Comparison of the efficacy of the various antioxidants against lung damage caused by sulfur mustard and the exposition of their effects on serum parameters
Keywords:Sulphur mustard, oxidative stress, antioxidants, acute toxicity
Aim: In our research on new and previously used agents it is intended to reach proposals to protect and reduce toxic effects of sulfur mustard against lungs. Material-Methods: Approximately 60 SD male rats in the same age and weight were used in our research. One of sulfur mustard group agent the 2-chloroethyl ethyl sulfide (CEES) known as half mustard was used to form the model. CEES in 1 mg / kg dose were applied by the intratracheal way. The study is initiated after creating the groups from experimental animals, sham, control (sulfur mustard), sulfur mustard+N-acetylcysteine, sulfur mustard+lipoic acid, sulfur mustard+mesna and the sulfur mustard+amifostine. After sulfur mustard toxicity model is created, in 15 minutes the therapeutic agents were begun to apply. Treatment was administered for 3 days. After this time the rats were surgically opened under anesthesia applying sternotomy and blood and lung tissue samples were taken for the purpose of serum analysis. Because of histopathological evaluation purposes this tissues are taken into Eppendorfs for 10% formalin, biochemical and ELISA assays and stored at -80°C and appropriate conditions in the refrigerator until the analysis process. Result: Looking at the results of the mortality rate, 60% mortality rate observed in pathological control (SM) group, was observed statistically significant to decrease only in Amifostine and lipoic acid group (respectively viii 10 % and 20% ) In the histopathological evaluation; in routine H & E-stained tissue sections was made a general histopathological evaluation and scoring especially with pulmonary edema, hemorrhage and inflammation evaluations. In the evaluation, it was observed that more intense edema, hemorrhage and inflammation in pathological control group (SM) compared to sham group, decreased significantly only in the group treated with Amifostine and lipoic acid. It was not observed any significant difference between groups comparing in Serum malondialdehyde (MDA) levels showing the level of lipid peroxidation caused by oxidative stress, comparing NOx levels indicating the nitrostatif stress level, the antioxidant enzymes SOD and GPx levels indicating antioxidant defense level and neopiter levels accepted as one of inflammation criteria. Conclusion: As a result, in the light of the data obtained, it needs to be tested in a more appropriate model, whether serum MDA, SOD, GPx, NOx, as Neopterin oxido- nitrosative , antioxidant parameters would be used for condition detection and monitoring in acute lung toxicity. Besides new antioxidants such as Amifostine and α-lipoic acid has been shown to have promising hope in treatment of acute lung toxicity caused by sulfur mustard.
Cooper G, Rice P, Greaves I. Chemical casualties-special issue. J R Army Med Corps 2002;4:328-404.
Khateri S, Wangerin R. Denied Truths. The center for Women and Family Affairs:Tehran. 2008.
Davison C, Rozman RS, Smith PK. Metabolism of bis-bβ-chloroethyl sulfide (sulfur mustard gas). Biochem Pharmacol.1961;7:65–74.
Ghabili K, Agutter PS, Ghanei M, Ansarin K, Shoja MM. Mustard gas toxicity: The acute and chronic pathological effects. J Appl Toxicol. 2010;30:627–643.
Erdelyi K, Bakondi E, Gergely P, Szabo C, Virag L. Pathophysiologic role of oxidative stress-induced poly (ADP-ribose) polymerase-1 activation: focus on cell death and transcriptional regulation. Cell Mol Life Sci. 2005;62:751–759.
Saladi RN, Smith E, Persaud AN. Mustard; a potential agent of chemical warfare and terrorism.Clin Exp Dermatol. 2006;31(1):1-5.
Hosseini K, Moradi K, Mansouri A, Vessal K.Pulmonary manifestions of mustard gas injury: a review of 61 cases.Iran.J.Med.Sci.1989;14:20-26.
Dahl AR. Contemporary issues in toxicology. Toxicol. Appl. Pharmacol. 1990;103:185-197.
Foroutan SA. Medical notes on chemical warfare, part II (in persian). Kowsar Med J.1997;1:159-177.
Greenfield RA, Brown BR, Hutchins JB, et al. Microbiological,biological, and chemical weapons of warfare and terrorism.J.Appl.Toxicol.2002; 22:257-262.
Easton D, Peto J, Doll R. Cancers of the respisıçanory tract in mustard gas workers. Br J Ind Med. 1988;45:652–659.
Kehe K, Szinicz L. Medical aspects of sulphur mustard poisoning. Toxicology. 2005;214(3):198–209.
Rappenau S, Baeza-Squbian A, Braut-Boucher F, Aubery M,Gendorm MC, Marano F. Use of fluorescent probes to assess the early sulfhydryl depletion and oxidative stress induced by mechlorethamine on airway epithelium. Toxicol In Vitro.1999;13:765–771.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin-phenol reagent. J Biol Chem. 1951;193:265-275.
Okhawa H, Ohshi N, Yagi K. Assay or lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95:351-358.
Sun Y, Oberley LW, Ying L. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34:497-500.
Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterisation of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967; 70: 158-169.
Akgül EÖ, Aydın İ, Çaycı T, Kurt YG, Aydın FN, Ağıllı M. The indicator of cellular immune response in body fluids: neopterin. Gulhane Med J. 2013; 55(3):237-243.
Alrashed M, Abougoush M, Akgul EO, Erbil MK. Detection method of serum and urine neopterin levels by high performance liquid chromatography. Gulhane Med J. 2002;44:273e7.
Bismuth C, Borron SW, Baud FJ, Barriot P. Chemical weapons: documented use and compounds on the horizon. Toxicol Lett. 2004;149:11–18.
Ghazanfari T, Faghihzadeh S, Aragizadeh H, et al. Sardasht-Iran cohort study of chemical warfare victims: design and methods (J). Arch Iran Med. 2009; 12(1):5-14.
Balali-Mood M, Navaeian A. Clinical and paraclinical findings in 233 patients with sulphur mustard poisoninig, in: Heyndricks B. (Ed.), Proceedings of the Second World Congress on New Compounds in Biological and Chemical Warfare, Rijksuniversiteit, Ghent, Belgium. 1986;464-473.
Ucar M, Korkmaz A, Reiter RJ, et al. Melatonin alleviates lung damage induced by the chemical warfare agent nitrogen mustard. Toxicol Lett. 2007;173:124–131.
Chatterjee D, Mukherjee S, Smith MG, Das SK. Signal transduction events in lung injury induced by 2-chloroethyl ethyl sulfide, a mustard analog. Journal of Biochemical and Molecular Toxicology. 2003;17(2):114-121.
Laskin DL, Gardner CR, Laskin JD. Phagocytes, In:Lawrence,D. (Ed), Comprehensive Toxicology, 2nd edition.: Immune System Toxicology, vol.5. Elsevier, UK. 2010;133-153.
Beckman JS, Crow JP. Pathological ımplications of nitric oxide, superoxide and peroxynitrite formation. Biochemical Society Transactions. 1993;21:330-334.
Di Ilio C, Sacchetta P, Del Boccio G, La Rovere G, Federici G. Glutathione peroxidase, glutathione s-transferase and glutathione reductase activities in normal and neoplastic human breast tissue. Cancer Letters. 1985; 29: 37-42.
Fridovich I. Superoxide radical: an endogenous toxicant. Ann Rev Toxicol. 1983;23:239-257.
Sugiyama M. Role of cellular antioxidants in metal-induced damage. Cell Biology and Toxicology. 1994;10:1-22.
De Rosa S, Cirillo P, Pacileo M, et al. Neopterin: from forgotten biomarker to leading actor in cardiovascular pathophysiology. Curr Vasc Pharmacol. 2011;9:188–199.
Murr C, Fuith LC, Widner B, Wirleitner B, Baier-Bitterlich G, Fuchs D. Increased neopterin concentrations in patients with cancer: indicator of oxidative stress? Anticancer Res. 1999; 19:1721–1728.
Jenny M, Klieber M, Zaknun D, et al. In vitro testing for anti-inflammatory properties of compounds employing peripheral blood mononuclear cells freshly isolated from healthy donors. Inflamm Res. 2011;60:127–135.
Topal T, Oztas Y, Korkmaz A, et al. Melatonin ameliorates bladder damage induced by cyclophosphamide in rats. J Pineal Res. 2005;38:272–277.
Korkmaz A, Oter S, Sadir S, et al. Peroxynitrite may be involved in bladder damage caused by cyclophosphamide in rats. J Urol. 2005;173:1793–1796.
Korkmaz A, Yaren H, Topal T, Oter S. Molecular targets against mustard toxicity: implication of cell surface receptors, peroxynitrite production, and PARP activation. Arch Toxicol. 2006; 80: 662–670.
Koukourakis MI. Amifostine in clinical oncology: current use and future applications. Anticancer Drugs. 2002;13:181–209.
Culy CR, Spencer CM. Amifostine: An update on its clinical status as a cytoprotectant in patients with cancer receiving chemotherapy or radiotherapy and its potential the rapeutic application in myelodysplastic syndrome. Drugs. 2001;61:641–684.
Gautam A, Vijayaraghavan R. Drde-07: a possible antidote for sulphur mustard toxicity. Cell Mol Biol (Noisy-le-grand). 2010;56 Suppl:OL1334-40.
Sawale SD, Ambhore PD, Pawar PP, Pathak U, Deb U, Satpute RM. Ameliorating effect of S-2(ω-aminoalkylamino) alkylaryl sulfide (DRDE-07) on sulfur mustard analogue, 2-chloroethyl ethyl sulfide-induced oxidative stress and inflammation. Toxicol Mech Methods. 2013;23(9):702-710.
Anand T, Vijayaraghavan R, Rao PV, Bansal I, Bhattacharya BK. Attenuation of sulfur mustard toxicity by S-2(2-aminoethylamino)ethyl phenyl sulfide (DRDE-07) in mouse liver. Toxicol Mech Methods. 2011;21(8):596-605.
Gautam A, Gupta A, Lomash V, Pant SC, Vijayaraghavan R. Prophylactic efficacy of combination of DRDE-07 and its analogues with amifostine against sulphur mustard induced systemic toxicity. Indian J Exp Biol. 2010;48(7):752-61.
Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and the rapeutic potential. Biochim Biophys Acta. 2009;1790:1149–1160.
Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med 1995; 19: 227–250
Suzuki YJ, Tsuchiya M, Packer L. Antioxidant activities of dihydrolipoic acid and its structural homologues. Free Radic Res Commun. 1993;18:115–122.
Kehrer JP, Biswal SS. Themoleculareffects of acrolein.Toxicol Sci. 2000;57:6–15.
Goren MP, McKenna LM, Goodman TL. Combined intravenous and oral mesna in outpatient streated with ifosfamide. Cancer Chemother Pharmacol. 1997;40:371–375.
Kurovski V, Wagner T. Urinary excretion of ifosfamide, 4-hydroxyfosfamide, 3- and 2-dechloroethyl ifosfamide, mesna, and di mesna in patients on fractionated intravenous ifosfamide and concomitant mesna therapy. Cancer Chemother Pharmacol. 1997;39:431–439.
Ventresca GP, Cicchetti V, Ferrari V. Acetylcysteine.In: Braga PC, Allegra L, eds. Drugs in bronchial muco1ogy.New York, RavenPress 1989;77-102.
Aruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide and hypochlorous acid. Free Rad Bioi Med. 1989;6:593-597.
Weinberger B, Laskin JD, Sunil VR, Sinko PJ, Heck DE, Laskin DL. Sulfur mustard-induced pulmonary injury: therapeutic approaches to mitigating toxicity. Pulm Pharmacol Ther. 2011;24(1):92-99.
How to Cite
Copyright (c) 2023 Journal of Social and Analytical Health
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.