Abstract
Acute pancreatitis (AP) is an acute inflammatory condition that results from the digestion of pancreatic tissue by its own enzymes released from the acinar cells. The objective of this study was to investigate the effects of resveratrol on oxidative damage, pro-inflammatory cytokines, and tissue injury involved with AP induced in a rat model using sodium taurocholate (n = 60). There were three treatment groups with 20 rats per group. Groups I and II received 3 % sodium taurocholate solution, while group III underwent the same surgical procedure yet did not receive sodium taurocholate. In addition, group II received 30 mg/kg resveratrol solution. Rats were sacrificed at 2, 6, 12, and 24 h time points following the induction of AP. Blood and pancreatic tissue samples were collected and subjected to biochemical assays, Western blot assays, and histopathologic evaluations. Resveratrol did not reduce trypsin levels and prevent tissue damage. Resveratrol prevented IκB degradation (except for 6 h) and decreased nuclear factor-κB (NF-κB), activator protein-1 (AP-1) (except for 24 h), and levels of TNF-α, IL-6 (except for 24 h), and iNOS in the pancreatic tissue at all time points (P < 0.05). Serum nitric oxide (NO) levels were reduced as well (P < 0.05). Thus, we concluded that resveratrol did not reduce trypsin levels and did not prevent tissue injury despite the reduction in oxidative damage and pro-inflammatory cytokine levels detected in this model of AP.
Similar content being viewed by others
References
Ang AD, Adhikari S, Ng SW, Bhatia M (2009) Expression of nitric oxide synthase isoforms and nitric oxide production in acute pancreatitis and associated lung injury. Pancreatology 9:150–159
Banks PA (1997) Practice guidelines in acute pancreatitis. Am J Gastroenterol 92:377–386
Bhatia M, Brady M, Shokuhi S, Christmas S, Neoptolemos JP, Slavin J (2000) Inflammatory mediators in acute pancreatitis. J Pathol 190:117–125
Bhatia M, Wong FL, Cao Y, Lau HY, Huang J, Puneet P, Chevali L (2005) Pathophysiology of acute pancreatitis. Pancreatology 5:132–144
Bosscha K, Hulstaert PF, Hennipman A, Visser MR, Gooszen HG, Van Vroonhoven TJMV, V d Werken C (1998) Fulminant acute pancreatitis and infected necrosis of open management of the abdomen and “planned” reoperations. J Am Coll Surg 187:255–262
Chen CC, Wang SS, Lee FY, Chang FY, Lee SD (1999) Proinflammatory cytokines in early assessment of the prognosis of acute pancreatitis. Am J Gastroenterol 94:213–218
Cheong H, Ryu SY, Kim KM (1999) Anti-allergic action of resveratrol and related hydroxystilbenes. Planta Med 65:266–268
Cuzzocrea S, Mazzon E, Dugo L, Centorrino T, Ciccolo A, McDonald MC, De Sarro A, Caputi AP, Thiemermann C (2002) Absence of endogenous interlekin-6 enhances the inflammatory response during acute pancreatitis induced by cerulean in mice. Cytokine 18:274–285
Cuzzocrea S, Mazzon E, Dugo L, Serraino I, Centorrino T, Ciccolo A, Van de Loo FAJ, Britti D, Caputi AP, Thiemermann C (2002) Inducible nitric oxide synthase-deficient mice exhibit resistance to the acute pancreatitis induced by cerulein. Shock 17:416–422
Czakό L, Hegyi P, Takács T, Gόg C, Farkas A, Mándy Y, Sz VI, Tiszlavicz L, Lonovics J (2004) Effects of octreotide on acute necrotizing pancreatitis in rabbits. World J Gastroenterol 10:2082–2086
Denham W, Fink G, Yang J, Ulrich P, Tracey K, Norman J (1997) Small molecule inhibition of tumor necrosis factor gene processing during acute pancreatitis prevents cytokine cascade progression and attenuates pancreatitis severity. Am Surg 63:1045–1049
DiMagno MJ, Williams JA, Hao Y, Ernst SA, Owyang C (2004) Endothelial nitric oxide synthase is protective in the initiation of caerulein-induced acute pancreatitis in mice. Am J Physiol Gastrointest Liver Physiol 287:80–87
Eastwood GL (1994) Acute pancreatitis. In: Manual of Gastroenterology, 2nd edn. Little, Brown, Boston, pp. 295–318
Frémont L (2000) Biological effects of resveratrol. Life Scien 66:663–673
Gukovsky I, Retes CN, Vaquero EC, Gukovskaya AS, Pandol SJ (2003) Curcumin ameliorates ethanol and nonethanol experimental pancreatitis. Am J Physiol Gastrointest Liver Physiol 284:G85–G95
Gülçubuk A, Sonmez K, Gurel A, Altunatmaz K, Gurler N, Aydin S, Oksuz L, Uzun H, Guzel O (2005) Pathologic alterations detected in acute pancreatitis induced by sodium taurocholate in rats and therapeutic effects of curcumin, ciprofloxacin and metronidazole combination. Pancreatology 5:345–353
Hietaranta AJ, Saluja AK, Bhagat L, Singh VP, Song AM, Steer ML (2001) Relationship between NF-κB and trypsinogen activation in rat pancreas after supramaximal caerulein stimulation. Biochem Bioph Res Co 280:388–395
Hung LM, Chen JK, Huang SS, Lee RS, Su MJ (2000) Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovasc Res 47:549–555
Jang DS, Kang BS, Ryu SY, Chang IM, Min KR, Kim Y (1999) Inhibitory effects of resveratrol analogs on unopsonized zymosan-induced oxygen radical production. Biochem Pharmacol 57:705–712
Jha RK, Ma Q, Sha H (2008) The protective effect of resveratrol on the intestinal mucosal barrier in rats with severe acute pancreatitis. Med Sci Monit 14:14–19
Lawiński M, Śledziński Z, Juraniec JK, Spodnik JH, Woźniak M, Boguslawski W (2005) Does resveratrol prevent free radical-induced acute pancreatitis? Pancreas 31:43–47
Leonard SS, Xia C, Jiang BH, Stinefelt B, Klandorf H, Harris GK, Shi X (2003) Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem Biophys Res Commun 309:1017–1026
Li ZD, Ma QY, Wang CA (2006) Effect of resveratrol on pancreatic oxygen free radicals in rats with severe acute pancreatitis. World J Gastroenterol 7:137–140
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Ma ZH, Ma QY (2005) Resveratrol: a medical drug for acute pancreatitis. World J Gastroenterol 11:3171–3174
Ma ZH, Ma QY, Wang LC, Sha HC, Wu SL, Zhang M (2005) Effect of resveratrol on peritoneal macrophages in rats with severe acute pancreatitis. Inflamm Res 54:522–527
Manna SK, Mukhopadhyay A, Aggarwal BB (2000) Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-κB, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J Immunol 164:6509–6519
McNary MH, Baldwin AS (2000) Chemopreventive properties of trans-Resveratrol are associated with inhibition of activation of the IκB kinase. Cancer Res 60:3477–3483
Meng Y, Ma QY, Kou XP, Xu J (2005) Effect of resveratrol on activation of nuclear factor kappa-B and inflammatory factors in rat model of acute pancreatitis. World J Gastroenterol 11:525–528
Mettu SR, Wig JD, Khullar M, Singh G, Gupta R (2003) Efficacy of serum nitric oxide level estimation in assessing the severity of necrotizing pancreatitis. Pancreatology 3:506–514
Mews P, Phillips P, Fahmy R, Korsten M, Pirola R, Wilson A, Apte M (2002) Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis. Gut 50:535–541
Osman MO, Gesser B, Mortensen JT, Matsushima K, Jensen SL, Larsen CG (2002) Profiles or pro-inflammatory cytokines in the serum of rabbits after experimentally induced acute pancreatitis. Cytokine 17:53–59
Pellegatta F, Bertelli AAE, Staels B, Duhem C, Fulgenzi A, Ferrero E (2003) Different short-and long-term effects of resveratrol on nuclear factor-κB phosphorylation and nuclear appearance in human endothelial cells. Am J Clin Nutr 77:1220–1228
Sha H, Ma Q, Jha RK, Wang Z (2009) Resveratrol ameliorates lung injury via inhibition of apoptosis in rats with severe acute pancreatitis. Exp Lung Res 35:344–358
Sha H, Ma Q, Jha RK, Xu F, Wang L, Wang Z, Zhao Y, Fan F (2008) Resveratrol ameliorates hepatic injury via the mitochondrial pathway in rats with severe acute pancreatitis. European J Pharmacol 601:136–142
Szabolcs A, Varga IS, Varga C, Berko A, Kaszaki J, Letoha T, Tiszlavicz T, Sári R, Lonovics J, Takács T (2006) Beneficial effect of resveratrol on cholecystokinin-induced experimental pancreatitis. European J Pharmacol 532:187–193
Tsai SH, Lin-Shiau SY, Lin JK (1999) Suppression of nitric oxide synthase and the down-regulation of the activation of NF-κB in macrophages by resveratrol. Br J Pharmacol 126:673–680
Uhl W, Warshaw A, Imrie C, Bassi C, McKay CJ, Lankisch PG, Carter R, Magno ED, Banks PA, Whitcomb DC, Dervenis C, Ulrich CD, Satake K, Ghaneh P, Hartwig W, Werner J, McEntee G, Neoptolemos JP, Büchler MW (2002) IAP Guidelines fort he surgical management of acute pancreatitis. Pancreatology 2:565–573
Wallerath T, Deckert G, Ternes T, Anderson H, Li H, Witte K, Förstermann U (2002) Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 106:1652–1658
Wang L, Ma Q, Chen X, Sha H, Ma Z (2008) Effects of resveratrol on calcium regulation in rats with severe acute pancreatitis. Eur J Pharmacol 580:271–276
Acknowledgement
This study was supported by the Research Fund of Istanbul University (project number 2700/30042008).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gulcubuk, A., Haktanir, D., Cakiris, A. et al. The effects of resveratrol on tissue injury, oxidative damage, and pro-inflammatory cytokines in an experimental model of acute pancreatitis. J Physiol Biochem 70, 397–406 (2014). https://doi.org/10.1007/s13105-014-0317-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13105-014-0317-4