Paraquat
Paraquat is a widely used herbicide, but is also a lethal poison. In some low- and middle-income countries (LMICs) paraquat is commonly available and inexpensive, making poisoning prevention difficult. Most of the people poisoned by paraquat have taken it as a means of self-poisoning. Standard treatment for paraquat poisoning prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited. The immune system plays an important role in exacerbating paraquat-induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination has been developed and studied as an intervention for paraquat poisoning 1).
2: Wang EW, Trojano ML, Lewis MM, Du G, Chen H, Brown GL, Jellen LC, Song I, Neely E, Kong L, Connor JR, Huang X. HFE H63D Limits Nigral Vulnerability to Paraquat in Agricultural Workers. Toxicol Sci. 2021 Apr 27;181(1):47-57. doi: 10.1093/toxsci/kfab020. PMID: 33739421; PMCID: PMC8081021.
3: Hwang I, Uchida H, Dai Z, Li F, Sanchez T, Locasale JW, Cantley LC, Zheng H, Paik J. Cellular stress signaling activates type-I IFN response through FOXO3-regulated lamin posttranslational modification. Nat Commun. 2021 Jan 28;12(1):640. doi: 10.1038/s41467-020-20839-0. PMID: 33510167; PMCID: PMC7843645.
4: Liu F, Yuan M, Li C, Guan X, Li B. The protective function of taurine on pesticide-induced permanent neurodevelopmental toxicity in juvenile rats. FASEB J. 2021 Jan;35(1):e21273. doi: 10.1096/fj.202001290R. PMID: 33368748.
5: Huang Y, Sun L, Zhu S, Xu L, Liu S, Yuan C, Guo Y, Wang X. Neuroprotection Against Parkinson's Disease Through the Activation of Akt/GSK3β Signaling Pathway by Tovophyllin A. Front Neurosci. 2020 Jul 9;14:723. doi: 10.3389/fnins.2020.00723. PMID: 32742256; PMCID: PMC7364155.
6: Song IY, Snyder AM, Kim Y, Neely EB, Wade QW, Connor JR. The Nrf2-mediated defense mechanism associated with HFE genotype limits vulnerability to oxidative stress-induced toxicity. Toxicology. 2020 Aug;441:152525. doi: 10.1016/j.tox.2020.152525. Epub 2020 Jun 12. PMID: 32540480.
7: Lei Y, Zhang ZF, Lei RX, Wang S, Zhuang Y, Liu AC, Wu Y, Chen J, Tang JC, Pan MX, Liu R, Liao WJ, Feng YG, Wan Q, Zheng M. DJ-1 Suppresses Cytoplasmic TDP-43 Aggregation in Oxidative Stress-Induced Cell Injury. J Alzheimers Dis. 2018;66(3):1001-1014. doi: 10.3233/JAD-180460. PMID: 30372676.
8: Nixon AM, Meadowcroft MD, Neely EB, Snyder AM, Purnell CJ, Wright J, Lamendella R, Nandar W, Huang X, Connor JR. HFE Genotype Restricts the Response to Paraquat in a Mouse Model of Neurotoxicity. J Neurochem. 2018 May;145(4):299-311. doi: 10.1111/jnc.14299. Epub 2018 Apr 1. PMID: 29315562.
9: Li LR, Sydenham E, Chaudhary B, Beecher D, You C. Glucocorticoid with cyclophosphamide for paraquat-induced lung fibrosis. Cochrane Database Syst Rev. 2014 Aug 7;(8):CD008084. doi: 10.1002/14651858.CD008084.pub4. PMID: 25099931.
10: Raghu K, Mahesh V, Sasidhar P, Reddy PR, Venkataramaniah V, Agrawal A. Paraquat poisoning: A case report and review of literature. J Family Community Med. 2013 Sep;20(3):198-200. doi: 10.4103/2230-8229.122023. PMID: 24672279; PMCID: PMC3957175.
11: Du G, Lewis MM, Sterling NW, Kong L, Chen H, Mailman RB, Huang X. Microstructural changes in the substantia nigra of asymptomatic agricultural workers. Neurotoxicol Teratol. 2014 Jan-Feb;41:60-4. doi: 10.1016/j.ntt.2013.12.001. Epub 2013 Dec 12. PMID: 24334261; PMCID: PMC3943901.
12: Li LR, Sydenham E, Chaudhary B, You C. Glucocorticoid with cyclophosphamide for paraquat-induced lung fibrosis. Cochrane Database Syst Rev. 2012 Jul 11;(7):CD008084. doi: 10.1002/14651858.CD008084.pub3. Update in: Cochrane Database Syst Rev. 2014;(8):CD008084. PMID: 22786512.
13: Li LR, Sydenham E, Chaudhary B, You C. Glucocorticoid with cyclophosphamide for paraquat-induced lung fibrosis. Cochrane Database Syst Rev. 2010 Jun 16;(6):CD008084. doi: 10.1002/14651858.CD008084.pub2. Update in: Cochrane Database Syst Rev. 2012;7:CD008084. PMID: 20556790.
14: Zhang ZJ, Zhou CY, Luo YJ, Xiong HW. Expression of heat shock protein 70 in lung tissues of acute paraquat poisoned rats and intervention of ulinastatin. World J Emerg Med. 2010;1(3):229-33. PMID: 25214974; PMCID: PMC4129680.
15: Liu J, Narasimhan P, Song YS, Nishi T, Yu F, Lee YS, Chan PH. Epo protects SOD2-deficient mouse astrocytes from damage by oxidative stress. Glia. 2006 Mar;53(4):360-5. doi: 10.1002/glia.20289. PMID: 16288465.
16: Taylor DM, Minotti S, Agar JN, Durham HD. Overexpression of metallothionein protects cultured motor neurons against oxidative stress, but not mutant Cu/Zn- superoxide dismutase toxicity. Neurotoxicology. 2004 Sep;25(5):779-92. doi: 10.1016/j.neuro.2004.02.002. PMID: 15288509.
17: Copin JC, Gasche Y, Li Y, Chan PH. Prolonged hypoxia during cell development protects mature manganese superoxide dismutase-deficient astrocytes from damage by oxidative stress. FASEB J. 2001 Feb;15(2):525-34. doi: 10.1096/fj.00-0330com. PMID: 11156968.
18: Webb DB, Ansari EJ, Wallis DI. An electrophysiological study of ganglion blockade by paraquat and diquat. Hum Toxicol. 1988 Nov;7(6):563-5. doi: 10.1177/096032718800700609. PMID: 3229767.
19: Vizek M, Frydrychova M, Houstek S, Palecek F. Effect of vagal cooling on lung functional residual capacity in rats with pneumonia. Bull Eur Physiopathol Respir. 1983 Jan-Feb;19(1):23-6. PMID: 6850143.
20: Kunc L, Kuncová M, Soldán F. The relationship between phospholipid amount and surface activity of lung washing. Folia Morphol (Praha). 1981;29(2):192-7. PMID: 6894434.
21: Chvalova M, Palecek F. Proceedings: The pattern of breathing in the rat. J Physiol. 1974 Oct;242(2):72P-73P. PMID: 4455845.