulmonary function was subsequently normal. CONCLUSION It is unclear which, if any, of the above treatments contributed to recovery, but the encouraging outcome suggests a possible benefit of nitric oxide inhalation in paraquat poisoning which deserves further study.
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Affiliation(s)
- A Eisenman
- Department of Internal Medicine B, Rambam Medical Center, Haifa, Israel.
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Lin JL, Wei MC, Liu YC. Pulse therapy with cyclophosphamide and methylprednisolone in patients with moderate to severe paraquat poisoning: a preliminary report. Thorax 1996; 51:661-3. [PMID: 8882069 PMCID: PMC472485 DOI: 10.1136/thx.51.7.661] [Citation(s) in RCA: 52] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND Severe paraquat poisoning causes considerable morbidity and mortality. High doses of cyclophosphamide and dexamethasone have been used to treat patients with paraquat poisoning, but with mixed results. The use of pulse methylprednisolone and cyclophosphamide was investigated in the treatment of moderately severe paraquat poisoning. METHODS During a six-year period 87 patients with paraquat poisoning were admitted to hospital, of whom 33 had moderate to severe intoxication. Seventeen patients received conventional treatment and served as historical controls, and 16 received intravenous infusions of cyclophosphamide 1 g daily for two days and methylprednisolone 1 g daily for three days. RESULTS There were no differences between the groups in age, sex, severity of paraquat poisoning (as assessed by urine dithionite tests), or in the time elapsed from ingestion to presentation at hospital or to the beginning of haemoperfusion. No differences were seen in biochemical measurements on the third day after paraquat poisoning. The mortality in the pulse therapy group was lower than that in the control group (4/16 (25%) versus 12/17 (70.6%), p = 0.01). All fatalities were from progressive respiratory failure. CONCLUSIONS Pulse therapy with cyclophosphamide and methylprednisolone may be effective in preventing respiratory failure and reducing mortality in patients with moderate to severe paraquat poisoning. Further controlled studies are needed to confirm this and to establish the mechanisms.
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Affiliation(s)
- J L Lin
- Division of Nephrology and Poison Center, Chang Gung Medical College, Taiwan, ROC
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Suntres ZE, Shek PN. Liposomal alpha-tocopherol alleviates the progression of paraquat-induced lung damage. J Drug Target 1995; 2:493-500. [PMID: 7773611 DOI: 10.3109/10611869509015919] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
The present study was carried out to investigate the efficacy of liposome-associated alpha-tocopherol in treating pulmonary damage caused by paraquat exposure. alpha-Tocopherol liposomes (8 mg alpha-tocopherol/kg body weight) or plain liposomes were intratracheally instilled into the lungs of rats 24 h after paraquat treatment (20 mg/kg, ip); treated animals were killed 8, 24 or 48 h after administration of the liposomal preparations. Lungs of animals exposed to paraquat were extensively damaged as evidenced by an increase in lung weight and decreases in pulmonary angiotensin converting enzyme and alkaline phosphatase activities. Also, paraquat treatment resulted in a significant reduction in glutathione (GSH) concentration in the lung and an elevation in microsomal lipid peroxidation levels, as measured by the formation of diene conjugates. Treatment of paraquat-injected rats with plain liposomes did not significantly alter paraquat-induced changes of all parameters examined. On the other hand, treatment of rats with alpha-tocopherol liposomes, 24 h after paraquat administration, resulted in a significant increase in pulmonary alpha-tocopherol concentrations as well as a reduction in paraquat-induced changes in lipid peroxidation, GSH concentration, and lung angiotensin converting enzyme and alkaline phosphatase activities. The results of the present study suggest that alpha-tocopherol, administered directly to the lung in a liposomal form, may serve as a potentially effective pharmacological agent in the treatment of paraquat-induced lung injury.
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Affiliation(s)
- Z E Suntres
- Operational Medicine Division, Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada
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Köppel C, von Wissmann C, Barckow D, Rossaint R, Falke K, Stoltenburg-Didinger G, Schnoy N. Inhaled nitric oxide in advanced paraquat intoxication. JOURNAL OF TOXICOLOGY. CLINICAL TOXICOLOGY 1994; 32:205-14. [PMID: 8145361 DOI: 10.3109/15563659409000452] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
No effective treatment is available for adult respiratory distress syndrome, pulmonary hypertension and progressive lung fibrosis in severe paraquat poisoning. A potentially beneficial effect of nitric oxide inhalation on the mean pulmonary artery pressure and gas exchange in a subject with advanced paraquat intoxication is reported. Eight days after the suicidal ingestion of an unknown dose of paraquat, a 52-year-old female had a PaO2 < or = 50 mm Hg despite ventilation with an FiO2 of 1 and a positive end-expiratory pressure of 14 to 18 cm H2O. After administration of 25 ppm nitric oxide, PaO2 increased and the mean pulmonary artery pressure and the right-to-left shunt decreased. Discontinuation of nitric oxide resulted in rapid reversal. Ventilatory function was stabilized for three days during nitric oxide inhalation but the patient developed massive pleural effusions and died on d 11 during an interruption of nitric oxide therapy. The response of serious paraquat intoxications to nitric oxide therapy may merit further study. A remarkable post-mortem finding was extensive myonecrosis supporting prolonged muscular retention of paraquat with toxic myopathy or neuromyopathy as a late manifestation of paraquat toxicity.
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Affiliation(s)
- C Köppel
- Universitätsklinikum Rudolf Virchow, Standort Charlottenburg, Freie Universität Berlin, Germany
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Suntres ZE, Hepworth SR, Shek PN. Protective effect of liposome-associated alpha-tocopherol against paraquat-induced acute lung toxicity. Biochem Pharmacol 1992; 44:1811-8. [PMID: 1333208 DOI: 10.1016/0006-2952(92)90076-u] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The present study was undertaken to investigate whether alpha-tocopherol, entrapped in liposomes and delivered directly to the lung, could protect against paraquat-induced lung damage in the rat. Plain liposomes (composed of dipalmitoylphosphatidylcholine, DPPC) or DPPC/alpha-tocopherol liposomes were administered intratracheally to animals 24 hr prior to an intraperitoneal injection of paraquat (20 mg/kg); rats were killed 24 or 48 hr after paraquat treatment. Results of this study showed that lungs of animals treated with paraquat were damaged extensively as evidenced by an increase in lung weight and a significant reduction in lung angiotensin-converting enzyme (ACE) activity and cytochrome P450 concentration. Furthermore, paraquat treatment resulted in a significant decrease in reduced glutathione (GSH) concentrations and a marked elevation in microsomal lipid peroxidation levels as measured by the formation of diene conjugates. Pretreatment of rats with DPPC liposomes alone did not alter significantly the paraquat-induced changes of all parameters examined. On the other hand, pretreatment of rats with DPPC/alpha-tocopherol liposomes 24 hr prior to paraquat challenge resulted in a significant increase in pulmonary alpha-tocopherol concentrations and antagonized paraquat-induced changes in lipid peroxidation, GSH/GSSG ratio, lung ACE activity and cytochrome P450 concentrations. Results of this study suggested that alpha-tocopherol, delivered directly to the lung in a liposomal formulation 24 hr prior to paraquat administration, confers protection against paraquat-induced lung damage.
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Affiliation(s)
- Z E Suntres
- Operational Medicine Section, Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada
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Salmona M, Donnini M, Perin L, Diomede L, Romano M, Marini MG, Tacconi MT, Luisetti M. A novel pharmacological approach for paraquat poisoning in rat and A549 cell line using ambroxol, a lung surfactant synthesis inducer. Food Chem Toxicol 1992; 30:789-94. [PMID: 1427517 DOI: 10.1016/0278-6915(92)90081-u] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Paraquat (PQ) is a widely used herbicide that causes acute adult respiratory distress syndrome (ARDS) and chronic lung damage (diffuse fibrosis). One of the earliest biochemical effects induced by PQ is damage to type II pneumocytes with consequent depletion of surfactant. With the aim of counteracting the toxic effects of PQ, a series of investigations were performed into the possible protective effect of the drug ambroxol, which induces the synthesis of surfactant in lung alveolar type II cells. The number of survivors and survival time of rats treated ip with 35 mg PQ/kg was significantly increased by 3 days of ambroxol pretreatment and by ambroxol treatment 30 min or 2 hr after PQ. Total phospholipid content in lung and bronchoalveolar lavage fluid (BALF) was significantly reduced 30 hr after treatment with PQ alone. The association of ambroxol with PQ significantly antagonized this reduction. In BALF the ratio between palmitic acid and stearic acid concentrations was significantly lower in animals treated with PQ alone but was returned to normal by the association with ambroxol. The cell line A549, exposed in vitro to PQ concentrations from 0.5 x 10(-4) to 2 x 10(-3) M, showed a significant dose-dependent loss of viability. Cells pretreated with ambroxol (10 mg/ml) were more resistant to PQ and their viability started to decrease significantly only from a PQ concentration of 0.8 x 10(-3) M. Membrane microviscosity was measured on the same cells. Cells treated with PQ alone showed a reduction of membrane microviscosity, which was significantly counteracted by ambroxol pretreatment. The curves of modification of membrane microviscosity of cells treated with PQ and with ambroxol plus PQ paralleled those of cell viability, indicating that the stimulation of surfactant synthesis in vitro may be a prerequisite for counteracting some of the early effects of PQ.
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Affiliation(s)
- M Salmona
- Laboratory for Enzyme Research, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
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Perriëns JH, Benimadho S, Kiauw IL, Wisse J, Chee H. High-dose cyclophosphamide and dexamethasone in paraquat poisoning: a prospective study. Hum Exp Toxicol 1992; 11:129-34. [PMID: 1349219 DOI: 10.1177/096032719201100212] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Between March 1986 and March 1988, 47 consecutive patients, whose paraquat intoxication was confirmed by urine testing, were enrolled in a prospective study on the treatment of paraquat poisoning. Fourteen received a standard treatment regimen consisting of fluid replacement and oral absorbents, and 33 received high-dose cyclophosphamide and dexamethasone, in addition to standard therapy. The case fatality rate in both treatment groups (63 and 61%) was similar. In addition, all 26 patients whose paraquat serum concentrations were measured and who had a probability of survival of less than 65% according the survival curve of Hart et al. died, regardless of therapy. These included four in the cyclophosphamide/dexamethasone group and two in the standard treatment group who had prior survival probabilities between 50 and 65%. This indicated that the cut-off curve relating mortality and paraquat serum concentrations was similar in both treatment groups. High-dose cyclophosphamide/dexamethasone treatment is unlikely to improve the prognosis of paraquat poisoning.
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Affiliation(s)
- J H Perriëns
- Department of Internal Medicine, Akademisch Ziekenhuis, Paramaribo, Suriname
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Affiliation(s)
- S M Pond
- University of Queensland Department of Medicine, Princess Alexandra Hospital, Brisbane
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Meredith TJ, Vale JA. Treatment of paraquat poisoning in man: methods to prevent absorption. HUMAN TOXICOLOGY 1987; 6:49-55. [PMID: 3546086 DOI: 10.1177/096032718700600108] [Citation(s) in RCA: 57] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Theoretically, absorption of an ingested dose of paraquat may be reduced by gastric lavage, induced emesis, whole-gut lavage or by the oral administration of absorbent substances. Animal experiments suggest that paraquat is absorbed poorly from the stomach and absorbed incompletely (less than 5%) from the small intestine over a 1-6 h period. Although gastric lavage would therefore seem a logical way to ameliorate the toxicity of an ingested dose of paraquat, peak plasma concentrations are attained rapidly and evidence for the efficacy of gastric lavage in man is poor. In 1977, a potent emetic (PP796) was added to liquid and solid formulations of paraquat because experiments in primates had demonstrated a fivefold reduction in toxicity. In man, ingestion of formulations containing an emetic is more likely to cause spontaneous vomiting within 30 min than non-emetic preparations. However, definite evidence of benefit, as judged by improved patient prognosis, has yet to be established. Gut lavage has been shown to remove only a small proportion of an ingested dose of paraquat. At the flow rates employed in man (75 ml/min), approximately 0.5-1.0 litres of lavage fluid/h may be absorbed across the intestinal wall. Since there is a theoretical risk of increasing paraquat absorption, the use of whole-gut lavage cannot be recommended. Bipyridilium herbicides are absorbed by soil and clay minerals, and montmorillonite in particular has been shown to be a strong binding agent in vitro. Accordingly, the use of Fuller's Earth (calcium montmorillonite) and Bentonite (sodium montmorillonite) for the treatment of poisoning has been investigated in animal models.(ABSTRACT TRUNCATED AT 250 WORDS)
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