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Protective effects of resveratrol on hepatic ischemia reperfusion injury in streptozotocin-induced diabetic rats

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Abstract

Resveratrol (RSV) is a natural polyphenolic compound having antioxidant effects. This study was designed to investigate the protective effects of resveratrol against oxidative stress in hepatic ischemia–reperfusion (I/R) injury in streptozotocin (STZ)-induced diabetic rats. STZ was injected intraperitonally (i.p.) to 18 Sprague–Dawley albino rats, which were divided into three groups, each having six rats. First group was non-treated diabetic group (D), second diabetic group was subjected to 30 min of hepatic ischemia followed by a 45-min reperfusion period (D + I/R), and third diabetic group was subjected to 30 min of hepatic ischemia followed by a 45-min reperfusion period and treated with 20 mg/kg/day oral RSV before 30 min I/R injury (D + I/R + RSV). At the end of the experimental period, animals were decapitated, and blood samples were collected to determine tissue tumor necrosis factor-α (TNF-α) levels. Liver and lung tissue samples were obtained for the evaluation of biochemical parameters including malondialdehyde (MDA) and glutathione (GSH) levels and histopathological examinations. Compared to control, I/R injury resulted in decreases in GSH levels and increases in MDA levels. Tissue TNF-α levels were also increased in the D + I/R group compared to D group. Treatment with RSV prevented the alterations on biochemical parameters and histopathological changes induced by I/R. We demonstrate that in diabetic rats, hepatic I/R injury is associated with an augmented inflammatory response and oxidative stress, while RSV pre-treatment significantly decreased these responses. Larger clinical studies are desirable to determine the exact role(s) of RSV on hepatic I/R injury among diabetic subjects.

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References

  1. American Diabetes Association (2013) Diagnosis and classification of diabetes mellitus. Diabetes Care 36(Suppl 1):S67–S74

    Article  Google Scholar 

  2. Yazgan ÜC, Taşdemir E, Bilgin HM, Deniz Obay B, Şermet A, Elbey B (2015) Comparison of the anti-diabetic effects of resveratrol, gliclazide and losartan in streptozotocin-induced experimental diabetes. Arch Physiol Biochem 121:157–161

    Article  CAS  PubMed  Google Scholar 

  3. Rochette L, Zeller M, Cottin Y, Vergely C (2014) Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta 1840:2709–2729

    Article  CAS  PubMed  Google Scholar 

  4. Schmatz R, Perreira LB, Stefanello N et al (2012) Effects of resveratrol on biomarkers of oxidative stress and on the activity of delta aminolevulinic acid dehydratase in liver and kidney of streptozotocin-induced diabetic rats. Biochimie 94:374–383

    Article  CAS  PubMed  Google Scholar 

  5. Pektaş MB, Sadi G, Koca HB et al (2016) Resveratrol ameliorates the components of hepatic inflammation and apoptosis in a rat model of streptozotocin-induced diabetes. Drug Dev Res 77:12–19

    Article  CAS  PubMed  Google Scholar 

  6. Prabhakar O (2013) Cerebroprotective effect of resveratrol through antioxidant and anti-inflammatory effects in diabetic rats. Naunyn Schmiedebergs Arch Pharmacol 386:705–710

    Article  CAS  PubMed  Google Scholar 

  7. Moridi H, Karimi J, Sheikh N et al (2015) Resveratrol-dependent down-regulation of receptor for advanced glycation end-products and oxidative stress in kidney of rats with diabetes. Int J Endocrinol Metab 20(13):e23542

    Google Scholar 

  8. Gedik E, Girgin S, Ozturk H, Obay BD, Ozturk H, Buyukbayram H (2008) Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats. World J Gastroenterol 14:7101–7106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dünschede F, Erbes K, Kircher A et al (2006) Reduction of ischemia reperfusion injury after liver resection and hepatic inflow occlusion by alpha-lipoic acid in humans. World J Gastroenterol 12:6812–6817

    Article  PubMed  PubMed Central  Google Scholar 

  10. Liu B, Qian JM (2015) Cytoprotective role of heme oxygenase-1 in liver ischemia reperfusion injury. Int J Clin Exp Med 8:19867–19873

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Yonamine CY, Pinheiro-Machado E, Michalani ML et al (2016) Resveratrol improves glycemic control in insulin treated diabetic rats: participation of thehepatic territory. Nutr Metab (Lond) 13:44. https://doi.org/10.1186/s12986-016-0103-0

    Article  CAS  Google Scholar 

  12. Malhotra A, Bath S, Elbarbry F (2015) An organ system approach to explore the antioxidative, anti-inflammatory, and cytoprotective actions of resveratrol. Oxid Med Cell Longev 2015:803971. https://doi.org/10.1155/2015/803971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Oya S, Nur A, Gül G (2008) Resveratrol and cardiovascular system. Turk J Biochem 33:117–121

    Google Scholar 

  14. Beuge JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–311

    Article  Google Scholar 

  15. Beutler E (1975) Glutathione in red blood cell metabolism. A manual of biochemical methods. Grune and Stratton, New York, pp 112–114

    Google Scholar 

  16. Qin Y, Li Z, Wang Z et al (2014) Ghrelin contributes to protection of hepatocellular injury induced by ischaemia/reperfusion. Liver Int 34:567–575

    Article  CAS  PubMed  Google Scholar 

  17. Rossetti A, Togliatto G, Rolo AP et al (2017) Unacylated ghrelin prevents mitochondrial dysfunction in a model of ischemia/reperfusion liverinjury. Cell Death Discov 3:17077. https://doi.org/10.1038/cddiscovery.2017.77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Liu Z, Zhang X, Xiao Q et al (2017) Pretreatment donors after circulatory death with simvastatin alleviates liver ischemia reperfusion injury through a KLF2-dependent mechanism in rat. Oxid Med Cell Longev 2017:3861914. https://doi.org/10.1155/2017/3861914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Chang C, Zhao Y, Song G, She K (2018) Resveratrol protects hippocampal neurons against cerebral ischemia-reperfusion injury via modulating JAK/ERK/STAT signaling pathway in rats. J Neuroimmunol 315:9–14

    Article  CAS  PubMed  Google Scholar 

  20. Erkasap S, Erkasap N, Bradford B (2017) The effect of leptin and resveratrol on JAK/STAT pathways and Sirt-1 gene expression in the renal tissue of ischemia/reperfusion induced rats. Bratisl Lek Listy 118:443–448

    CAS  PubMed  Google Scholar 

  21. Seong H, Ryu J, Yoo WS et al (2017) Resveratrol ameliorates retinal ischemia/reperfusion injury in C57BL/6 J mice via downregulation of caspase-3. Curr Eye Res 42:1650–1658

    Article  CAS  PubMed  Google Scholar 

  22. Yildiz F, Terzi A, Coban S et al (2009) Protective effects of resveratrol on small intestines against intestinal ischemia-reperfusion injury in rats. J Gastroenterol Hepatol 24:1781–1785

    Article  CAS  PubMed  Google Scholar 

  23. Shimizu K, Miyagi S, Miyazawa K et al (2016) Resveratrol prevents warm ischemia-reperfusion injury in liver grafts from non-heart-beating donor rats. Transplant Proc 48:1221–1225

    Article  CAS  PubMed  Google Scholar 

  24. He D, Guo Z, Pu JL et al (2016) Resveratrol preconditioning protects hepatocytes against hepatic ischemia reperfusion injury via Toll-like receptor 4/nuclear factor-κ B signaling pathway in vitro and in vivo. Int Immunopharmacol 35:201–209

    Article  CAS  PubMed  Google Scholar 

  25. Sehirli O, Sener E, Cetinel S, Yuksel M, Gedik N, Sener G (2008) α-Lipoic acid protects against renal ischaemia-reperfusion injury in rats. Clin Exp Pharmacol Physiol 35:249–255

    Article  CAS  PubMed  Google Scholar 

  26. Bradamante S, Barenghi L, Villa A (2004) Cardiovascular protective effects of resveratrol. Cardiovasc Drug Rev 22:169–188

    Article  CAS  PubMed  Google Scholar 

  27. Leonard SS, Xia C, Jiang BH et al (2003) Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem Biophys Res Commun 309:1017–1026

    Article  CAS  PubMed  Google Scholar 

  28. Chi KK, Zhang WH, Chen Z et al (2016) Comparison of quercetin and resveratrol in the prevention of injury due to testicular torsion/detorsion in rats. Asian J Androl 18:908–912

    CAS  PubMed  Google Scholar 

  29. Cheng L, Jin Z, Zhao R, Ren K, Deng C, Yu S (2015) Resveratrol attenuates inflammation and oxidative stress induced by myocardial ischemia-reperfusion injury: role of Nrf2/ARE pathway. Int J Clin Exp Med 8:10420–10428

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Kirimlioglu H, Ecevit A, Yilmaz S, Kirimlioglu V, Karabulut AB (2008) Effect of resveratrol and melatonin on oxidative stress enzymes, regeneration, and hepatocyte ultrastructure in rats subjected to 70% partial hepatectomy. Transplant Proc 40:285–289

    Article  CAS  PubMed  Google Scholar 

  31. Kato M, Sawada T, Kita J, Shimoda M, Kubota K (2010) Erythropoietin ameliorates early ischemia-reperfusion injury following the Pringle maneuver. World J Gastroenterol 16:4838–4845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Tao X, Sun X, Xu L (2016) Total flavonoids from rosa laevigata michx fruit ameliorates hepatic ischemia/reperfusion injury through inhibition of oxidative stress and inflammation in rats. Nutrients 8:418. https://doi.org/10.3390/nu8070418

    Article  CAS  PubMed Central  Google Scholar 

  33. Fang L, Gao H, Zhang W, Zhang W, Wang Y (2015) Resveratrol alleviates nerve injury after cerebral ischemia and reperfusion in mice by inhibiting inflammation and apoptosis. Int J Clin Exp Med 8:3219–3226

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Thirunavukkarasu M, Penumathsa SV, Koneru S (2007) Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes: role of nitric oxide, thioredoxin, and heme oxygenase. Free Radic Biol Med 43:720–729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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This study was not funded from any source, except the primary institutional support.

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Correspondence to Hanife Serife Aktaş or Sarfraz Ahmad.

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All procedures performed in this study involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Aktaş, H.S., Ozel, Y., Ahmad, S. et al. Protective effects of resveratrol on hepatic ischemia reperfusion injury in streptozotocin-induced diabetic rats. Mol Cell Biochem 460, 217–224 (2019). https://doi.org/10.1007/s11010-019-03582-z

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