Skip to main content

Advertisement

Log in

Protective Effects of Baicalin and Octreotide on Multiple Organ Injury in Severe Acute Pancreatitis

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Purpose

To discuss the application value of Baicalin which is a new drug by comparing the protecting effects of Baicalin and Octreotide on multiple organs (pancreas, liver, kidney, and lung) in Severe acute pancreatitis (SAP).

Methods

The improved Aho method was adopted to prepare SAP rat models via retrograde injection of 3.5% sodium taurocholate to the pancreatic duct. The 135 SAP rat models after being prepared were randomly divided into the model group, Baicalin treatment group and Octreotide treatment group with 45 rats in each group; another 45 were selected to be the sham operation group, which only received abdomen opening surgery. The groups were then randomly divided into 3 h, 6 h and 12 h groups with 15 rats in each group, 10 min after successful modeling, the Baicalin treatment group was first injected with a 5% Baicalin injection at a dose of 10 mg/100 g via external jugular-vein passage followed by continuous intravenous administration (10 mg/h/100 g) by microinfusion pump; the Octreotide treatment group was first injected by Octreotide at a dose of 0.2 ug/100 g via external jugular-vein passage followed by continuous intravenous transfusion (10 mg/h/100 g) by microinfusion pump at a transfusion speed of 0.2 ug/h/100 g. The sham operation group and model group were injected with saline of equivalent volume at the corresponding time points after operation. The following observations were carried out 3, 6 and 12 h after operation: (1) mortalities of all rat groups followed by batch execution of rats and observation of the gross pathological changes of multiple organs; (2) observation of the pathological changes of multiple organ samples fixed according to the relevant requirements after HE staining; and (3) serum content of amylase, NO, malonaldehyde (MDA), and tumor necrosis factor alpha (TNF-α).

Results

(1) The survival rate of the sham operation group and all treatment groups was 100%, whilst the 12 h survival of the model group was 66.67% (10/15), indicating a significant difference (P < 0.05). (2) The gross pathological changes and changes under light microscopy of multiple organs aggravated with time after modeling. The pathological changes of all treatment groups were milder than those of the model group at different time points by various degrees, most obviously at 6 h and 12 h. The gross pathological changes showed a similarity between the Octreotide and Baicalin treatment groups in terms of the pathological changes of pancreatic tissue. The therapeutic effects of Octreotide on kidney and lung were superior to those in the Baicalin treatment group while the pathological manifestations of the Baicalin treatment group were superior to those of the Octreotide treatment group. (3) There was no marked difference between the Baicalin and Octreotide treatment groups in terms of plasma amylase levels at all time points (P > 0.05). Although the plasma amylase levels of the Baicalin treatment group were lower than those of the model group at all time points, the levels in the Baicalin treatment group were significantly lower than those in the model group only at 3 h (P < 0.05), and there was no marked difference in the levels between the Baicalin treatment group and model groups at 6 and 12 h (P > 0.05); the levels in the Octreotide treatment group were significantly lower than in the model group at 6 h (P < 0.05), and there was no marked difference between the levels in the Octreotide treatment group and model group at 3 h and 12 h (P > 0.05). (4) The serum NO contents of the Baicalin treatment group were significantly lower than those of the model group (P < 0.05), while in the Octreotide treatment group it was obviously lower than in the model group at 3 and 12 h (P < 0.01); in this regard there was no marked difference between the Baicalin and Octreotide treatment groups at different time points (P > 0.05). (5) The serum MDA contents of the Baicalin treatment group were significantly lower than those of the model group (P < 0.01), while in the Octreotide treatment group it was significantly less than the model group at 6 and 12 h (P < 0.05), and in the Baicalin treatment group was significantly less than in the Octreotide treatment group at 12 h (P < 0.05). (6) There was no marked difference among the model group, Baicalin treatment group and Octreotide treatment group in terms of serum TNF-α content at 3 h and 12 h (P > 0.05). At 6 h the value in the Baicalin treatment group was significantly less than in the model group (P < 0.001), in the Octreotide treatment group it was significantly less than in the model group (P < 0.001), and the Octreotide treatment group it was significantly less than in the Baicalin treatment group (P < 0.01).

Conclusions

Both Baicalin and Octreotide have obvious protective effects on the multiple organ injury in SAP with mechanisms associated to manifold factors. By comparing the pharmacologic effects of Octreotide and Baicalin, we believe that Baicalin as a new drug has a protective effect on multiple organs of a SAP rat model similar to that of Octreotide and is worth further study and development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Neurath MF, Becker C, Barbulescu K (1998) Role of NF-kappaB in immune and inflammatory responses in the gut. Gut 43(6):856–860 [PMID: 9824616]

    Article  PubMed  CAS  Google Scholar 

  2. Zhu AJ, Shi JS, Sun XJ (2003) Organ failure associated with severe acute pancreatitis. World J Gastroenterol 9(11):2570–2573 [PMID: 14606099]

    PubMed  Google Scholar 

  3. Lu ZL, Jia ZL, Liu XR (2005) Observation of clinical therapeutic effects of Octreotide on acute pancreatitis. Medical Forum Mag (Chinese) 26(9):17–19

    Google Scholar 

  4. Zhang J, Feng ZT, Zhou DQ (2004) Severe acute pancreatitis treated by Octreotide. Clinical Misdiagnosis and Mistherapy (Chinese) 17(1):11–12

    Google Scholar 

  5. LéiszlòCzakó, PéterHegyi,TamásTakács, CsabaGǒg, AndrásFarkas, YvetteMándy (2004) Effects of Octreotide on acute necrotizing pancreatitis in rabbits. World J Gastroenteol, 10(14):2082–2086. [PMID: 15237439]

  6. Saenko VF, Lupal’tsov VI, Babenkov GF, Kopchak VM, Volzhanskii AP (1999) The administration of sandostatin in the combined treatment of acute pancreatitis and its complications. Klin Khir 10:5–7 Russian [PMID: 10584505]

    PubMed  Google Scholar 

  7. van Ooijen B, Tinga CJ, Kort WJ, Zijlstra FJ, Lamberts SW, Wilson JH (1992) Effects of long-acting Somatostatin analog (SMS 201–995) on eicosanoid synthesis and survival in rats with acute necrotizing pancreatitis. Dig Dis Sci 37(9):1434–1440 [PMID: 1380426]

    Article  PubMed  Google Scholar 

  8. Cheng RC, Wang JZ, Ma WL, Diao C, Luo HY (2005) Protecting effects of Octreotide on rat hepatic cell apoptosis induced by pancreatitis related ascites. Chinese J Exp Surg 22(8):947–949

    Google Scholar 

  9. Yu X, Huang SF, Li YG, Zhang SD, Lei RQ, Han TQ (2003) Effects of Octreotide on pancreas pathological changes of acute pancreatitis rat and amylase secretion. Chinese J Modern Med 13(15):13–15

    CAS  Google Scholar 

  10. Zhang XP, Zhang L, Chen HQ, Cheng QH, Lu B, Ju TF, Fang X, Shen HP (2007) Study of protecting effects of Baicalin and Octreotide on heart injury in rats with severe acute pancreatitis(in Chinese). Chin J TCM WM Crit Care14(2):114–118

    CAS  Google Scholar 

  11. Hu C, Han JQ, Xu Z (2001) Influence of Baicalin on rat heptic cell apoptosis. China J Chinese Materia Medica 26(2):124–127

    CAS  Google Scholar 

  12. Liu CS, Ma LL, Li P (2001) Effects of Baicalin on erythrocyte aldose reductase activity and glomerular filtration rate of diabetics. China J Chinese Materia Medica 26(9):632–633

    CAS  Google Scholar 

  13. Wang CY, Fu FH, Tian JW, Zhang TP, Sun F, Liu K (2005) Protecting effects of Baicalin on chemical liver injury. Chinese Herbal Medicine (Chinese) 36(5):730–732

    CAS  Google Scholar 

  14. Zhang XP, Zhang L, He JX, Zhang RP, Cheng QH, Zhou YF, Lu B (2007) Experimental study of therapeutic efficacy of Baicalin in rats with severe acute pancreatitis. World J Gastroenterol 13(5):717–724 [PMID: 17278194]

    PubMed  CAS  Google Scholar 

  15. Zhang XP, Nie J, Feng GH, Lin NG, Cai Y, Jia PH, Wu YP, Zhen CL (2006) Application of tissue microarrays to study protecting effects of Baicalin and Octreotide on lung injury in severe acute pancreatitis (in Chinese). J Med Res 35(10):20–25

    CAS  Google Scholar 

  16. Hu C, Han JQ, Xu Z, Xiu HM, Liu JD, Hao Y (2001) Influence of Baicalin on rat liver cell apoptosis. China J Chinese Materia Medica 26(2):34–35

    Google Scholar 

  17. Liu IX, Durham DG, Richards RM (2000) Baicalin synergy with beta-lactam antibiotics against methicillin-resistant Staphylococcus aureus and other beta-lactam-resistant strains of S. aureus. J Pharm Pharmacol 52(3):361–366 [PMID: 10757427]

    Article  PubMed  CAS  Google Scholar 

  18. Yu Y, Yang YJ, Tao YG (2000) Influence of Baicalin/Dexamethasone on rat infectious cerebral edema cytokines. Bull of Hunan Medical University (Chinese) 25(6):519–521

    CAS  Google Scholar 

  19. Zhou XH, Zhai J, Ling YL (2001) Empirical study on Baicalin in resisting endotoxin shock. J Hebei Traditional Chinese Med and Pharmacol 16(1):32–33

    Google Scholar 

  20. Dygai AM, Suslov NI, Skurikhin EG, Churin AA, Provalova NV (1998) The modulating effects of preparations of Baikal skullcap (Scutellaria baicalensis) on erythron reactions under conditions of neurotic exposures. Eksp Klin Farmakol 61(1):37–39 Russian. [PMID: 9575410]

    PubMed  CAS  Google Scholar 

  21. Yin Y, Wu XD (2000) Regulation effect of Baicalin on rat immune function after myocardial infarction. J Nanjing Railway Medical College (Chinese) 19(3):162–164

    Google Scholar 

  22. Li BQ, Fu T, Dongyan Y, Mikovits JA, Ruscetti FW, Wang JM (2000) Flavonoid Baicalin inhibits HIV-1 infection at the level of viral entry. Biochem Biophys Res Commun 276(2):534–538 [PMID: 11027509]

    Article  PubMed  CAS  Google Scholar 

  23. Dui DH, Peng CJ, Gao ZF, Li YY (2003) Prevention and treatment effects of Qingyitang on severe acute pancreatitis complicated with endotoxemia of Xiang Pig. World Sci and Technol Modernization of Traditional Chinese Medicine and Materia Medica (Chinese) 5(4):31–35

    Google Scholar 

  24. Wu CT, Li ZL, Huang XC, Zhang ZL (1999) Comparative study on influence of Chinese medicine Qingyitang and Bacillus Bifidus composition on intestinal bacterial translocation in acute necrotizing pancreatitis. Shijie Huaren Xiaohua Zazhi 7(6)

  25. Li HZ, Zhang JJ, Li CY, Wang ZT, Zhao FS (2006) Clinical observation on severe acute pancreatitis treated by Qing Yi Tan combined with western medicine. Practical Clin J Integr Traditional Chinese and Western Medicine(Chinese) 6(1):10–10,60

    Google Scholar 

  26. Huang S (2005) Experiences from 26 cases of acute pancreatitis in adjunctive therapy of Qingyitang I. Guoji Yiyao Weisheng Daobao (in Chinese) 12(2):114–115

    Google Scholar 

  27. Qiu Y, Li YY, Li SG, Song BG, Zhao GF (2004) Effect of Qingyitang on activity of intracellular Ca2+-Mg2+-ATPase in rats with acute pancreatitis. World J Gastroenterol 10(1):100–104 [PMID: 14695778]

    PubMed  CAS  Google Scholar 

  28. Li YY, Li XL, Yang CX, Zhong H, Yao H, Zhu L (2003) Effects of Tetrandrine and QYT on ICAM-1 and SOD gene expression in pancreas and liver of rats with acute pancreatitis. World J Gastroenterol 9(1):155–159 [PMID: 12508373]

    PubMed  CAS  Google Scholar 

  29. Li YY, Gao ZF, Dui DH (2003) Therapeutic Effects of Qingyitang and Hanfang Jiasu on Severe acute pancreatitis of Xiang Pig and determination of plasma concentrations. Chinese J Integr Traditional and Western Med 23(11):832–836

    Google Scholar 

  30. Wen QP, Chen HL, Guan FL (2003) Observation on therapeutic effects of Qingyitang on acute lung injury in rat with severe acute pancreatitis. Chinese J Integr Traditional and Western Med 9(4):302–306

    Google Scholar 

  31. Yao GQ, Wu XZ (1997) Clinical Study on Qingyitang for treating severe acute pancreatitis. Chinese J Integr Traditional and Western Med 3(4):244–246

    Google Scholar 

  32. Qu CT, Li ZL, Huang XC, Zhang ZL (1999) Comparative study on influence of Chinese medicine Qingyitang and Bacillus Bifidus composition on intestinal bacterial translocation in acute necrotizing pancreatitis. Shijie Huaren Xiaohua Zazhi (Chinese) 7(6):525–528

    Google Scholar 

  33. Li JJ, Yang XJ, Wei MX (2002) Influence of Qingyitang on intestinal motility of rat with acute pancreatitis. Acta Universitatis Medicinalis Nanjing (Chinese) 22(3):223–225

    Google Scholar 

  34. Zhang XP, Tian H, Cheng QH (2003) Overview on pharmacological study of Baicalein. Chinese Pharmacological Bull 19(11):1212–1215

    CAS  Google Scholar 

  35. Park BK, Chung JB, Lee JH, Suh JH, Park SW, Song SY, Kim H, Kim KH, Kang JK (2003) Role of oxygen free radicals in patients with acute pancreatitis. World J Gastroenterol 9(10):2266–2269 [PMID: 14562390]

    PubMed  CAS  Google Scholar 

  36. Ran CM, Yi XL, Yi WJ (2004) Analysis on correlation between systemic inflammatory response syndrome and acute pancreatitis. Chinese J of General Surg 13(6):463–464

    Google Scholar 

  37. De Beaux AC, Goldie AS, Ross JA, Carter DC, Fearon KC (1996) Serum concentrations of inflammatory mediators related to organ failure in patients with acute pancreatitis. Br J Surg 83(3):349–353 [PMID: 8665189]

    Article  PubMed  Google Scholar 

  38. Wang XP, Lu Q (2000) Regulating effect of Octreotide on inflammatory mediators of acute necrotizing pancreatitis (in Chinese). Chin J Int Med 39(3):156–159

    Google Scholar 

  39. Zhang YQ, Zhou JY, Xu BH (1999) Antioxidation of Baicalin. Journal of Huazhong University of Science and Technology (Chinese) 27(4): 110–112

    Google Scholar 

  40. Dou YQ, Du LW, Xue Y, Chen HZ, Zhao ML (2005) Investigation on Baicalin for degrading bacterial endotoxin. Chinese J Hospital Pharm 25(7):683–684

    Google Scholar 

  41. Park BK, Chung JB, Lee JH, Suh JH, Park SW, Song SY, Kim H, Kim KH, Kang JK (2003) Role of oxygen free radicals in patients with acute pancreatitis. World J Gastroenterol 9(10):2266–2269 [PMID: 14562390]

    PubMed  CAS  Google Scholar 

  42. Lieberthal W (1998) Biology of ischemic and toxic renal tubular cell injury: role of nitric oxide and the inflammatory response. Curr Opin Nephrol Hypertens 7(3):289–295 Review. [PMID: 9617560 ]

    PubMed  CAS  Google Scholar 

  43. Zhu B, Sun JB, Zhang SW, Li F, Liu S, Cui YQ, Sun HC (2004) Effect of NF-κB activation and iNOS gene expression on acute pancreatitis lung injury. Chinese J Hepatobiliary Sur 10(4):248–251

    Google Scholar 

  44. Atsushi M,Tooru S,Akihiko S (2000) Nitri oxide decreases endothelial activitation by experimental severe pancreatitis-association ascetic fluids. Pancreas 20(3):297–304

    Article  Google Scholar 

  45. Ayub K, Serracino-Inglott F, Williamson RC, Mathie RT (2001) Expression of inducible nitric oxide synthase contributes to the development of pancreatitis following pancreatic ischaemia and reperfusion. Br J Surg 88(9):1189–1193 [PMID: 11531865]

    Article  PubMed  CAS  Google Scholar 

  46. Yang B, Huang HG, Chen DL (2002) NO changes in rat with severe acute pancreatitis. Chinese J Pancreatology 2(3):186–187

    Google Scholar 

  47. Wang J, Gong H, Wang Y (2003) Empirical study on Octreotide in preventing hepatic fibrosis formation. Chin J Hepatobiliary Surg (in Chinese) 9(2):100–102

    Google Scholar 

  48. Li XM, Wang JC, Li XL, Lu YJ (2005) Influence of Octreotide on liver and kidney lipid peroxidation of rat with multiple organ failure. Chinese J gerontology 25(10):1213–1215

    Google Scholar 

  49. Zhang Y, Song GH (2003) Protecting effect of scutellarin on kidney of diabetic rat. Chinese J Diabetes 11(5):324–326

    Google Scholar 

  50. Zuo GR (2005) Clinical observation on Octreotide in treating massive hemoptysis of pulmonary tuberculosis. Chinese J Modern Med 15(8):1252–1253

    Google Scholar 

  51. Urunuela A, Manso MA, de la Mano AM, de Dios I (2003) Cholecystokinin blockade triggers earlier and enhanced intra-acinar oxygen free radical generation in acute pancreatitis induced by pancreatic duct obstruction in rats. Clin Sci (Lond) 105(2):203–212 [PMID: 12713440]

    Article  CAS  Google Scholar 

  52. Ng TB, Liu F, Wang ZT (2000) Antioxidative activity of natural products from plants. Life Sci 66(8):709–723 [PMID: 10680579]

    Article  PubMed  CAS  Google Scholar 

  53. Hill DB, Devalaraja R, Joshi-Barre S et al (1999) Antioxidants attenuate nuclear factor-kappaB activation and tumor necrosis factor-alpha production in alcoholic hepatitis patient monocytes and rat kupffer cells, in vitro. Clin Biochem 32(7): 563–570

    Article  PubMed  CAS  Google Scholar 

  54. Satoh A, Shimosegawa T, Fujita M, Kimura K, Masamune A, Koizumi M, Toyota T (1999) Inhibition of nuclear factor-kappaB activation improves the survival of rats with taurocholate pancreatitis. Gut 44(2):253–258 [PMID: 9895386]

    Article  PubMed  CAS  Google Scholar 

  55. Zhang XP, Li ZF, Liu XG (2001) Overview on pharmacological study of Baicalein (in Chinese). Acta Pharmacologica Sinica 17(6):711–713

    CAS  Google Scholar 

  56. Shimizu I, Ma YR, Mizobuchi Y, Liu F, Miura T, Nakai Y, Yasuda M, Shiba M, Horie T, Amagaya S, Kawada N, Hori H, Ito S (1999) Effects of Sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats. Hepatology 29(1):149–160 [PMID: 9862861]

    Article  PubMed  CAS  Google Scholar 

  57. Xia Q, Yang XN, Gong X, Jiang JM, Hu WM (2004) Study on pathogenesis of acute necrotizing pancreatitis lung injury. J Hepatopancreatobiliary Surg 16(1):16–17

    Google Scholar 

  58. Bhatia M, Brady M, Shokuhi S, Christmas S, Neoptolemos JP, Slavin J (2000) Inflammatory mediators in acute pancreatitis. J Pathol 90(2):117–125 Review. [PMID: 10657008]

    Article  Google Scholar 

  59. Tome LA, Yu L, de Castro I, Campos SB, Seguro AC (1999) Beneficial and harmful effects of L-arginine on renal ischaemia. Nephrol Dial Transplant 14(5):1139–1145 [PMID: 10344352]

    Article  PubMed  CAS  Google Scholar 

  60. Cai HL, Qu ZM, Li QJ (2004) Octreotide in alleviating complications of severe acute pancreatitis patients. Modern Digestion & Intervention(Chinese) 9(1):17–19

    Google Scholar 

  61. Czako L, Hegyi P, Takacs T, Gog C, Farkas A, Mandy Y, Varga IS, Tiszlavicz L, Lonovics J (2004) Effects of Octreotide on acute necrotizing pancreatitis in rabbits. World J Gastroenterol, 10(14):2082–2086 [PMID: 15237439]

    PubMed  CAS  Google Scholar 

  62. Hao YL, Wen QS (2001) Study of Octreotide on acute necrotizing pancreatitis endothelin and oxygen free radica. Chinese J Global Med 21(12):695–696

    Google Scholar 

  63. Konturek PC, Dembinski A, Warzecha Z, Ceranowicz P, Konturek SJ, Stachura J, Hahn EG (1997) Expression of transforming growth factor-beta 1 and epidermal growth factor in caerulein-induced pancreatitis in rat. J Physiol Pharmacol 48(1):59–72 [PMID: 9098826]

    PubMed  CAS  Google Scholar 

  64. Bi XD, Zhang H (2003) Study progress on Octreotide in treating acute necrotizing pancreatitis. Medical Recapitulate (Chinese) 9(8):494–496

    Google Scholar 

  65. Xu YZ, Lu Q (2001) Effect of Octreotide on tumor necrosis factor α and no of empirical rats with acute necrotizing pancreatitis. Chinese J Gastroenterology and Hepatology 10(1):45–47

    Google Scholar 

  66. Black well TS, Christman TW (1997) Theroleo of nuclear factor-KB in cytokine gene regulation. Am J Respir Cell Mol Biol 17:3–9

    CAS  Google Scholar 

  67. Yu X, Zhang SD, Han TQ, Tang YQ, Lei RQ, Jiang ZH (2001) Regulating effect of Octreotide on blood prostaglandin level of rats with acute necrotizing pancreatitis. Chinese J Hepatobiliary Surg 7(3):12–13

    Google Scholar 

Download references

Acknowledgment

The authors are grateful to Chen Li and Tian Hua, whose institution is second affiliated hospital of School of Medicine, Zhejiang University, for their technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xi Ping Zhang.

Additional information

This work was supported by the technological foundation project of Traditional Chinese Medicine Science of Zhejiang province (nos. 2003C130 and 2004C142), the foundation project for medical science and technology of Zhejiang province (no. 2003B134), the grave foundation project for technological and development of Hangzhou (No. 2003123B19), intensive foundation project for technology of Hangzhou (no. 2004Z006), the foundation project for medical science and technology of Hangzhou (no. 2003A004), and the foundation project for technology of Hangzhou (No. 2005224). Note: We claim that the article is original and will not have any financial interest in a company or its competitor, and that all authors meet the criteria for authorship.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, X.P., Zhang, L., Yang, P. et al. Protective Effects of Baicalin and Octreotide on Multiple Organ Injury in Severe Acute Pancreatitis. Dig Dis Sci 53, 581–591 (2008). https://doi.org/10.1007/s10620-007-9868-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-007-9868-3

Keywords

Navigation