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Şiddetli Akut Pantreatitli Ratlarda Tek-Doz Triptolitin İyileşmeye Etkisi

Year 2020, Volume: 22 Issue: 2, 105 - 108, 30.08.2020
https://doi.org/10.18678/dtfd.728067

Abstract

Amaç: Şiddetli akut pankreatit (SAP) yüksek morbidite ve mortalite riski taşır. SAP'nin proenflamatuar yanıt fazı kontrol edilemezse, çoklu organ yetmezliği (ÇOY) ile sonuçlanabilir. Nükleer faktör-kappa B (NF-κB) aktivasyonu ÇOY'un gelişiminde önemli bir rol oynar. Bu çalışmada, bir anti-enflamatuar ve immünsüpresif ajan olan triptolidin SAP'lı sıçanlarda iyileştirici etkilerinin araştırılması amaçlanmıştır.
Gereç ve Yöntemler: Toplam 20 Wistar-Albino sıçanı SAP ve triptolide tedavi (TT) grubu olmak üzere iki gruba ayrıldı. SAP her iki grupta da intraperitoneal cerulein (50 mg/kg) enjeksiyonu ile indüklendi. TT grubuna, SAP indüksiyonundan 24 saat sonra tek bir doz (0.2 mg/kg) triptolid uygulandı. Serum ALT, AST, GGT, Lipaz, Glikoz, ALP ve amilaz düzeyleri ve pankreatik doku örnekleri incelendi.
Bulgular: Serum glukoz ve amilaz düzeyleri TT grubunda anlamlı olarak daha düşük bulundu (sırasıyla p=0.011 ve p=0.035). Diğer biyokimyasal parametreler açısından gruplar arasında anlamlı bir fark yoktu. Pankreas ödemi, asiner hücre dejenerasyonu, yağ nekrozu, intrapankreatik&perivasküler inflamasyon ve peripankreatik yağ dokusunda inflamasyon her iki grupta da sık görülen histopatolojik bulgulardı. Gruplar arasında histopatolojik değişiklikler açısından anlamlı bir fark yoktu.
Sonuç: Cerulein kaynaklı pankreatit, deneysel SAP için başarılı bir yöntemdir. Tek doz triptolid tedavisinin iyileştirici etkileri SAP'nin erken evresinde belirgin değildir. Pankreatik doku histopatolojik ve biyokimyasal parametreler açısından incelendiğinde, triptolidin enflamatuar ve oksidatif stres üzerindeki terapötik etkileri yeterli düzeyde değildi.

References

  • Portelli M, Jones CD. Severe acute pancreatitis: pathogenesis, diagnosis and surgical management. Hepatobiliary Pancreat Dis Int. 2017;16(2):155-9.
  • Zerem E. Treatment of severe acute pancreatitis and its complications. World J Gastrenterol. 2014;20(38):13879-92.
  • Huang H, Liu Y, Daniluk J, Gaiser S, Chu J, Wang H, et al. Activation of nuclear factor-κB in acinar cells increases the severity of pancreatitis in mice. Gastroenterology. 2013;144(1):202-10.
  • Jakkampudi A, Jangala R, Reddy BR, Mitnala S, Nageshwar Reddy D, Talukdar R. NF-κB in acute pancreatitis: Mechanisms and therapeutic potential. Pancreatology. 2016;16(4):477-88.
  • Watanabe T, Kudo M, Strober W; Immunopathogenesis of pancreatitis. Mucosal Immunol. 2017;10(2):283-98.
  • He L, Peng X, Liu G, Tang C, Liu H, Liu F, et al. Anti-inflammatory effects of triptolide on IgA nephropathy in rats. Immunopharmacol Immunotoxicol. 2015;37(5):421-7.
  • Song C, Wang Y, Cui L, Yan F, Shen S. Triptolide attenuates lipopolysaccharide-induced inflammatory responses in human endothelial cells: involvement of NF-κB pathway. BMC Complement Altern Med. 2019;19(1):198.
  • Zhao YF, Zhai WL, Zhang SJ, Chen XP. Protection effect of triptolide to liver injury in rats with severe acute pancreatitis. Hepatobiliary Pancreat Dis Int. 2005;4(4):604-8.
  • Garg PK, Singh VP. Organ failure due to systemic injury in acute pancreatitis. Gastroenterology. 2019;156(7):2008-23.
  • Zhou MT, Chen CS, Chen BC, Zhang QY, Andersson R. Acute lung injury and ARDS in acute pancreatitis: Mechanisms and potential intervention. World J Gastroenterol. 2010;16(17):2094-9.
  • Zhang XP, Wang L, Zhou YF. The pathogenic mechanism of severe acute pancreatitis complicated with renal injury: A review of current knowledge. Dig Dis Sci. 2008;53(2):297-306.
  • Garcia M, Calvo JJ. Cardiocirculatory pathophysiological mechanisms in severe acute pancreatitis. World J Gastrointest Pharmacol Ther. 2010;1(1):9-14.
  • Saluja AK, Steer ML. Pathophysiology of pancreatitis. Role of cytokines and other mediators of inflammation. Digestion. 1999;60(Suppl 1):27-33.
  • Gukovsky I, Gukovskaya AS, Blinman TA, Zaninovic V, Pandol SJ. Early NF-κB activation is associated with hormone-induced pancreatitis. Am J Physiol. 1998;275(6):G1402-14.
  • Chen X, Ji B, Han B, Ernst SA, Simeone D, Logsdon CD. NF-κB activation in the pancreas induces pancreatic and systemic inflammatory response. Gastroenterology. 2002;122(2): 448-57.
  • Rakonczay Z Jr, Hegyi P, Takács T, McCarroll J, Saluja AK. The role of NF-κB activation in the pathogenesis of acute pancreatitis. Gut. 2008;57(2):259-67.
  • Hyun JJ, Lee HS. Experimental models of pancreatitis. Clin Endosc. 2014;47(3):212-6.
  • Lampel M, Kern HF. Acute interstitial pancreatitis in the rat induced by excessive doses of a pancreatic secretagogue. Virchows Arch A Pathol Anat Histol. 1977;373(2):97-117.
  • Saluja A, Saito I, Saluja M, Houlihan MJ, Powers RE, Meldolesi J, et al. In vivo rat pancreatic acinar cell function during supramaximal stimulation with caerulein. Am J Physiol. 1985;249(6 Pt 1):G702-10.
  • Zhao G, Vaszar LT, Qiu D, Shi L, Kao PN. Anti-inflammatory effects of triptolide in human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2000;11;279(5):L958-66.
  • Gray KD, Simovic MO, Chapman WC, Blackwell TS, Christman JW, Washington MK, et al. Systemic nf-kappaB activation in a transgenic mouse model of acute pancreatitis. J Surg Res. 2003;110(1):310-4.

Healing Effects of Single-Dose Triptolide in Rats with Severe Acute Pancreatitis

Year 2020, Volume: 22 Issue: 2, 105 - 108, 30.08.2020
https://doi.org/10.18678/dtfd.728067

Abstract

Aim: Severe acute pancreatitis (SAP) carries high morbidity and mortality risk. If the proinflammatory response phase of SAP cannot be controlled, it may result in multiorgan failure (MOF). Nuclear factor-kappa B (NF-κB) activation plays an important role in the development of MOF. In this study, it was aimed to investigate the healing effects of triptolide, an anti-inflammatory and immunosuppressive agent in rats with SAP.
Material and Methods: A total of 20 Wistar-Albino rats were divided into two groups as the SAP and triptolide treatment (TT) groups. SAP was induced by intraperitoneal injection of cerulean (50 mg/kg) in both groups. TT group was administered a single dose (0.2 mg/kg) triptolide 24 hour after the induction of SAP. Serum ALT, AST, GGT, Lipase, Glucose, ALP and amylase levels and pancreatic tissue samples were examined.
Results: Serum glucose and amylase levels were found to be significantly lower in the TT group (p=0.011 and p=0.035, respectively). There was no significant difference between the groups in terms of other biochemical parameters. Pancreatic edema, acinar cell degeneration, fat necrosis, intrapancreatic&perivascular inflammation, inflammation in the peripancreatic fat tissue were common histopathological findings in both groups. There was no significant difference between the groups in terms of histopathologic changes.
Conclusion: Cerulein-induced pancreatitis is a successful method for experimental SAP. The healing effects of single-dose triptolide treatment are not evident in the early phase of SAP. The therapeutic effects of triptolide on inflammatory and oxidative stress were not significantly approved by histopathological and biochemical parameters by the pancreatic tissue.

References

  • Portelli M, Jones CD. Severe acute pancreatitis: pathogenesis, diagnosis and surgical management. Hepatobiliary Pancreat Dis Int. 2017;16(2):155-9.
  • Zerem E. Treatment of severe acute pancreatitis and its complications. World J Gastrenterol. 2014;20(38):13879-92.
  • Huang H, Liu Y, Daniluk J, Gaiser S, Chu J, Wang H, et al. Activation of nuclear factor-κB in acinar cells increases the severity of pancreatitis in mice. Gastroenterology. 2013;144(1):202-10.
  • Jakkampudi A, Jangala R, Reddy BR, Mitnala S, Nageshwar Reddy D, Talukdar R. NF-κB in acute pancreatitis: Mechanisms and therapeutic potential. Pancreatology. 2016;16(4):477-88.
  • Watanabe T, Kudo M, Strober W; Immunopathogenesis of pancreatitis. Mucosal Immunol. 2017;10(2):283-98.
  • He L, Peng X, Liu G, Tang C, Liu H, Liu F, et al. Anti-inflammatory effects of triptolide on IgA nephropathy in rats. Immunopharmacol Immunotoxicol. 2015;37(5):421-7.
  • Song C, Wang Y, Cui L, Yan F, Shen S. Triptolide attenuates lipopolysaccharide-induced inflammatory responses in human endothelial cells: involvement of NF-κB pathway. BMC Complement Altern Med. 2019;19(1):198.
  • Zhao YF, Zhai WL, Zhang SJ, Chen XP. Protection effect of triptolide to liver injury in rats with severe acute pancreatitis. Hepatobiliary Pancreat Dis Int. 2005;4(4):604-8.
  • Garg PK, Singh VP. Organ failure due to systemic injury in acute pancreatitis. Gastroenterology. 2019;156(7):2008-23.
  • Zhou MT, Chen CS, Chen BC, Zhang QY, Andersson R. Acute lung injury and ARDS in acute pancreatitis: Mechanisms and potential intervention. World J Gastroenterol. 2010;16(17):2094-9.
  • Zhang XP, Wang L, Zhou YF. The pathogenic mechanism of severe acute pancreatitis complicated with renal injury: A review of current knowledge. Dig Dis Sci. 2008;53(2):297-306.
  • Garcia M, Calvo JJ. Cardiocirculatory pathophysiological mechanisms in severe acute pancreatitis. World J Gastrointest Pharmacol Ther. 2010;1(1):9-14.
  • Saluja AK, Steer ML. Pathophysiology of pancreatitis. Role of cytokines and other mediators of inflammation. Digestion. 1999;60(Suppl 1):27-33.
  • Gukovsky I, Gukovskaya AS, Blinman TA, Zaninovic V, Pandol SJ. Early NF-κB activation is associated with hormone-induced pancreatitis. Am J Physiol. 1998;275(6):G1402-14.
  • Chen X, Ji B, Han B, Ernst SA, Simeone D, Logsdon CD. NF-κB activation in the pancreas induces pancreatic and systemic inflammatory response. Gastroenterology. 2002;122(2): 448-57.
  • Rakonczay Z Jr, Hegyi P, Takács T, McCarroll J, Saluja AK. The role of NF-κB activation in the pathogenesis of acute pancreatitis. Gut. 2008;57(2):259-67.
  • Hyun JJ, Lee HS. Experimental models of pancreatitis. Clin Endosc. 2014;47(3):212-6.
  • Lampel M, Kern HF. Acute interstitial pancreatitis in the rat induced by excessive doses of a pancreatic secretagogue. Virchows Arch A Pathol Anat Histol. 1977;373(2):97-117.
  • Saluja A, Saito I, Saluja M, Houlihan MJ, Powers RE, Meldolesi J, et al. In vivo rat pancreatic acinar cell function during supramaximal stimulation with caerulein. Am J Physiol. 1985;249(6 Pt 1):G702-10.
  • Zhao G, Vaszar LT, Qiu D, Shi L, Kao PN. Anti-inflammatory effects of triptolide in human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2000;11;279(5):L958-66.
  • Gray KD, Simovic MO, Chapman WC, Blackwell TS, Christman JW, Washington MK, et al. Systemic nf-kappaB activation in a transgenic mouse model of acute pancreatitis. J Surg Res. 2003;110(1):310-4.
There are 21 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Article
Authors

Hüseyin Özden 0000-0002-2786-3805

Asuman Kilitci 0000-0002-5489-2222

Yaşar Şahin 0000-0001-5936-4210

Gökhan Karaca 0000-0002-5107-5999

Haldun Umudum This is me 0000-0002-4550-1971

Ahmet Yıldız This is me 0000-0002-6889-4528

Erkan Dulkadiroğlu 0000-0001-7665-7453

Publication Date August 30, 2020
Submission Date April 29, 2020
Published in Issue Year 2020 Volume: 22 Issue: 2

Cite

APA Özden, H., Kilitci, A., Şahin, Y., Karaca, G., et al. (2020). Healing Effects of Single-Dose Triptolide in Rats with Severe Acute Pancreatitis. Duzce Medical Journal, 22(2), 105-108. https://doi.org/10.18678/dtfd.728067
AMA Özden H, Kilitci A, Şahin Y, Karaca G, Umudum H, Yıldız A, Dulkadiroğlu E. Healing Effects of Single-Dose Triptolide in Rats with Severe Acute Pancreatitis. Duzce Med J. August 2020;22(2):105-108. doi:10.18678/dtfd.728067
Chicago Özden, Hüseyin, Asuman Kilitci, Yaşar Şahin, Gökhan Karaca, Haldun Umudum, Ahmet Yıldız, and Erkan Dulkadiroğlu. “Healing Effects of Single-Dose Triptolide in Rats With Severe Acute Pancreatitis”. Duzce Medical Journal 22, no. 2 (August 2020): 105-8. https://doi.org/10.18678/dtfd.728067.
EndNote Özden H, Kilitci A, Şahin Y, Karaca G, Umudum H, Yıldız A, Dulkadiroğlu E (August 1, 2020) Healing Effects of Single-Dose Triptolide in Rats with Severe Acute Pancreatitis. Duzce Medical Journal 22 2 105–108.
IEEE H. Özden, A. Kilitci, Y. Şahin, G. Karaca, H. Umudum, A. Yıldız, and E. Dulkadiroğlu, “Healing Effects of Single-Dose Triptolide in Rats with Severe Acute Pancreatitis”, Duzce Med J, vol. 22, no. 2, pp. 105–108, 2020, doi: 10.18678/dtfd.728067.
ISNAD Özden, Hüseyin et al. “Healing Effects of Single-Dose Triptolide in Rats With Severe Acute Pancreatitis”. Duzce Medical Journal 22/2 (August 2020), 105-108. https://doi.org/10.18678/dtfd.728067.
JAMA Özden H, Kilitci A, Şahin Y, Karaca G, Umudum H, Yıldız A, Dulkadiroğlu E. Healing Effects of Single-Dose Triptolide in Rats with Severe Acute Pancreatitis. Duzce Med J. 2020;22:105–108.
MLA Özden, Hüseyin et al. “Healing Effects of Single-Dose Triptolide in Rats With Severe Acute Pancreatitis”. Duzce Medical Journal, vol. 22, no. 2, 2020, pp. 105-8, doi:10.18678/dtfd.728067.
Vancouver Özden H, Kilitci A, Şahin Y, Karaca G, Umudum H, Yıldız A, Dulkadiroğlu E. Healing Effects of Single-Dose Triptolide in Rats with Severe Acute Pancreatitis. Duzce Med J. 2020;22(2):105-8.