Therapy with high‑dose long‑term antioxidant free radicals for severe paraquat poisoning: A pilot study

Hu,Shunlin; Qiao,Chuanhu; Yuan,Zhengli; Li,Min; Ye,Jiangfeng; Ma,Huimin; Wang,Jinghui; Xin,Siyi; Zhang,Jing

doi:10.3892/etm.2018.6823

Therapy with high‑dose long‑term antioxidant free radicals for severe paraquat poisoning: A pilot study

Authors:
- Shunlin Hu
- Chuanhu Qiao
- Zhengli Yuan
- Min Li
- Jiangfeng Ye
- Huimin Ma
- Jinghui Wang
- Siyi Xin
- Jing Zhang
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Affiliations: Department of Gastroenterology, Xiangyang First People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
Published online on: October 2, 2018 https://doi.org/10.3892/etm.2018.6823
Pages: 5149-5155
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

This study investigated the effects of high‑dose long‑term antioxidant free radicals on the mortality rate, creatinine (Cr) value, partial pressure of oxygen (PaO2), alanine aminotransferase (ALT), as well as the incidence rates of lung fibrosis and dysfunction in the treatment of patients with severe paraquat (PQ) poisoning [toxic dose, 20 ml stock solution (20% w/v)]. A total of 23 cases of severe PQ poisoning treated in Xiangyang First People's Hospital, Hubei University of Medicine were collected (group 1), and they received conventional treatments such as immunosuppressive agents and/or hemoperfusion. Six patients were given high‑dose long‑term antioxidant therapy on the basis of conventional treatments (group 2). After treatment, 6 out of the 23 patients in group 1 survived, and all the 6 patients in group 2 survived, with the survival rate of 26.1 vs. 100% (p<0.01). The lowest PaO2 value in group 1 was lower than that in group 2 (70.26±16.38 vs. 91.17±3.43 mmHg, p<0.01). The highest ALT value in group 1 was higher than that in group 2 (216.74±126.23 vs. 52.50±24.83 U/l, p<0.01). There was no significant difference in the incidence rate of lung fibrosis between the two groups of survived patients, but there were 6 patients that died of severe lung fibrosis in group 1. Besides, the incidence rate of lung dysfunction in patients in group 2 was significantly lower than that in survived patients in group 1 (p<0.01). High‑dose long‑term antioxidants are the most critical treatment option to improve the survival rate of high‑dose PQ poisoning, they increase the patient's PaO2, enhance liver function, reduce lung fibrosis and refine lung dysfunction.

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1	Cochemé HM and Murphy MP: Complex I is the major site of mitochondrial superoxide production by paraquat. J Biol Chem. 283:1786–1798. 2008. View Article : Google Scholar : PubMed/NCBI
2	Castello PR, Drechsel DA and Patel M: Mitochondria are a major source of paraquat-induced reactive oxygen species production in the brain. J Biol Chem. 282:14186–14193. 2007. View Article : Google Scholar : PubMed/NCBI
3	Dinis-Oliveira RJ, Duarte JA, Sánchez-Navarro A, Remião F, Bastos ML and Carvalho F: Paraquat poisonings: Mechanisms of lung toxicity, clinical features, and treatment. Crit Rev Toxicol. 38:13–71. 2008. View Article : Google Scholar : PubMed/NCBI
4	Weng CH, Chen HH, Hu CC, Huang WH, Hsu CW, Fu JF, Lin WR, Wang IK and Yen TH: Predictors of acute kidney injury after paraquat intoxication. Oncotarget. 8:51345–51354. 2017. View Article : Google Scholar : PubMed/NCBI
5	Gil HW, Hong JR, Jang SH and Hong SY: Diagnostic and therapeutic approach for acute paraquat intoxication. J Korean Med Sci. 29:1441–1449. 2014. View Article : Google Scholar : PubMed/NCBI
6	Gawarammana IB and Buckley NA: Medical management of paraquat ingestion. Br J Clin Pharmacol. 72:745–757. 2011. View Article : Google Scholar : PubMed/NCBI
7	Hsu CW, Lin JL, Lin-Tan DT, Chen KH, Yen TH, Wu MS and Lin SC: Early hemoperfusion may improve survival of severely paraquat-poisoned patients. PLoS One. 7:e483972012. View Article : Google Scholar : PubMed/NCBI
8	Bonilla E, Medina-Leendertz S, Villalobos V, Molero L and Bohórquez A: Paraquat-induced oxidative stress in drosophila melanogaster Effects of melatonin, glutathione, serotonin, minocycline, lipoic acid and ascorbic acid. Neurochem Res. 31:1425–1432. 2006. View Article : Google Scholar : PubMed/NCBI
9	Cappelletti G, Maggioni MG and Maci R: Apoptosis in human lung epithelial cells: Triggering by paraquat and modulation by antioxidants. Cell Biol Int. 22:671–678. 1998. View Article : Google Scholar : PubMed/NCBI
10	Moon JM and Chun BJ: The efficacy of high doses of vitamin C in patients with paraquat poisoning. Hum Exp Toxicol. 30:844–850. 2011. View Article : Google Scholar : PubMed/NCBI
11	Hong SY, Hwang KY, Lee EY, Eun SW, Cho SR, Han CS, Park YH and Chang SK: Effect of vitamin C on plasma total antioxidant status in patients with paraquat intoxication. Toxicol Lett. 126:51–59. 2002. View Article : Google Scholar : PubMed/NCBI
12	Hong SY, Yang JO, Lee EY and Lee ZW: Effects of N-acetyl-L-cysteine and glutathione on antioxidant status of human serum and 3T3 fibroblasts. J Korean Med Sci. 18:649–654. 2003. View Article : Google Scholar : PubMed/NCBI
13	Hong SY, Gil HW, Yang JO, Lee EY, Kim HK, Kim SH, Chung YH, Hwang SK and Lee ZW: Pharmacokinetics of glutathione and its metabolites in normal subjects. J Korean Med Sci. 20:721–726. 2005. View Article : Google Scholar : PubMed/NCBI
14	Jang YJ, Won JH, Back MJ, Fu Z, Jang JM, Ha HC, Hong S, Chang M and Kim DK: Paraquat induces apoptosis through a mitochondria-dependent pathway in RAW264.7 cells. Biomol Ther (Seoul). 23:407–413. 2015. View Article : Google Scholar : PubMed/NCBI
15	Musatov A and Robinson NC: Susceptibility of mitochondrial electron-transport complexes to oxidative damage. Focus on cytochrome c oxidase. Free Radic Res. 46:1313–1326. 2012. View Article : Google Scholar : PubMed/NCBI
16	Indo HP, Davidson M, Yen HC, Suenaga S, Tomita K, Nishii T, Higuchi M, Koga Y, Ozawa T and Majima HJ: Evidence of ROS generation by mitochondria in cells with impaired electron transport chain and mitochondrial DNA damage. Mitochondrion. 7:106–118. 2007. View Article : Google Scholar : PubMed/NCBI
17	Ortiz MS, Forti KM, Suárez Martinez EB, Muñoz LG, Husain K and Muñiz WH: Effects of antioxidant N-acetylcysteine against paraquat-induced oxidative stress in vital tissues of mice. Int J Sci Basic Appl Res. 26:26–46. 2016.PubMed/NCBI
18	Płoszaj T, Robaszkiewicz A and Witas H: Oxidative damage of mitochondrial DNA: The result or consequence of enhanced generation of reactive oxygen species. Postepy Biochem. 56:139–146. 2010.(In Polish). PubMed/NCBI
19	Bacsi A, Chodaczek G, Hazra TK, Konkel D and Boldogh I: Increased ROS generation in subsets of OGG1 knockout fibroblast cells. Mech Ageing Dev. 128:637–649. 2007. View Article : Google Scholar : PubMed/NCBI
20	Liu RM and Gaston Pravia KA: Oxidative stress and glutathione in TGF-beta-mediated fibrogenesis. Free Radic Biol Med. 48:1–15. 2010. View Article : Google Scholar : PubMed/NCBI
21	Cheresh P, Kim SJ, Tulasiram S and Kamp DW: Oxidative stress and pulmonary fibrosis. Biochim Biophys Acta. 1832:1028–1040. 2013. View Article : Google Scholar : PubMed/NCBI
22	Mittal M, Siddiqui MR, Tran K, Reddy SP and Malik AB: Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 20:1126–1167. 2014. View Article : Google Scholar : PubMed/NCBI
23	Mariappan N, Elks CM, Fink B and Francis J: TNF-induced mitochondrial damage: A link between mitochondrial complex I activity and left ventricular dysfunction. Free Radic Biol Med. 46:462–470. 2009. View Article : Google Scholar : PubMed/NCBI
24	Awadalla EA: Efficacy of vitamin C against liver and kidney damage induced by paraquat toxicity. Exp Toxicol Pathol. 64:431–434. 2012. View Article : Google Scholar : PubMed/NCBI
25	Boer LA, Panatto JP, Fagundes DA, Bassani C, Jeremias IC, Daufenbach JF, Rezin GT, Constantino L, Dal-Pizzol F and Streck EL: Inhibition of mitochondrial respiratory chain in the brain of rats after hepatic failure induced by carbon tetrachloride is reversed by antioxidants. Brain Res Bull. 80:75–78. 2009. View Article : Google Scholar : PubMed/NCBI
26	Kamata H, Honda S, Maeda S, Chang L, Hirata H and Karin M: Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell. 120:649–661. 2005. View Article : Google Scholar : PubMed/NCBI
27	He F, Xu P, Zhang J, Zhang Q, Gu S, Liu Y and Wang J: Efficacy and safety of pulse immunosuppressive therapy with glucocorticoid and cyclophosphamide in patients with paraquat poisoning: A meta-analysis. Int Immunopharmacol. 27:1–7. 2015. View Article : Google Scholar : PubMed/NCBI
28	Kim JH, Gil HW, Yang JO, Lee EY and Hong SY: Effect of glutathione administration on serum levels of reactive oxygen metabolites in patients with paraquat intoxication: A pilot study. Korean J Intern Med (Korean Assoc Intern Med). 25:282–287. 2010.
29	Kim SJ, Cheresh P, Jablonski RP, Williams DB and Kamp DW: The role of mitochondrial DNA in mediating alveolar epithelial cell apoptosis and pulmonary fibrosis. Int J Mol Sci. 16:21486–21519. 2015. View Article : Google Scholar : PubMed/NCBI
30	Yu WC, Tian LY and Cheng W: Efficacy study of edaravone and acetylcysteine towards bleomycin-induced rat pulmonary fibrosis. Int J Clin Exp Med. 8:8730–8739. 2015.PubMed/NCBI