The Healing Effect of Resveratrol on Ischemic Tissue Injury in an Experimental Carbon Monoxide Poisoning Model

Abstract

Purpose: To investigate the healing effect of resveratrol on ischemia, inflammation and oxidative injury in brain and heart tissue of rats in an experimentally induced carbonmonoxide CO intoxication model. Methods: Twenty-eight mature female Spraque Dawley rats were randomized into four groups of seven animals each. Groups I and II inhaled room air for 60 minutes. Groups III and IV inhaled a high concentration of a 5000 ppm CO gas mixture at 4 L/min until loss of consciousness. Blood CO levels were measured from 1 mL blood specimens collected from the tail vein. Groups I and III received 1 mL of normal saline while groups II and IV received 25 mg/kg resveratrol intraperitoneally. At the end of 48 hour, the rats were sacrified and later blood, brain and heart tissue samples were taken for histopathological and biochemical evaluation. Neuron damage scores, percentages of degenerate neurons and apoptosis rates in the cortex and hypothalamus were calculated in brain tissues. Myocyte degeneration, vascular congestion and myocyte apoptosis rates were calculated in heart tissues. Total antioxidant TAS , total oxidant TOS and oxidative stress index OSI levels were also calculated from the tissue samples. Results: Histopathological evaluation revealed that resveratrol significantly reduced tissue damage in the brain when groups III and IV were compared p

Keywords

• CO poisoning, resveratrol, brain, heart

References

1. 1. Bojakowski K, Gaciong Z, Grochowiecki T, Szmidt J. Carbon Monoxide May Reduce Ischemia Reperfusion Injury: A Case Report of Complicated Kidney Transplantation From a Carbon Monoxide Poisoned Donor. Transplant Proc 2007;39:2928–2929. [CrossRef]
2. 2. Gorman DF. Carbon monoxide: From toxic poison to brain messenger. S Pac Underwater Med Soc J 1995;25:77. https://scholar.google.com/ scholar?cluster=13806997695340807464&hl=tr&as_sdt=0,5
3. 3. Chiew AL, Buckley NA. Carbon monoxide poisoning in the 21st century. Crit Care Med 2014;18:221. https://doi.org/10.1186/cc13846
4. 4. Tomaszewski C. Carbon Monoxide. In: Goldfrank’s Toxicologic Emergencies, 8th ed. Flomenbaum NE, Goldfrank LR, Hoffman R, Howland MA, Lewin NA, Nelson LS, editors. New York: Mc Graw-Hill; 2006.
5. 5. Roderique JD, Josef CS, Feldman MJ, Spiess BD. A modern literature review of carbon monoxide poisoning theories, therapies, and potential targets for therapy advancement. Toxicology 2015;334:45– 58. [CrossRef]
6. 6. Hampson NB, Hauff NM. Risk factors for short-term mortality from carbon monoxide poisoning treated with hyperbaric oxygen. Crit Care Med 2008;36:2523–2527. [CrossRef]
7. 7. Jardim FR, de Rossi FT, Nascimento MX, et al. Resveratrol and Brain Mitochondria: a Review. Mol Neurobiol 2018;55:2085–2101. [CrossRef]
8. 8. Soleas GJ, Diamandis EP, Goldberg DM. Resveratrol: a molecule whose time has come? And gone? Clin Biochem 1997;30:91–113. [CrossRef]

9. 9. Bonnefont-Rousselot D. Resveratrol and Cardiovascular Diseases. Nutrients 2016;8:250. [CrossRef]
10. 10. Turedi S, Yilmaz SE, Mentese A, et al. The diagnostic value of serum ischemia-modified albumin levels in experimentally induced carbon monoxide poisoning and their correlation with poisoning severity. Acad Emerg Med 2013;20:652–658. [CrossRef]
11. 11. Kim J, Shin W. How to Do Random Allocation (Randomization). Clin Orthop Surg 2014;6:103–109. [CrossRef]
12. 12. Chavez E, Reyes-Gordillo K, Segovia J, et al. Resveratrol prevents fibrosis, NF-kappaB activation and TGF-beta increases induced by chronic CCl4 treatment in rats. J Appl Toxicol 2008;28:35–43. [CrossRef]
13. 13. Yulug E, Turedi S, Karaguzel E, Kutlu O, Mentese A, Alver A. The short term effects of resveratrol on ischemia-reperfusion injury in rat testis. J Pediatr Surg 2014;49:484–489. [CrossRef]
14. 14. Garman RH. Histology of the central nervous system. Toxicol Pathol 2011;39:22–35. [CrossRef]
15. 15. Kesim M, Yulug E, Kadioglu M, et al. The effect of simvastatin on picrotoxin-induced seizure in mice. J Pak Med Assoc 2012;62:1187– 1191. https://jpma.org.pk/article-details/3800?article_id=3800
16. 16. Tokatli F, Uzal C, Doganay L, et al. The potential cardioprotective effects of amifostine in irradiated rats. Int J Radiat Oncol Biol Phys 2004;58:1228–1234. [CrossRef]
17. 17. Chang JE, Kim HJ, Jheon S, Lim C. Protective effects of GV1001 on myocardial ischemiareperfusion injury. Mol Med Rep 2017;16:7315– 7320. [CrossRef]
18. 18. Hu Huang SS, Tsai MC, Chih CL, Hung LM, Tsai SK. Resveratrol reduction of infarct size in Long-Evans rats subjected to focal cerebral ischemia. Life Sci 2001;69:1057–1065. [CrossRef]
19. 19. Weaver LK. Carbon monoxide poisoning. New Engl J Med 2009;360:1217–1225. [CrossRef]
20. 20. Wang P, Zeng T, Zhang CL, et al. Lipid peroxidation was involved in the memory impairment of carbon monoxide induced delayed neuron damage. Neurochem Res 2009;34:1293–1298. [CrossRef]
21. 21. Satran D, Henry CR, Adkinson C, Nicholson CI, Bracha Y, Henry TD. Cardiovascular manifestations of moderate to severe carbon monoxide poisoning. J Am Coll Cardiol 2005;45:1513–1516. [CrossRef]
22. 22. Pineda-Ramirez N, Gutierrez Aguilar GF, Espinoza-Rojo M, Aguilera P. Current evidence for AMPK activation involvement on resveratrolinduced neuroprotection in cerebral ischemia. Nutr Neurosci 2018;21:229–247. [CrossRef]
23. 23. Gocmez SS, Sahin TD, Yazir Y, et al. Resveratrol prevents cognitive deficits by attenuating oxidative damage and inflammation in rat model of streptozotocin diabetes induced vascular dementia. Physiol Behav 2019;201:198–207. [CrossRef]
24. 24. Andrade S, Ramalho MJ, Carmo Pereira MD, Loureiro JA. Resveratrol Brain Delivery for Neurological Disorders Prevention and Treatment. Front Pharmacol 2018;9:1261. [CrossRef]
25. 25. Tabrizian K, Shahraki J, Bazzi M, Rezaee R, Jahantigh H, Hashemzaei M. Neuro-Protective Effects of Resveratrol on Carbon MonoxideInduced Toxicity in Male Rats. Phytother Res 2017;31:1310–1315. [CrossRef]
26. 26. Rezaee MA, Mohammadpour AH, Imenshahidi M, et al. Protective effect of erythropoietin on myocardial apoptosis in rats exposed to carbon monoxide. Life Sci 2016;148:118–124. [CrossRef]
27. 27. Hashemzaei M, Barani AK, Iranshahi M, et al. Effects of resveratrol on carbon monoxide-induced cardiotoxicity in rats. Environ Toxicol Pharmacol 2016;46:110–115. [CrossRef]
28. 28. Lin J-F, Lin S-M, Chih C-L, et al. Resveratrol reduces infarct size and improves ventricular function after myocardial ischemia in rats. Life Sci 2008;83:313–317. [CrossRef]
29. 29. Bastianetto S, Ménard C, Quirion R. Neuroprotective action of resveratrol. Biochim Biophys Acta 2015;1852:1195–1201. [CrossRef]
30. 30. Wang W, Li Y, Ren J, Xia F, Li J, Zhang Z. Hydrogen rich saline reduces immunemediated brain injury in rats with acute carbon monoxide poisoning. Neurol Res 2012;34:1007–1015. [CrossRef]
31. 31. Kekec Z, Seydaoglul G, Sever H, Ozturk F. The effect of antioxidants (N-acetylcysteine and melatonin) on hypoxia due to carbonmonoxide poisoning. Bratisl Lek Listy 2010;111:189–193. https://pubmed.ncbi. nlm.nih.gov/20586144/
32. 32. Fenwick N, Griffin G, Gauthier C. The welfare of animals used in science: how the “Three Rs” ethic guides improvements. Can Vet J 2009;50:523–530. https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2671878/