Browse > Article

Effects of Ijintang-gamibang on the Rat Chronic Cisplatin-induced Delayed Gastrointestinal Motility  

Kim, Dae Jun (3rd Department of Internal Medicine, College of Korean Medicine, Daegu Haany University)
Publication Information
Journal of Physiology & Pathology in Korean Medicine / v.27, no.2, 2013 , pp. 225-232 More about this Journal
Abstract
Delayed gastrointestinal (GI) motility is frequent adverse effect associated with chemotherapy, and induced by serotonin releases from enterochromaffin cells. Ijintang-gamibang (IJG) is a digestive polyherbal formula has been traditionally used in Korea and consisted of 8 types of medicinal herbs. This study was conducted to determine whether or not IJG aqueous extracts can prevent delayed GI motility induced by the antineoplastic drug cisplatin chronically administered, once per week for five consecutive weeks (2 mg/kg). 200, 100 and 50 mg/kg of IJG extracts were orally administered, once a day for 14 days from fourth cisplatin treatment, and the changes in body weight gain, fecal parameters, gastrointestinal transit ratio and histopathology were observed. In addition, pylorus gastrin and serotonin contents were also measured with immunohistochemical observations of enterochromaffin cells contains gastrin and serotonin, as compared with ondansetron, a serotonin 5-HT3 receptor antagonist, 1 mg/kg. Cisplatin treatment related body weight decreases, delayed GI motility, decreases of fecal water contents were significantly and dose-dependently inhibited by oral treatment of IJG extracts, and they also inhibited the pylorus gastrin and serotonin changes induced by cisplatin treatment. The overall effects of IJG 100 mg/kg were similar to that of ondansetron 1 mg/kg. The present results supported that IJG aqueous extracts have favorable ameliorating effect on the delayed GI motility induced by chemotheraphy, modulated the GI enterochromaffin cells, serotonin and gastrin-producing cells with antioxidant effects. This effect of IJG may help improve accompanying gastrointestinal symptoms by chemotherapy.
Keywords
Ijintang-gamibang; chemotherapy; delayed gastrointestinal motility; serotonin; gastrin;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Visnovsky, P. The effect of cyclophosphamide and methotrexate on gastric emptying and secretion in rats. Bratisl Lek Listy. 93(2):90-82, 1992.
2 Yoshida, N., Omoya, H., Ito, T. DAT-582, a novel serotonin3 receptor antagonist, is a potent and long-lasting antiemetic agent in the ferret and dog. J Pharmacol Exp Ther. 260(3):1159-1165, 1992.
3 Kishibayashi, N., Ichikawa, S., Yokoyama, T., Ishii, A., Karasawa, A. Pharmacological properties of KF18259, a novel 5-HT3-receptor antagonist, in rats: inhibition of the distal colonic function. Jpn J Pharmacol 63(4):495-502, 1993.   DOI
4 Lebwohl, D., Canetta, R. Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. Eur J Cancer. 34(10):1522-1534, 1998.   DOI   ScienceOn
5 Sassi, G., Striano, B., Merlo, U.A. A reporting system for the assessment of chemotherapy toxicity. J Oncol Pharm Pract. 11(2):63-67, 2005.   DOI   ScienceOn
6 Bradner, W.T., Schurig, J.E. Toxicology screening in small animals. Cancer Treat Rev. 8(2):93-102, 1981.   DOI   ScienceOn
7 Kilpatrick, G.J., Bunce, K.T., Tyers, M.B. 5-HT3 receptors. Br J Cancer. 58: 651-653, 1990.
8 Tyers, M.B. 5-HT3 receptors and the therapeutic potential of 5-HT3 receptor antagonists. Therapie (Paris), 46(6):431-435, 1991.
9 Roos, I.A., Fairlie, D.P., Whitehouse, M.W. A peculiar toxicity manifested by platinum(II)amines in rats: gastric distension after intraperitoneal administration. Chem Biol Interact. 35(1):111-117, 1981.   DOI   ScienceOn
10 Sharma, S.S., Gupta, Y.K. Reversal of cisplatin-induced delay in gastric emptying in rats by ginger (Zingiber officinale). J Ethnopharmacol. 62(1):49-55, 1998.   DOI   ScienceOn
11 Minami, M., Endo, T., Hirafuji, M., Hamaue, N., Liu, Y., Hiroshige, T., Memoto, M., Saito, H., Yoshioka,, M. Pharmacological aspects of anti-cancer drug-induced emesis with emphasis on serotonin release and vagal nerve activity. Pharmacol Ther. 99(2):149-165, 2003.   DOI   ScienceOn
12 Milne, R.J., Heel, R.C. Ondansetron: therapeutic use as an antiemetic. Drugs. 41(4):574-595, 1991.   DOI   ScienceOn
13 Beck, T.M., Ciociola, A.A., Jones, S.E., Harvey, W.H., Tchekmedyian, N.S., Chang, A., Galvin, D., Hart, N.E. Efficacy of oral ondansetron in the prevention of emesis in outpatients receiving cyclophosphamide-based chemotherapy. The Ondansetron Study Group. Ann Intern Med. 118(6):407-413, 1993.   DOI   ScienceOn
14 Scuderi, P., Wetchler, B., Sung, Y.F., Mingus, M., DuPen, S., Claybon, L., Leslie, J., Talke, P., Apfelbaum, J., Sharifi-Azad, S., et al. Treatment of postoperative nausea and vomiting after outpatient surgery with the 5-HT3 antagonist ondansetron. Anesthesiology. 78(1):15-20, 1993.   DOI   ScienceOn
15 Martin, C., Roman, V., Agay, D,, Fatôme, M. Anti-emetic effect of ondansetron and granisetron after exposure to mixed neutron and gamma irradiation. Radiat Res. 149(6):631-636, 1998.   DOI
16 Miyata, K., Yamano, M., Kamato, T., Akuzawa, S. Effect of serotonin (5-HT)3-receptor antagonists YM060, YM114 (KAE-393), ondansetron and granisetron on 5-HT4 receptors and gastric emptying in rodents. Jpn J Pharmacol. 69(3):205-214, 1995.   DOI
17 Malik, N.M., Liu, Y.L., Cole, N., Sanger, G.J., Andrews, P.L. Differential effects of dexamethasone, ondansetron and a tachykinin NK1 receptor antagonist (GR205171) on cisplatin-induced changes in behaviour, food intake, pica and gastric function in rats. Eur J Pharmacol. 555(2-3):164-173, 2007.   DOI   ScienceOn
18 許浚, 東醫寶鑑, 경남, 동의보감 출판사, p 1235, 2005.
19 McKechnie, K., Froese, A. Ventricular tachycardia after ondansetron administration in a child with undiagnosed long QT syndrome. Can J Anaesth. 57(5):453-457, 2010.   DOI
20 Hafermann, M.J., Namdar, R., Seibold, G.E., Page, R.L. 2nd. Effect of intravenous ondansetron on QT interval prolongation in patients with cardiovascular disease and additional risk factors for torsades: a prospective, observational study. Drug Healthc Patient Saf. 3: 53-58, 2011.
21 황지영, 김대준, 변준석. 역류성 식도염에 대한 이진탕가미방 효과연구. 동의생리병리학회지 23(5):1073-1079, 2009.
22 박경, 곽민아, 김대준, 변준석. 이진탕가미방(二陳湯加味方)의 항산화 효과를 통한 역류성 식도염 억제효과. 동의생리병리학회지 24: 416-425, 2010.
23 오중한, 김봉석, 임희용, 김동우, 최빈혜, 허진일, 김대준, 조종관, 변준석. 이진탕가미방 투여 후 호전된 기능성 소화불량 환자 3례에 대한 증례 보고. 대한한방내과학회지 26(3):641-651, 2005.
24 김봉석, 임희용, 오중한, 김동우, 최빈혜, 허진일, 김대준, 변준석. 이진탕가미방과 침치료를 병행한 비미란성 위식도역류질환 환자 7인 증례보고. 대한한방내과학회지 26(4):926-934, 2005.
25 김대준. 이진탕가미방의 마우스 경구 단회 투여독성평가. 동의생리병리학회지 24(6):1019-1026, 2010.
26 Vera, G., Chiarlone, A., Cabezos, P.A., Pascual, D., Martín, M.I., Abalo, R. WIN 55, 212-2 prevents mechanical allodynia but not alterations in feeding behaviour induced by chronic cisplatin in the rat. Life Sci. 81: 468-479, 2007.   DOI   ScienceOn
27 김희준, 임소연, 곽민아, 김대준, 변준석. 역류성식도염 유발 흰쥐에 대한 이진탕가미방(二陳湯加味方)의 효과. 대한한방내과학회지 31: 128-141, 2010b.
28 Endo, T., Takahashi, M., Minami, M., Yoshioka, M., Saito, H., Parvez, S.H. Effects of anticancer drugs on enzyme activities and serotonin release from ileal tissue in ferrets. Biog Amines. 9: 479-489, 1993.
29 Sagar, L., Sehgal, R., Ojha, S. Evaluation of antimotility effect of Lantana camara L. var. acuelata constituents on neostigmine induced gastrointestinal transit in mice. BMC Complement Altern Med. 17(5):18, 2005.
30 Wintola, O.A., Sunmonu, T.O., Afolayan, A.J. The effect of Aloe ferox Mill. in the treatment of loperamide-induced constipation in Wistar rats. BMC Gastroenterol. 29(10):95, 2010.
31 Ju, C., Hamaue, N., Machida, T., Liu, Y., Iizuka, K., Wang, Y., Minami, M., Hirafuji, M. Anti-inflammatory drugs ameliorate opposite enzymatic changes in ileal 5-hydroxytryptamine metabolism in the delayed phase after cisplatin administration to rats. Eur J Pharmacol. 589(1-3):281-287, 2008.   DOI   ScienceOn
32 Ku, S.K., Seo, B.I., Park, J.H., Park, G.Y., Seo, Y.B., Kim, J.S., Lee, H.S., Roh, S.S. Effect of Lonicerae Flos extracts on reflux esophagitis with antioxidant activity. World J Gastroenterol. 15(38):4799-4805, 2009.   DOI   ScienceOn
33 Park, S.Y., Ku, S.K., Lee, E.S., Kim, J.A. 1,3-Diphenylpropenone ameliorates TNBS-induced rat colitis through suppression of NF-${\kappa}B$ activation and IL-8 induction. Chem Biol Interact 196(1-2):39-49, 2012.   DOI   ScienceOn
34 Lee, H.S., Choi, S.H., Ku, S.K. Regional distribution and relative frequency of gastrointestinal endocrine cells in the ddN mice: an immunohistochemical study. Anat Histol Embryol 39(6):521-528, 2010.   DOI   ScienceOn
35 Levene, A. Pathological factors influencing excision of tumours in the head and neck. Part I. Clin Otalary 6(3):145-151, 1981.   DOI
36 Wang, Y., Aggarwal, S.K., Kopachik, W. Role of vitamin d on the inhibition of gastrin production after Cisplatin treatment. Met Based Drugs 7(3):115-119, 2000.   DOI   ScienceOn
37 Ludbrook, J. Update: microcomputer statistics packages. A personal view. Clin Exp Pharmacol Physiol. 24(3-4):294-296, 1997.   DOI   ScienceOn
38 이형식, 구세광, 이재현. 한국재래산양 태자의 위장관에서 Serotonin 면역반응세포의 분포 및 출현빈도에 관한 연구. 기초과학. 2(2):107-116, 1998.
39 Wang, Y., Aggarwal, S.K. Effects of cisplatin and taxol on inducible nitric oxide synthase, gastrin and somatostatin in gastrointestinal toxicity. Anticancer Drugs 8(9):853-858, 1997.   DOI