Ginsenoside Rg3 Alleviates Rotenone-induced Lung Injury in Mice by Its Anti-oxidative Properties
DOI:
https://doi.org/10.22270/ajprd.v9i6.1039Keywords:
Ginsenoside Rg3, rotenone, acute lung injury, oxidative stressAbstract
Objectives: Acute lung injury is commonly found in patients with insecticide poisoning and the pathogenesis is related to oxidative stress. Ginsenoside Rg3, one of the main constituents of Panax ginseng C.A. Meyer, shows an anti-oxidative activity. The aim of this study was to evaluate whether ginsenoside Rg3 can alleviate lung injury induced by rotenone in mice.
Methods: C57BL/6J male mice were divided into five groups (n=11). The mice in ginsenoside Rg3 groups were treated with ginsenoside Rg3 at dose of 5, 10 or 20 mg/kg. Except for the control group, mice were challenged intragastrically with rotenone at dose of 30 mg/kg, once a day for 6 weeks. Subsequently, the lung tissues of mice were collected. The effect of ginsenoside Rg3 on rotenone-induced lung injury was observed by hematoxylin and eosin staining. The oxidative stress in lung tissues were also examined.
Results: Rotenone induced substantial hemorrhage, alveolar wall thickness and neutrophils infiltration. These structural damages were attenuated significantly by ginsenoside Rg3 treatment. The lung injury induced by rotenone was associated with oxidative stress in lung tissues of mice. Compared with the control group, rotenone exposure resulted in the increase of malondialdehyde (MDA), the decreases of the activities of superoxide dismutase (SOD), glutathione peroxidase (GHS-Px), and the glutathione (GSH) content. Nevertheless, ginsenoside Rg3 treatment not only reduced MDA production but also increased the activities of SOD, GSH-Px, and the content of GSH in lung tissue of mice.
Conclusion: Taken together, this study demonstrated that ginsenoside Rg3 has potential to ameliorate rotenone-induced lung injury and the mechanism of action of ginsenoside Rg3 is mediated by its anti-oxidative properties.
Downloads
References
2. Gunnell D, Eddleston M, Phillips MR, Konradsen F. The global distribution of fatal pesticide self-poisoning: systematic review. BioMed Central public health. 2007; 7:357. doi: 10.1186/1471-2458-7-357.
3. Hulse EJ, Clutton RE, Drummond G, Eddleston M. Translational toxicological research: investigating and preventing acute lung injury in organophosphorus insecticide poisoning. Journal of the Royal Army Medical Corps. 2014; 160(2):191-2. doi: 10.1136/jramc-2013-000207.
4. Bellani G, Laffey JG, Pham T, Fan E, Brochard L et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. Journal of the American Medical Association. 2016; 315(8):788-800. doi: 10.1001/jama.2016.0291.
5. Li N, Ragheb K, Lawler G, Sturgis J, Rajwa B et al. Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. The Journal of biological chemistry. 2003; 278(10):8516-25. doi: 10.1074/jbc.M210432200.
6. Hasan W, Kori RK, Jain J, Yadav RS, Jat D. Neuroprotective effects of mitochondria-targeted curcumin against rotenone-induced oxidative damage in cerebellum of mice. Journal of biochemical and molecular toxicology. 2020; 34(1):e22416. doi: 10.1002/jbt.22416.
7. Yu JH, Huang CF, Wang TH, Hung DZ, Mu HW et al. Oxidative storm in a patient with acute rotenone-containing plant poisoning. The American journal of emergency medicine. 2020; 38(6):1296. doi: 10.1016/j.ajem.2020.01.019.
8. Bongard RD, Yan K, Hoffmann RG, Audi SH, Zhang X et al. Depleted energy charge and increased pulmonary endothelial permeability induced by mitochondrial complex I inhibition are mitigated by coenzyme Q1 in the isolated perfused rat lung. Free radical biology & medicine. 2013; 65:1455-1463. doi: 10.1016/j.freeradbiomed.2013.07.040.
9. 9.Audi SH, Merker MP, Krenz GS, Ahuja T, Roerig DL et al. Coenzyme Q1 redox metabolism during passage through the rat pulmonary circulation and the effect of hyperoxia. Journal of applied physiology (Bethesda, Md. : 1985). 2008; 105(4):1114-26. doi: 10.1152/japplphysiol.00177.2008.
10. Galam L, Failla A, Soundararajan R, Lockey RF, Kolliputi N. 4-hydroxynonenal regulates mitochondrial function in human small airway epithelial cells. Oncotarget. 2015; 6(39):41508-21. doi: 10.18632/oncotarget.6131.
11. Dworski R. Oxidant stress in asthma. Thorax. 2000; 55 Suppl 2(Suppl 2):S51-3. doi: 10.1136/thorax.55.suppl_2.s51.
12. Cho YS, Lee J, Lee TH, Lee EY, Lee KU et al. Alpha-Lipoic acid inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma. The Journal of allergy and clinical immunology. 2004; 114(2):429-35. doi: 10.1016/j.jaci.2004.04.004.
13. Luo ZL, Sun HY, Wu XB, Cheng L, Ren JD. Epigallocatechin-3-gallate attenuates acute pancreatitis induced lung injury by targeting mitochondrial reactive oxygen species triggered NLRP3 inflammasome activation. Food & function. 2021; 12(12):5658-5667. doi: 10.1039/d1fo01154e.
14. Park SK, Hyun SH, In G, Park CK, Kwak YS et al. The antioxidant activities of Korean Red Ginseng (Panax ginseng) and ginsenosides: A systemic review through in vivo and clinical trials. Journal of ginseng research. 2021; 45(1):41-47. doi: 10.1016/j.jgr.2020.09.006.
15. Wei X, Su F, Su X, Hu T, Hu S. Stereospecific antioxidant effects of ginsenoside Rg3 on oxidative stress induced by cyclophosphamide in mice. Fitoterapia. 2012; 83(4):636-42. doi: 10.1016/j.fitote.2012.01.006.
16. Sun M, Ye Y, Xiao L, Duan X, Zhang Y et al. Anticancer effects of ginsenoside Rg3 (Review). International journal of molecular medicine. 2017; 39(3):507-518. doi: 10.3892/ijmm.2017.2857.
17. Lee H, Kong G, Tran Q, Kim C, Park J et al. Relationship Between Ginsenoside Rg3 and Metabolic Syndrome. Frontiers in pharmacology. 2020; 11:130. doi: 10.3389/fphar.2020.00130.
18. Liu X, Zhang Z, Liu J, Wang Y, Zhou Q et al. Ginsenoside Rg3 improves cyclophosphamide-induced immunocompetence in Balb/c mice. International immunopharmacology. 2019; 72:98-111. doi: 10.1016/j.intimp.2019.04.003.
19. Yang J, Li S, Wang L, Du F, Zhou X et al. Ginsenoside Rg3 Attenuates Lipopolysaccharide-Induced Acute Lung Injury via MerTK-Dependent Activation of the PI3K/AKT/mTOR Pathway. Frontiers in pharmacology. 2018; 9:850. doi: 10.3389/fphar.2018.00850.
20. Lee H, Hong Y, Tran Q, Cho H, Kim M et al. A new role for the ginsenoside RG3 in antiaging via mitochondria function in ultraviolet-irradiated human dermal fibroblasts. Journal of ginseng research. 2019; 43(3):431-441. doi: 10.1016/j.jgr.2018.07.003.
21. Han Y, Wang T, Li C, Wang Z, Zhao Y et al. Ginsenoside Rg3 exerts a neuroprotective effect in rotenone-induced Parkinson's disease mice via its anti-oxidative properties. European journal of pharmacology. 2021; 909:174413. doi: 10.1016/j.ejphar.2021.174413.
22. Cheng Z, Zhang M, Ling C, Zhu Y, Ren H et al. Neuroprotective Effects of Ginsenosides against Cerebral Ischemia. Molecules (Basel, Switzerland). 2019; 24(6):1102. doi: 10.3390/molecules24061102.
23. Li L, Wang Y, Guo R, Li S, Ni J et al. Ginsenoside Rg3-loaded, reactive oxygen species-responsive polymeric nanoparticles for alleviating myocardial ischemia-reperfusion injury. Journal of controlled release: official journal of the Controlled Release Society. 2020; 317:259-272.doi: 10.1016/j.jconrel.2019.11.032.
24. He F, Wang J, Liu Y, Wang X, Cai N et al. Xuebijing injection induces anti-inflammatory-like effects and downregulates the expression of TLR4 and NF-κB in lung injury caused by dichlorvos poisoning. Biomedicine & pharmacotherapy. 2018; 106:1404-1411. doi: 10.1016/j.biopha.2018.07.111.
25. Pinton S, Luchese C, Stangherlin EC, Nogueira CW. Acute exposure to diphenyl ditelluride causes oxidative damage in rat lungs. Ecotoxicology and environmental safety. 2011; 74(3):521-6. doi: 10.1016/j.ecoenv.2010.07.031.
26. Wang J, Yu XF, Zhao JJ, Shi SM, Fu L et al. Ginsenoside Rg3 attenuated omethoate-induced lung injury in rats. Human & experimental toxicology. 2016; 35(6):677-84. doi: 10.1177/0960327115597984.
27. Yavuz Y, Kaya E, Yurumez Y, Sahin O, Bas O et al. Technetium-99m diethylenetriaminepentaacetic acid radioaerosol scintigraphy in organophosphate induced pulmonary toxicity: experimental study. Clinical toxicology (Philadelphia, Pa.). 2008; 46(8):711-5. doi: 10.1080/15563650701584111.
28. Du Y, Wang T, Jiang N, Ren RT, Zhao DL et al. Protective effect of sodium aescinate on lung injury induced by methyl parathion. Human & experimental toxicology. 2011; 30(10):1584-91. doi: 10.1177/0960327110393764.
29. Ramalingam M, Huh YJ, Lee YI. The Impairments of α-Synuclein and Mechanistic Target of Rapamycin in Rotenone-Induced SH-SY5Y Cells and Mice Model of Parkinson's Disease. Frontiers in neuroscience. 2019; 13:1028. doi: 10.3389/fnins.2019.01028.
30. Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM et al. Rotenone, paraquat, and Parkinson's disease. Environmental health perspectives. 2011; 119(6):866-72. doi: 10.1289/ehp.1002839.
31. Ahmad T, Mukherjee S, Pattnaik B, Kumar M, Singh S et al. Miro1 regulates intercellular mitochondrial transport & enhances mesenchymal stem cell rescue efficacy. The European Molecular Biology Organization journal. 2014; 33(9):994-1010. doi: 10.1002/embj.201386030.
32. Shaikh NI, Sethi RS. Impairment of apoptosis pathway via Apaf1 downregulation during chlorpyrifos and/or cypermethrin induced lung damage. Animal Biotechnology. 2021:1-8. doi: 10.1080/10495398.2021.1981918.
33. Rahman I, Morrison D, Donaldson K, MacNee W. Systemic oxidative stress in asthma, COPD, and smokers. American journal of respiratory and critical care medicine. 1996; 154(4 Pt 1):1055-60. doi: 10.1164/ajrccm.154.4.8887607.
34. Cortijo J, Martí-Cabrera M, de la Asuncíon JG, Pallardó FV, Esteras A et al. Contraction of human airways by oxidative stress protection by N-acetylcysteine. Free radical biology & medicine. 1999; 27(3-4):392-400. doi: 10.1016/s0891-5849(99)00070-2.
35. Yang H, Lv H, Li H, Ci X, Peng L. Oridonin protects LPS-induced acute lung injury by modulating Nrf2-mediated oxidative stress and Nrf2-independent NLRP3 and NF-κB pathways. Cell communication and signaling: CCS. 2019; 17(1):62. doi: 10.1186/s12964-019-0366-y.
36. Li T, Wu YN, Wang H, Ma JY, Zhai SS et al. Dapk1 improves inflammation, oxidative stress and autophagy in LPS-induced acute lung injury via p38MAPK/NF-κB signaling pathway. Molecular immunology. 2020; 120:13-22. doi: 10.1016/j.molimm.2020.01.014.
37. Jiang JS, Chou HC, Chen CM. Cathelicidin attenuates hyperoxia-induced lung injury by inhibiting oxidative stress in newborn rats. Free radical biology & medicine. 2020; 150:23-29. doi: 10.1016/j.freeradbiomed.2020.02.005.
38. Jenner P. Oxidative stress in Parkinson's disease. Annals of neurology. 2003;53 Suppl 3:S26-36; discussion S36-8. doi: 10.1002/ana.10483.
39. Zhang H, Zheng W, Feng X, Yang F, Qin H et al. Nrf2-ARE Signaling Acts as Master Pathway for the Cellular Antioxidant Activity of Fisetin. Molecules (Basel, Switzerland). 2019; 24(4):708. doi: 10.3390/molecules24040708.
40. Lee YC, Lee KS, Park SJ, Park HS, Lim JS et al. Blockade of airway hyperresponsiveness and inflammation in a murine model of asthma by a prodrug of cysteine, L-2-oxothiazolidine-4-carboxylic acid. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2004; 18(15):1917-9. doi: 10.1096/fj.04-2212fje.
41. Ryoo SM, Lee J, Lee YS, Lee JH, Lim KS et al. Lactate Level Versus Lactate Clearance for Predicting Mortality in Patients With Septic Shock Defined by Sepsis-3. Critical care medicine. 2018; 46(6):e489-e495. doi: 10.1097/CCM.0000000000003030.
Published
How to Cite
Issue
Section
AUTHORS WHO PUBLISH WITH THIS JOURNAL AGREE TO THE FOLLOWING TERMS:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 Unported License. that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
.