Gallic acid protects the liver in rats against injuries induced by transient ischemia-reperfusion through regulating microRNAs expressions

Document Type: Original Article

Authors

1 Yasuj University of Medical Sciences, Yasuj, Iran

2 Alimentary Tract Research Center, Physiology Research Center, Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

3 Department of Pathobiology, School of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

Abstract

Objective(s): Gallic acid (GA) is a highly effective antioxidant, which its beneficial effects are well known, but its impact on expression of microRNAs (miRs) following hepatic ischemia-reperfusion (I/R) is not well recognized. Therefore, the current research was designed to specify the beneficial effect of GA on miRs (122 and 34a), liver functional tests, and histopathological alterations beyond I/R-induced hepatic injury.
Materials and Methods: Thirty-two rats were randomly divided into four groups (8 per group) including: sham-operated (S), I/R, and GA+I/R pretreated groups. Rats in sham-operated group received physiologic saline (N/S, 2 ml/kg), on a weekly basis, once a day via intraperitoneally route), then a midline abdominal surgery was performed. IR, and GA+IR pretreated groups received physiologic saline (2 ml/kg), and GA (50, and 100 mg per kg) for same time, IP, respectively, before induction of transient ischemia. One hour after reperfusion, biochemical, and histopathological evaluations were performed and expression of miRs were evaluated.
Results: The results showed that GA reduced the concentrations of liver enzymes, miR-122, and miR-34a in serum, and preserved liver cells changes induced by I/R injury.
Conclusion: These findings showed that GA has beneficial effect on liver damage induced by I/R. Therefore, it is suggested that GA can be administered as an anti-miR before elective hepatic surgeries for prevention of this complication.

Keywords

Main Subjects


1. Abd-Elbaset M, Arafa E-SA, El Sherbiny GA, Abdel-Bakky MS, Elgendy ANA. Quercetin modulates iNOS, eNOS and NOSTRIN expressions and attenuates oxidative stress in warm hepatic ischemia-reperfusion injury in rats. BJBAS 2015; 4:246-255.
2. Collard CD, Gelman S. Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology 2001; 94:1133-1138.
3. Topliss J, Clark A, Ernst E, Hufford C, Johnston G, Rimoldi J, et al. Natural and synthetic substances related to human health (IUPAC Technical Report). IUPAC 2002; 74:1957-1985.
4. Zhang HY, Wang LF. Theoretical elucidation on structure–antioxidant activity relationships for indolinonic hydroxylamines. Bioorg Med Chem Lett 2002;12:225-227.
5. Prince PSM, Priscilla H, Devika PT. Gallic acid prevents lysosomal damage in isoproterenol induced cardiotoxicity in Wistar rats. Eur J Pharmacol 2009; 615:139-143.
6. Padma VV, Sowmya P, Felix TA, Baskaran R, Poornima P. Protective effect of gallic acid against lindane induced toxicity in experimental rats. Food Chem Toxicol 2011; 49:991-998.
7. Verma S, Singh A, Mishra A. Gallic acid: molecular rival of cancer. Environ Toxicol Pharmacol 2013; 35:473-485.
8. Soong YY, Barlow PJ. Quantification of gallic acid and ellagic acid from longan (Dimocarpus longan Lour.) seed and mango (Mangifera indica L.) kernel and their effects on antioxidant activity. Food Chem 2006; 97:524-530.
9. Kim SH, Jun CD, Suk K, Choi BJ, Lim H, Park S, et al. Gallic acid inhibits histamine release and pro-inflammatory cytokine production in mast cells. Toxicol Sci 2005; 91:123-131.
10. Chanwitheesuk A, Teerawutgulrag A, Kilburn JD, Rakariyatham N. Antimicrobial gallic acid from Caesalpinia mimosoides Lamk. Food Chem 2007; 100:1044-1048.
11. Wang K, Zhu X, Zhang K, Zhu L, Zhou F. Investigation of gallic acid induced anticancer effect in human breast carcinoma MCF‐7 cells. J Biochem Mol Toxicol 2014; 28:387-393.
12. Sen S, Asokkumar K, Umamaheswari M, Sivashanmugam A, Subhadradevi V. Antiulcerogenic effect of gallic acid in rats and its effect on oxidant and antioxidant parameters in stomach tissue. Indian J Pharm Sci 2013; 75:149-155.
13. Mansouri MT, Farbood Y, Sameri MJ, Sarkaki A, Naghizadeh B, Rafeirad M. Neuroprotective effects of oral gallic acid against oxidative stress induced by 6-hydroxydopamine in rats. Food Chem 2013; 138:1028-1033.
14. Badavi M, Sadeghi N, Dianat M, Samarbafzadeh A. Effects of gallic Acid and cyclosporine a on antioxidant capacity and cardiac markers of rat isolated heart after ischemia/reperfusion. Iran Red Crescent Med J 2014; 16:16424-16431.
15. Dianat M, Sadeghi N, Badavi M, Panahi M, Taheri Moghadam M. Protective effects of co-administration of gallic Acid and cyclosporine on rat myocardial morphology against ischemia/reperfusion. Jundishapur J Nat Pharm Prod 2014; 9:17186-17192.
16. Rahman K. Studies on free radicals, antioxidants, and co-factors. Clin Interv Aging 2007; 2:219-236.
17. Thulasingam S, Massilamany C, Gangaplara A, Dai H, Yarbaeva S, Subramaniam S, et al. miR-27b*, an oxidative stress-responsive microRNA modulates nuclear factor-kB pathway in RAW 264.7 cells. Mol Cell Biochem 2011; 352:181-188.
18. He J, Jiang BH. Interplay between reactive oxygen species and microRNAs in cancer. Curr Pharmacol Rep 2016; 2:82-90.
19. Chang J, Nicolas E, Marks D, Sander C, Lerro A, Buendia MA, et al. miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and maydownregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol 2004; 1:106-113.
20. Castoldi M, Spasic MV, Altamura S, Elmén J, Lindow M, Kiss J, et al. The liver-specific microRNA miR-122 controls systemic iron homeostasis in mice. J Clin Invest 2011; 121:1386-1396.
21. Cermelli S, Ruggieri A, Marrero JA, Ioannou GN, Beretta L. Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease. PLoS One 2011;6:23937-23945.
22. Afonso MB, Rodrigues PM, Simão AL, Castro RE. Circulating microRNAs as potential biomarkers in non-alcoholic fatty liver disease and hepatocellular carcinoma. J Clin Med 2016; 5:30-50.
23. Rasool MK, Sabina EP, Ramya SR, Preety P, Patel S, Mandal N, et al. Hepatoprotective and antioxidant effects of gallic acid in paracetamol-induced liver damage in mice. J Pharm Pharmacol 2010; 62:638-643.
24. Wang J, Tang L, White J, Fang J. Inhibitory effect of gallic acid on CCl4-mediated liver fibrosis in mice. Cell Biochem Biophys 2014; 69:21-26.
25. Bayramoglu G, Kurt H, Bayramoglu A, Gunes HV, Degirmenci İ, Colak S. Preventive role of gallic acid on hepatic ischemia and reperfusion injury in rats. Cytotechnology 2015; 67:845-849.
26. Arda-Pirincci P, Bolkent S, Yanardag R. The role of zinc sulfate and metallothionein in protection against ethanol-induced gastric damage in rats. Dig Dis Sci 2006; 51:2353-2360.
27. Mard SA, Akbari G, Mansouri E, Parsanahad M. Renoprotective effect of crocin following liver ischemia/reperfusion injury in Wistar rats. Iran J Basic Med Sci 2017; 20:1172-1177.
28. Kim HJ, Joe Y, Yu JK, Chen Y, Jeong SO, Mani N, et al. Carbon monoxide protects against hepatic ischemia/reperfusion injury by modulating the miR-34a/SIRT1 pathway. Biochim Biophys Acta 2015; 1852:1550-1559.
29. Akbari G, Mard SA, Dianat M, Mansouri E. The hepatoprotective and microRNAs downregulatory effects of crocin following hepatic ischemia-reperfusion injury in rats. Oxid Med Cell Longev 2017; 2017:1702967-1702978.
30. Shifeng H, Danni W, Pu C, Ping Y, Ju C, Liping Z. Circulating liver-specific miR-122 as a novel potential biomarker for diagnosis of cholestatic liver injury. PLoS One 2013; 8:73133-73140.
31. Farid WR, Pan Q, van der Meer AJ, de Ruiter PE, Ramakrishnaiah V, de Jonge J, et al. Hepatocyte‐derived microRNAs as serum biomarkers of hepatic injury and rejection after liver transplantation. Liver Transpl 2012; 18:290-297.
32. Bader AG. miR-34–a microRNA replacement therapy is headed to the clinic. Front Genet 2012; 3:120-129.
33. Bernardo BC, Gao XM, Winbanks CE, Boey EJ, Tham YK, Kiriazis H, et al. Therapeutic inhibition of the miR-34 family attenuates pathological cardiac remodeling and improves heart function. Proc Nat Acad Sci U S A 2012; 109:17615-17620.
34. Xu Y, Zalzala M, Xu J, Li Y, Yin L, Zhang Y. A metabolic stress-inducible miR-34a-HNF4alpha pathway regulates lipid and lipoprotein metabolism. Nat Commun 2015; 6:7466-7486.
35. Li N, Muthusamy S, Liang R, Sarojini H, Wang E. Increased expression of miR-34a and miR-93 in rat liver during aging, and their impact on the expression of Mgst1 and Sirt1. Mech Ageing Dev  2011; 132:75-85.
36. Liu XL, Pan Q, Zhang RN, Shen F, Yan SY, Sun C, et al. Disease-specific miR-34a as diagnostic marker of non-alcoholic steatohepatitis in a Chinese population. World J Gastroenterol 2016; 22:9844-9852.
37. Shan W, Gao L, Zeng W, Hu Y, Wang G, Li M, et al. Activation of the SIRT1/p66shc antiapoptosis pathway via carnosic acid-induced inhibition of miR-34a protects rats against nonalcoholic fatty liver disease. Cell Death Dis 2015; 6:1833-1842.
38. Parikh M, Patel A, Ptel K. Protective effect of Momordica charantia against hepatic ischemic reperfusion injury model in rats. Austin J Pharmacol Ther 2015; 3:1064-1068.
39. Suzuki HI, Yamagata K, Sugimoto K, Iwamoto T, Kato S, Miyazono K. Modulation of microRNA processing by p53. Nature 2009;460:529-533.