Vitamin C modulates adrenaline-augmented gastric injury via cardiac troponin/creatine kinase pathway in Wistar rats

Document Type : Original Article

Authors

1 Department of Physiology, College of Medical Sciences, University of Calabar, Calabar Cross River State, Nigeria

2 Department of Physiology, PAMO University of Medical Sciences, Port Harcourt, Rivers State,Nigeria

10.22038/ijbms.2023.68651.15019

Abstract

Objective(s): Vitamin C has anti-oxidant benefits in the gastrointestinal tract and heart. This study investigated the effect of vitamin C on some gastric parameters in myocardial injury in rats. 
Materials and Methods: Thirty Wistar rats were divided into five groups (n = 6). Group 1 was the control and Group 2 (ADR) received 1 mg/kg of adrenaline subcutaneously on days 13 and 14. Group 3 received vitamin C (200 mg/kg) orally for 14 days. Group 4 received adrenaline (1 mg/kg) on days 1 and 2 and vitamin C from days 1 to 14. Group 5 received vitamin C till day 14 and adrenaline on days 13 and 14. All animals were sacrificed after 2 hr of pyloric ligation. Gastric secretion parameters were assessed while a blood sample was obtained for biochemical analysis. 
Results: Gastric juice volume, total gastric acidity, pepsin activity, cardiac troponin 1, creatine kinase-MB, and lactate dehydrogenase levels increased (P<0.05) in ADR only group relative to the control. Pre- and post-vitamin C treatment reduced (P<0.05) these markers to near normal. However, treatment with vitamin C reduced (P<0.05) ulcer score, and increased (P<0.05) pepsin activity, mucus weight, and serum vitamin C levels when compared with the ADR-only group. Pre-treatment with vitamin C resulted in a marked decrease (P<0.05) in gastric juice volume, pepsin activity, and total gastric acidity compared with post-treatment in the adrenaline-induced injury group.
Conclusion: Vitamin C pretreatment reduces excessive gastric secretions, ulcer scores, and attenuates cardio-inflammatory responses in adrenaline-augmented myocardial injury in rats.

Keywords

Main Subjects


1. Liu Y, Wang LF, Liu LH, Yang XC, Ren ZH, Li KB, et al. Impact of prior digestive system disease on in-hospital gastrointestinal bleeding in patients with acute myocardial infarction. Risk Manag Healthc Policy 2021; 14: 1233-1239. 
2. Abe T, Samuel I, Eferoro E, Samuel AO, Monday IT, Olunu E, et al. The diagnostic challenges associated with type 2 myocardial infarction. Int. J Applied Basic Med Res 2021;11:131-138. 
3. Sabatine MS, Bergmark BA, Murphy SA, O’Gara PT, Smith PK, Serruys PW, et al. Percutaneous coronary intervention with drug-eluting stents versus coronary artery bypass grafting in left main coronary artery disease: An individual patient data meta-analysis. Lancet 2021; 398: 2247-2257. 
4. Bermudez-Gonzalez JL, Sanchez-Quintero D, Proaño-Bernal L, Santana-Apreza R, Jimenez-Chavarria MA, Luna-Alvarez-Amezquita JA, et al. Role of the anti-oxidant activity of melatonin in myocardial ischemia-reperfusion injury. Anti-oxidants (Basel) 2022;11:627-647.
5. Chen X, Li X, Xu X, Li L, Liang N, Zhang L, et al. Ferroptosis and cardiovascular disease: Role of free radical-induced lipid peroxidation. Free Rad Res 2021; 55: 405-415.
6. Harjola VP, Mullens W, Banaszewski M, Bauersachs J, Brunner La Rocca H, Chioncel O, et al. Organ dysfunction, injury and failure in acute heart failure: From pathophysiology to diagnosis and management. A review on behalf of the acute heart failure committee of the heart failure association (HFA) of the european society of cardiology (ESC). Eur J Heart Failure 2017; 19: 821-836. 
7. Gesualdo M, Scicchitano PK, Carbonara S, Ricci G, Principi M, Lerardi E, et al. The association between cardiac and gastrointestinal disorders: causal or casual link? J Cardiovasc Med (Hagerstown) 2016; 17: 330-338. 
8. Cowled P, Fitridge R. Pathophysiology of Reperfusion Injury. In: Fitridge, R. (eds) Mechanisms of Vascular Disease. 2020; Springer, Cham. 
9. Wu R, Li J, Guo Y. Treatment of acute upper gastrointestinal bleeding occurred aftern percutaneous coronary intervention for acute myocardial infarction in patients with acute renal impairment: A case report. Cardiovasc Endocrinol Metab 2022; 11: e0269-e0273.
10. Chung J, Rajala J, Moroz D, Zhu Q, Stamm M, Sandha GS. Acetylsalicyclic acid use in patients with acute myocardial infarction and peptic ulcer bleeding. Can J Gastroenterol 2009; 23: 619-623. 
11. Duerksen DR. Stress-related mucosal disease in critically ill patients. Best Pract Res Clin Gastroenterol 2003; 17: 327-344. 
12. Sipponen P, Maaroos HI. Chronic gastritis. J Gastroenterol 2015; 50: 657-667. 
13. Elseweidy MM. Brief review on the causes, diagnosis and therapeutic treatment of gastritis disease. Altern Integr Med 2017; 6: 1-6. 
14. Sanches E, Timmermans M, Topal B, Celik A, Sundbom M, Ribeiro R, et al. Cardiac remodeling in obesity and after bariatric and metabolic surgery; is there a role for gastro-intestinal hormones? Expert Rev Cardiovasc Ther 2019; 17: 771-790. 
15. Zhou X, Li J, Guo J, Geng B, Ji W, Zhao Q, et al. Gut-dependent microbial translocation induces inflammation and cardiovascular events after ST-elevation myocardial infarction. Microbiome 2018; 6: 1-17. 
16. Santos JRU, Brofferio A, Viana B, Pacak K. Catecholamine-induced cardiomyopathy in pheochromocytoma: How to manage a rare complication in a rare disease? Horm Metab Res 2019; 51: 458-469. 
17. Kim H, Bae S, Kim YK, Cho CH, Kim SJ, Kim YJ, et al. Vitamin C prevents stress-induced damage on the heart caused by the death of cardiomyocytes, through down-regulation of the excessive production of catecholamine, TNGF-a, and ROS production in Gulo (-/-) Vit C-insufficient mice. Free Radic Biol Med 2013; 65: 573-583. 
18. El-Marasy SA, El Awdan SA, Hassan A, Abdallah HM. Cardioprotective effect of thymol against adrenaline-induced myocardial injury in rats. Heliyon 2020; 6: e04431-e04438. 
19. Lyu J, Wang M, Kang X, Xu H, Cao Z, Yu T, et al. Macrophage mediated regulation of catecholamines in sympathetic neural remodeling after myocardial infarction. Basic Res Cardiol 2020; 115: 56-70. 
20. Sinha N, Dabla PK. Oxidative stress and anti-oxidants in hypertension–a current review. Curr Hyperten Rev 2015;11:132-142. 
21. Aguirre R, May JM. Inflammation in the vascular bed: Importance of vitamin C. Pharmacol Ther 2008;119:96-103. 
22. Siti HN, Kamisah Y, Kamsiah JJVP. The role of oxidative stress, anti-oxidants and vascular inflammation in cardiovascular disease (a review). Vasc Pharmacol 2015; 71:40-56. 
23. Ghafarifarsani H, Hoseinifar SH, Javahery S, Yazici M, Van Doan H. Growth performance, biochemical parameters, and digestive enzymes in common carp (Cyprinus carpio) fed experimental diets supplemented with vitamin C, thyme essential oil, and quercetin. Italian J Anim Sci 2022; 21: 291-302. 
24. Aziz FTA, Sanad FAA, Temraz A, El-Tantawy WH, Hassan MA. Study of cardioprotective activity of the methanolic extract of the aerial parts of Bauhinia madagascariensis compared to Bauhinia purpurea against adrenaline-induced myocardial toxicity in rats. Drug Chem Toxicol 2022; 45:2341-2351.
25. Owu DU, Nwokocha CR, Ikpi DE, Ogar EI. Effect of vitamin C supplementation on platelet aggregation and serum electrolytes levels in streptozotocin-induced diabetes mellitus in rats. Niger J Physiol Sci 2016;31:55-61. 
26. Koike T, Ohara S, Sekine H, Iijima L, Abe Y, Kato K, et al. Helicobacter pylori infection prevents erosive reflux oesophagitis by decreasing gastric acid secretion. Gut 2001; 49: 319-320. 
27. Lee JK, Jung SH, Lee SE, Han JH, Jo E, Park HS, et al. Alleviation of ascorbic acid-induced gastric high acidity by calcium ascorbate in vitro and in vivo. Korean J Physiol Pharmacol 2018; 22:35-42.
28. Tan PV, Enow-Orocka GE, Dimo T, Nyasse, B, Kimbu SF. Evaluation of the anti-ulcer and toxicity profile of Aloe buettneri in laboratory animals. Afr J Trad Complement Altern Med 2006; 3: 8-20.
29. Kamath P, Subrahmanyam VM, Rao JV, Raj PV. Optimization of cultural conditions for protease production by a fungal species. Indian J Pharm Sci 2010; 72:161-166.
30. Khan MMR, Rahman MM, Islam MS, Begum SA. A simple UV-Spectrophotometric method for the determination of vitamin C content in various fruits and vegetables at Sylhet area in Bangladesh. J Biol Sci 2006; 6: 388-392. 
31. Zhang S, Wu P, Liu J, Du, Y, Yang Z. Roflumilast attenuates doxorubicin-induced cardiotoxicity by targeting inflammation and cellular senescence in cardiomyocytes mediated by SIRT1. Drug Design Develop Ther 2021; 11: 87-97. 
32. Tacey A, Millar S, Qaradakhi T, Smith C, Hayes A, Anderson S, et al. Undercarboxylated osteocalcin has no adverse effect on endothelial function in rabbit aorta or human vascular cells. J Cell Physiol 2021; 236: 2840-2849. 
33. Mohamed ME, Abduldaium MS, Younis NS. Cardioprotective effect of linalool against isoproterenol-induced myocardial infarction. Life (Basel) 2021; 11: 120-136. 
34. Sethi P, Peiris CD. A Review of catecholamine associated cardiomyopathies and channelopathies. Cureus 2020; 12: e6957-e6962.
35. Beshel JA, Beshel FN, Nwangwa JN, Okon IA, Ejim CA, Owu DU. Cardioprotective role of Theobroma cacao against isoproterenol-induced acute myocardial injury. Cardiovasc Hematol Agents Med Chem 2022; 20: 75-80. 
36. Salma AE, Sally AE, Azza H, Heba MIA. Cardioprotective effect of thymol against adrenaline-induced myocardial injury in rats. Heliyon 2020; 6:e0443-e0450. 
37. Giannitsis E, Müller-Bardorff M, Kurowski V, Weidtmann B, Wiegand U, Kampmann M, et al. Independent prognostic value of cardiac troponin T in patients with confirmed pulmonary embolism. Circulation 2000; 102: 211-217. 
38. Moradi-Arzeloo M, Farshid AA, Tamaddonfard E, Asri-Rezaei S. Effects of histidine and vitamin C on isoproterenol-induced acute myocardial infarction in rats. Vet Res Forum 2016; 7:47-54. 
39. Abdulkhaleq FM, Alhussainy TM, Badr MM, Khalil AAA, Gammoh O, Ghanim BY, et al. Anti-oxidative stress effects of vitamins C, E, and B12, and their combination can protect the liver against acetaminophen-induced hepatotoxicity in rats. Drug Design Develop Ther 2018; 12: 3525-3533. 
40. Traber MG, Stevens JF. Vitamins C and E: Beneficial effects from a mechanistic perspective. Free Radic Biol Med 2011;51: 1000-1013. 
41. Riemersma RA, Carruthers KF, Elton RA, Fox KAA. Vitamin C and the risk of acute myocardial infarction. Am J Clin Nutr 2000; 71:1181-1186. 
42. Bagatini MD, Martins CC, Battisti V, Gasparetto D, Da Rosa CS, Spanevello RM, et al. Oxidative stress versus anti-oxidant defenses in patients with acute myocardial infarction. Heart Vessels 2011; 26:55-63. 
43. Davis JL, Paris HL, Beals JW, Binns SE, Giordano GR, Scalzo RL, et al. Liposomal-encapsulated ascorbic acid: Influence on vitamin C bioavailability and capacity to protect against ischemia-reperfusion injury. Nutr Metab Insights 2016; 9: 25-30. 
44. Fomenko I, Sklyarov A, Bondarchuk T, Biletska L, Panasyuk N, Wallace JL. Effects of conventional and hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs in rats with stress-induced and epinephrine-induced gastric damage. Stress 2014; 17: 528-537.
45. Mishra S, Chattopadhyay A, Naaz S, Banerjee A, Ghosh AK, Pal PK, et al. Oleic acid as a restorative agent in alleviating adrenaline induced altered morphofunctional milieu of gastric tissue and mitochondria. Heliyon 2021; 7: e06476-e06493. 
46. Zdravkovic V, Pantovic S, Rosic G, Tomic-Lucic A, Zdravkovic N, Colic M, et al. Histamine blood concentration in ischemic heart disease patients. J Biomed Biotechnol 2011; 2011: 315709-315716. 
47. Owu DU, Obembe AO, Nwokocha CR, Edoho IE, Osim EE. (2012). Gastric ulceration in diabetes mellitus: protective role of vitamin C. ISRN Gastroenterol 2012; 2012:362805-362812.
48. Wang XY, Yin JY, Zhao MM, Liu SY, Nie SP, Xie MY. Gastroprotective activity of polysaccharide from Hericium erinaceus against ethanol-induced gastric mucosal lesion and pylorus ligation-induced gastric ulcer, and its anti-oxidant activities. Carbohydr Polym 2018; 186: 100-109. 
49. Toh JW, Wilson RB. Pathways of gastric carcinogenesis, Helicobacter pylori virulence and interactions with anti-oxidant systems, vitamin C and phytochemicals. Int J Mol Sci 2020; 21: 6451-6496. 
50. Allen A, Flemström G. Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin. Am J Physiol Cell Physiol 2005; 288: C1-C19.
51. Yao X, Forte JG. Cell biology of acid secretion by the parietal cell. Annual Rev Physiol 2003; 65: 103-131. 
52. Arab HH, Salama SA, Omar HA, Arafa ESA, Maghrabi IA. Diosmin protects against ethanol-induced gastric injury in rats: Novel anti-ulcer actions. PloS One 2015; 10: e0122417-e0122437. 
53. Thomas D, Govindhan S, Baiju EC, Padmavathi G, Kunnumakkara AB, Padikkala J. Cyperus rotundus L. prevents non-steroidal anti-inflammatory drug-induced gastric mucosal damage by inhibiting oxidative stress. J Basic Clin Physiol Pharmacol 2015; 26: 485-490. 
54. Obembe AO, Ofutet EO, Okpo-Ene AI, Udondian ES. Gastroprotective role of the combined effects of vitamins C and E following chronic exposure to thermoxidized palm oil in albino rats. J Applied Pharm Sci 2015; 5: 076-080. 
55. Abu Rahma HHA, Attia AAA, Hammam WNED. Study of the role of the anti-oxidants, silymarin and vitamin C in treatment of the indomethacin-induced gastric ulcer in rats. Egyptian Acad J Biol Sci F Toxicol Pest Control 2017; 9: 115-136. 
56. Adefisayo MA, Adeyemi WJ, Alabi QK. Combined but not single administration of vitamin C and l-carnitine ameliorates cisplatin-induced gastric mucosa damage in male rats. Can J Physiol Pharmacol 2018; 96: 830-838.
57. Akolkar G, da Silva Dias D, Ayyappan P, Bagchi AK, Jassal DS, Salemi VMC, et al. Vitamin C mitigates oxidative/nitrosative stress and inflammation in doxorubicin-induced cardiomyopathy. Am J Physiol Heart Circ Physiol 2017; 313: H795- H809. 
58. Swamy AHMV, Uwagikar U, Koti BC, Ahm T, Ronad P, Manjula DV. (2011). Cardioprotective effect of ascorbic acid on doxorubicin-induced myocardial toxicity in rats. Indian J Pharmacol 2011; 43: 507-511.
59. Zuurbier CJ, Bertrand L, Beauloye CR, Andreadou I, Ruiz‐Meana M, Jespersen NR, et al. Cardiac metabolism as a driver and therapeutic target of myocardial infarction. J Cell Mol Med 2020; 24: 5937-5954. 
60. Bashandy SA, Ebaid H, Abdelmottaleb Moussa SA, Alhazza IM, Hassan I, Alaamer A, et al. Potential effects of the combination of nicotinamide, vitamin B2 and vitamin C on oxidative-mediated hepatotoxicity induced by thioacetamide. Lipids Health Dis 2018; 17: 1-9.