Determination The Effective Dose of Sodium Thiosulfate in Adult Rats Treated with Nicotine
DOI:
https://doi.org/10.30526/38.2.3645Keywords:
Sodium thiosulfate, effective dose, MDA, Blood, Partial pressure, oxygenAbstract
Sodium thiosulfate (STS) is a possible therapeutic candidate molecule in a range of diseases and drug-induced toxicities due to its antioxidant, anti-inflammatory, and anti-apoptotic capabilities. The current study aimed to find the effective dose of STS in adult male rats given nicotine by evaluating serum MDA and blood partial pressure of oxygen (PO2) levels. Thirty-six adult male Wistar rats, Rattus norvegicus (weighing 190–220 g) with an age of 3–3.5 months, were chosen randomly and separated into six equal groups, administered for 28 days. Animals in the control group were administered an intraperitoneal (i.p.) injection of normal saline, while those in groups 1, 2, 3, 4, and 5 received repeated doses of an i.p. nicotine injection of 1.5 mg/kg b.w. One hour later, they were i.p. injected with 150, 250, 350, 450, and 550 mg/kg b.w. of STS, respectively. Both medications continued to be given for a period of 28 days. At the end of the experiment, serum malondialdehyde (MDA) and PO2 were measured. Results showed a negative relationship between blood PO2 concentration and five successive doses of sodium thiosulfate, but a positive linear relationship among successive doses of sodium thiosulfate on serum MDA concentration was observed. The estimated amount of sodium thiosulfate that caused a considerable decrease in serum MDA levels and a rise in blood PO2 was found to be 450 mg/kg bw. The current study's findings show that different doses of sodium thiosulfate can significantly reduce the harmful effects of nicotine exposure by reducing the formation of oxidative stress and the detrimental effects on respiratory function, which are characterized by an increase in blood PO2 levels.
References
1. Zhang MY, Dugbartey GJ, Juriasingani S, Sener A. Hydrogen sulfide metabolite, sodium thiosulfate: Clinical applications and underlying molecular mechanisms. Int J Mol Sci. 2021;22(12):6452. https://doi.org/10.3390/ijms22126452.
2. Ravindran S, Boovarahan SR, Shanmugam K, Vedarathinam RC, Kurian GA. Sodium thiosulfate preconditioning ameliorates ischemia/reperfusion injury in rat hearts via reduction of oxidative stress and apoptosis. Cardiovasc Drugs Ther. 2017;31(5):511–24. https://doi.org/10.1007/s10557-017-6743-4.
3. Yang X, Liu Y, Xie X, Shi W, Si J, Li X. Use of the optimized sodium thiosulfate regimen for the treatment of calciphylaxis in Chinese patients. Ren Fail. 2022;44(1):914–22. https://doi.org/10.1080/0886022X.2022.2078462.
4. Grover P, Khanna K, Bhatnagar A, Purkayastha J. In vivo-wound healing studies of sodium thiosulfate gel in rats. Biomed Pharmacother. 2021;140:111797. https://doi.org/10.1016/j.biopha.2021.111797
5. Hayden MR, Tyagi SC, Kolb L, Sowers JR, Khanna R. Vascular ossification–calcification in metabolic syndrome, type 2 diabetes mellitus, chronic kidney disease, and calciphylaxis–calcific uremic arteriolopathy: the emerging role of sodium thiosulfate. Cardiovasc Diabetol. 2005;4(1):1–22. https://doi.org/10.1186/1475-2840-4-4.
6. Shekari M, Gortany NK, Khalilzadeh M, Abdollahi A, Ghafari H, Dehpour AR. Cardioprotective effects of sodium thiosulfate against doxorubicin-induced cardiotoxicity in male rats. BMC Pharmacol Toxicol. 2022;23(1):32. https://doi.org/10.1186/s40360-022-00566-z.
7. Ascar IF, Khaleel FM, Hameed AS, Alabboodi MK. Evaluation of Some Antioxidants and Oxidative Stress Tests in Iraqi Lung Cancer Patients. Baghdad Sci J. 2022;19(6 Suppl.):1466. https://doi.org/10.21123/bsj.2022.7597.
8. Alqayim MA. Antiatherogenic effects of Vitamin E against lead acetate induced hyperlipidemia. Mesop Environ J. 2015;1(2):85–95. https://www.iraqoaj.net/iasj/download/4435b6a407082e83.
9. Ito H, Yamashita Y, Tanaka T, Takaki M, Le MN, Yoshida L-M. Cigarette smoke induces endoplasmic reticulum stress and suppresses efferocytosis through the activation of RhoA. Sci Rep. 2020;10(1):12620. https://doi.org/10.1038/s41598-020-69282-3.
10. Thimmulappa RK, Chattopadhyay I, Rajasekaran S. Oxidative stress mechanisms in the pathogenesis of environmental lung diseases. In: Oxidative Stress in Lung Diseases. Springer; 2020. p. 103–37. https://doi.org/10.1007/978-981-32-9366-3_5.
11. Hamady JJ, Al-Okaily BN. Alveolar gene expression of tight junction protein in nicotine rats treated with zinc and vitamin D. Int J Health Sci (Qassim). 2022;6:232–46. https://doi.org/10.53730/ijhs.v6nS9.12218.
12. Maurya PK, Dua K. Role of oxidative stress in pathophysiology of diseases. In: Role Oxidative Stress Pathophysiology Disease; 2020: p. 1–297. https://doi.org/10.1007/978-981-15-1568-2.
13. Nawfal AJ, Al-Okaily BN. Effect of the Sublethal Dose of Lead Acetate on Malondialdehyde, Dopamine, and Neuroglobin Concentrations in Rats. Worlds Vet J. 2022;12(3):311–5. http://dx.doi.org/10.54203/scil.2022.wvj39.
14. Wooten JB, Chouchane S, McGrath TE. Tobacco smoke constituents affecting oxidative stress. In: Cigar Smoke Oxidative Stress; 2006: p. 5-46. http://dx.doi.org/10.1007/3-540-32232-9_2.
15. Horinouchi T, Higashi T, Mazaki Y, Miwa S. Carbonyl compounds in the gas phase of cigarette mainstream smoke and their pharmacological properties. Biol Pharm Bull. 2016;39(6):909–14. https://doi.org/10.1248/bpb.b16-00025.
16. Caliri AW, Tommasi S, Besaratinia A. Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer. Mutat Res Mutat Res. 2021;787:108365. https://doi.org/10.1016/j.mrfmmm.2021.108365.
17. Mohammed B, Al-Thwani A. Evaluation the effect of nicotine injection on the lungs of mice. J Reports Pharm Sci. 2019;8(1):34–8. https://doi.org/10.4103/jrptps.jrptps_28_18.
18. Hiremagalur B, Nankova B, Nitahara J, Zeman R, Sabban EL. Nicotine increases expression of tyrosine hydroxylase gene. J Biol Chem. 1993;268(31):23704–11. https://pubmed.ncbi.nlm.nih.gov/7901211/.
19. Arabaci Ü, Akdur H, Yigit Z. Effects of smoking on pulmonary functions and arterial blood gases following coronary artery surgery in Turkish patients. Jpn Heart J. 2003;44(1):61–72. https://doi.org/10.1536/jhj.44.61.
20. Socol ML, Manning FA, Murata Y, Druzin ML. Maternal smoking causes fetal hypoxia: experimental evidence. Am J Obstet Gynecol. 1982;142(2):214–8. https://doi.org/10.1016/s0002-9378(16)32339-0.
21. Lykkesfeldt J. Malondialdehyde as biomarker of oxidative damage to lipids caused by smoking. Clin Chim Acta. 2007;380(1–2):50–8. https://doi.org/10.1016/j.cca.2007.01.028.
22. Hamady JJ, Al-Okaily BN. Anti-inflammatory and antioxidant effects of zinc and vitamin D on nicotine-induced oxidative stress in adult male rats. Int J Health Sci (Qassim). 2022;6(June):73–91. https://doi.org/10.53730/ijhs.v6nS9.12171.
23. Guidet B, Shah SV. Enhanced in vivo H2O2 generation by rat kidney in glycerol-induced renal failure. Am J Physiol Physiol. 1989;257(3):F440–5. https://doi.org/10.1152/ajprenal.1989.257.3.f440.
24. Snedecor GW, Cochran WG. Statistical methods, 6th Edition. The Iowa State University Press; 1980. p. 238–48.
25. Raeeszadeh M, Beheshtipour J, Jamali R, Akbari A. The antioxidant properties of Alfalfa (Medicago sativa L.) in nicotine-induced oxidative stress in the rat liver. Oxid Med Cell Longev. 2022;2022: 2691577. https://doi.org/10.1155/2022/2691577.
26. Oyeyipo IP, Raji Y, Bolarinwa AF. Nicotine alters serum antioxidant profile in male albino rats. N Am J Med Sci. 2014;6(4):168. https://doi.org/10.4103/1947-2714.131240.
27. Hamza RZ, El-Shenawy NS. Anti-inflammatory and antioxidant role of resveratrol on nicotine-induced lung changes in male rats. Toxicol Reports. 2017;4:399–407. http://dx.doi.org/10.1016/j.toxrep.2017.07.003.
28. Khudair NT, Al-Okaily BN. Renal ameliorating effect of resveratrol in hydrogen peroxide induced male rats. Iraqi J Vet Sci. 2022;36(3):571–7. https://doi.org/10.33899/ijvs.2022.132149.2193.
29. Schulz J, Kramer S, Kanatli Y, Kuebart A, Bauer I, Picker O. Sodium thiosulfate improves intestinal and hepatic microcirculation without affecting mitochondrial function in experimental sepsis. Front Immunol. 2021;12:671935. https://doi.org/10.3389/fimmu.2021.671935.
30. Sanchez-Aranguren L, Grubliauskiene M, Shokr H, Balakrishnan P, Wang K, Ahmad S. Sodium Thiosulphate-Loaded Liposomes Control Hydrogen Sulphide Release and Retain Its Biological Properties in Hypoxia-like Environment. Antioxidants. 2022;11(11):2092. https://doi.org/10.3390/antiox11112092.
31. Ascar IF, Khaleel FM, Hameed AS, Alabboodi MK. Evaluation of Some Antioxidants and Oxidative Stress Tests in Iraqi Lung Cancer Patients. Baghdad Sci J. 2022;19(6 Suppl.):1466. https://doi.org/10.21123/bsj.2022.19.6.Suppl.1466.
32. De Koning MSLY, Assa S, Maagdenberg CG, Van Veldhuisen DJ, Pasch A, Van Goor H. Safety and Tolerability of Sodium Thiosulfate in Patients with an Acute Coronary Syndrome Undergoing Coronary Angiography: A Dose-Escalation Safety Pilot Study (SAFE-ACS). J Interv Cardiol. 2020;2020. https://doi.org/10.1155/2020/8832803.
33. McGeer P. Medical uses of Sodium thiosulfate. J Neurol Neuromedicine. 2016;1(3):28–30. https://doi.org/10.29245/2572.942X/2016/3.1094.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Ibn AL-Haitham Journal For Pure and Applied Sciences

This work is licensed under a Creative Commons Attribution 4.0 International License.
licenseTerms