Gingerol inhibits cisplatin-induced vomiting by down regulating 5-hydroxytryptamine, dopamine and substance P expression in minks
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To investigate the antiemetic effect of gingerol and its multi-targets effective mechanism on 5-hydroxytryptamine (5-HT), dopamine (DA) and substance P (SP). The antiemetic effect of gingerol was investigated on a vomiting model of mink induced by cisplatin (7.5 mg · kg−1, i.p.) in 6 h observation. The levels of 5-HT, DA and distribution of substance P in the area postrema and ileum were measured by high performance liquid chromatography (HPLC) and immunohistochemistry respectively. The frequency of cisplatin induced retching and vomiting was significantly reduced by pretreatment with gingerol in a dose-dependent manner (P<0.05). Cisplatin produced a significant increase in 5-HT and DA levels in the area postrema and ileum of minks (P<0.05), and this increase was significantly inhibited by gingerol in a dose-dependent manner (P<0.05). Substance P-immunoreactive was mainly situated in the mucosa and submucosa of ileum as well as in the neurons of area postrema, and gingerol markedly suppressed the increase immunoreactivity of substance P induced by cisplatin in a dose-dependent manner (P<0.05). Gingerol has good activity against cisplatin-induced emesis in minks possibly by inhibiting central or peripheral increase of 5-HT, DA and substance P.
- Abali, H. and Celik, I., Tropisetron, ondansetron, and granisetron for control of chemotherapy-induced emesis in Turkish cancer patients: a comparison of efficacy, side-effect profile, and cost. Cancer Invest, 25, 135–139 (2007). CrossRef
- Abdel-Aziz, H., Windeck, T., Ploch, M. et al., Mode of action of gingerols and shogaols on 5-HT3 receptors: binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum. Eur J Pharmacol, 530, 136–143 (2006). CrossRef
- Andrews, P. L. R. and Bhandari, P., Resinferatoxin, an ultrapotent capsaicin analogue, has anti-emetic properties in the ferret. Neuropharmacology, 32, 799–806 (1993a). CrossRef
- Andrews, P. L. R. and Bhandari, P., The 5-hydroxytryptamine receptor antagonists as antiemetics: preclinical evaluation and mechanism of action. EurJ Cancer, 29(Suppl l), S11–S16 (1993b). CrossRef
- Andrews, P. L. R., Okada, F., Woods, A. J., Hagiwara, H., Kakaimoto, S., Toyoda, M., and Matsuki, N., The emetic and anti-emetic effects of the capsaicin analogue resiniferatoxin in, the Suncus murinus house musk shrew. Br J Pharmacol, 130, 1247–1254 (2000). CrossRef
- Andrews, P. L. R. and Rudd, J. A., The role of tachykinins and the tachykinin receptor in nausea and emesis. In Holzer, P. (Eds.), Handbook of Experimental Pharmacology. Springer-Verlag Berlin Heidelberg, Germany, pp. 359–440 (2004).
- Bountra, C., Bunce, K., Dale, T. J., Gardner, C. J., Jordan, C. C., Twissell, D. J., and Ward, P., Anti-emetic profile of a non-peptideneurokinin NK1 receptor antagonist, CP-99,994, in ferrets. Eur J. Pharmacol, 249, R3–R4 (1993). CrossRef
- Butler, A., Hill, J. M., Ireland, S. J., Jordan, C. C., and Tyers, M. B., Pharmacological properties of GR38032F, a novel antagonist at 5-HT3 receptors. Br J Pharmacol, 94, 397–412 (1988).
- Cubeddu, L. X., Serotonin mechanisms in chemotherapyinduced emesis in cancer patients. Oncology, 53(Suppl 1), 18–25 (1996). CrossRef
- Cubeddu, L. X., Hoffman, I. S., Fuenmayor, N. T. et al., Efficacy of ondansetron (GR 38032F) and the role of serotonin in cisplatin-induced nausea and vomiting. N Engl J Med, 322, 810–816 (1990). CrossRef
- Ferrier, C. M., de Witte, H. H., Straatman, H. et al., Comparison of immunohistochemistry with immunoassay (ELISA) for the detection of components of the plasminogen activation system in human tumour tissue. British Journal of Cancer, 79, 1534–154 (1999). CrossRef
- Diemunsch, P. and Grelot, L., Potential of substance P antagonists as antiemetics. Drugs, 60, 533–546 (2000). CrossRef
- Fiore, J. J. and Gralla, R. J., Pharmacologic treatment of chemotherapy-induced nausea and vomiting, Cancer Invest, 2, 351 (1984). CrossRef
- Grunberg, S. M. Hesketh, P. J., Control of chemotherapy-induced emesis. New Engl J Med, 329, 1790–1796 (1993). CrossRef
- Herrstedt, J., New perspectives in antiemetic treatment. Support Care Cancer, 4, 416–419 (1996). CrossRef
- Hesketh, P. J., Van Belle, S., Aapro, M., Tattersall, F. D., Naylor, R. J., Hargreaves, R., Carides, A. D., Evans, J. K., and Horgan, K. J., Differential involvement of neurotransmitters through the time course of cisplatin-induced emesis as revealed by therapy with specific receptor antagonists. Eur. J. Cancer, 39, 1074–1080 (2003). CrossRef
- Hickok, T. J. and Morrow, G. R., A biobehavioral model of patientreported nausea: implications for clinical practise. Adv. Med. Psychother, 6, 227 (1993).
- Jiang, S. Z., Mi, S. Z., and Wang, N. S., Survey of chemical constituents of gingerol. Traditional Chinese Drug Research & Clinical Pharmacology (in Chinese), 17, 386–389 (2006).
- Jordan, K., Kasper, C., and Schmoll, H. et al., Chemotherapy induced nausea and vomiting: current and new standards in the antiemetic prophylaxis and treatment. Eur J Cancer, 41, 199–205 (2005). CrossRef
- Kilpatrick, G. J., Jones, B. J., and Tyers, M. B., Binding of the 5-HT3 ligand, [3H]GR65630, to rat area postrema, vagus nerve and the brains of several species. Eur J Pharmacol, 159, 157–164 (1989). CrossRef
- King, G. L. and Landauer, M. R., Effects of zacopride and BMY25801 (batanopride) on radiation-induced emesis and loco-motor behavior in the ferret. J Pharmacol Exp Ther, 253, 1026–1033 (1990).
- Leksowski, K., Peryga, P., and Szyca, R., Ondansetron, metoclopramid, dexamethason, and their combinations compared for the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy: a prospective randomized study. Surg Endosc, 20, 878–882 (2006). CrossRef
- Leslie, R. A., Neuroactive substances in the dorsal vagal complex of the medulla oblongata: nucleus of the tractus solitarius, area postrema, and dosal motor nucleus of vagus. Neurochem Int., 7, 191–211 (1985). CrossRef
- Lucot, J. B., Blockade of 5-hydroxytryptamine3 receptors prevents cisplatin-induced but not motion- or xylazineinduced emesis in the cat. Pharmacol Biochem Behav, 32, 207–210 (1989). CrossRef
- Minami, M., Endo, T., and Hamaue, N. et al., Serotonin and anticancer drug-induced emesis. Surg Endosc, 124, 491–507 (2004).
- Nagashima, A., Takano, Y., Tateishi, K., Matsuoka, Y., Hamaoka, T., and Kamiya, H., Cardiovascular roles of tachykinin peptides in the nucleus tractus solitarii of rats. Brain Res, 487, 392–396 (1989). CrossRef
- Newton, B. W., Maley, B., and Traurig, H., The distribution of substance P, enkephalin and serotonin immunoreactivities in the area postrema of the rat and cat. J. Comp. Neurol, 234, 87–104 (1985). CrossRef
- Ramírez, M. J., Cenarruzabeitia, E. R. J. D., and Lashera, B., Involvement of neurokinins in the non-cholinergic response to activation of 5-HT3- and 5-HT4-receptors in guinea pig ileum. Br. J. Pharmacol, 111, 419–424 (1994).
- Rudd, J. A. and Andrews, P. L. R., Mechanisms of acute, delayed, and anticipatory emesis induced by anticancer therapies, In P.J. Hesketh (Eds.), Management of Nausea and Vomiting in Cancer and Cancer Treatment, Jones and Barlett Publishers, Inc., USA, pp 15–66 (2004).
- Round, A. and Wallis, D. I., The depolarizing action of 5-hydroxy-tryptamine on rabbit vagal afferent and sympathetic neurones in vitro and its selective blockade by ICS 205–930. Br J Pharmacol, 88, 485–494 (1986).
- Pongrojpaw, D. et al., The efficacy of ginger in prevention of post-operative nausea and vomiting after outpatient gynecological laparoscopy. J. Med. Assoc. Thai, 3, 244–250 (2003).
- Potts, J. T., Fuchs, I. E., Li, J., Leshnower, B., and Mitchell, J. H., Skeletal muscle afferent fibres release substance P in the nucleus tractus solitarii of anaesthetized cats. Journal of Physiology, 514, 829–841 (1999). CrossRef
- Rudd, J. A. and Andrews, P. L. R., Mechanisms of acute, delayed and anticipatory vomiting in cancer and cancer treatment. In Hesketh, P. (Eds.), Management of Nausea and Vomiting in Cancer and Cancer Treatment. Jones and Barlett Publishers Inc., New York, pp 15–66 (2004).
- Sharma, S. S. et al., Antie metic effcacy of ginger against cisplatin induced emsis in dogs. Ethnonharmacol, 2, 93–96 (1997). CrossRef
- Surh, Y. J., Anti-tumor promoting potential of selected spice ingredients with antioxidative and anti-inflammatory activities: a short review. Food Chem Toxicol, 40, 1091–1097 (2002). CrossRef
- Tattersall, F. D., Rycroft, W., Hill, R. G., and Hargreaves, R. J., Enantioselective inhibition of apomorphine-induced emesis in the ferret by the neuokinin1 receptor antagonist CP-99,994, Neuropharmacology, 33, 259–260 (1994). CrossRef
- Van Belle, S., Lichinitser, M. R., and Navari, R. M. et al., Prevention of cisplatin-induced acute and delayed emesis by the selective neurokinin-1 antagonists, L-758,298 and MK-869. Cancer, 94, 3032–3041 (2002). CrossRef
- Watson, J. W., Gonsalves, S. F., Fossa, A. A., McLean, S., Seeger, T., Obach, S., and Andrews, P. L. R., The antiemetic effects of CP-99,994 in the ferret and dog: role of the NK1 receptor. Br. J. Pharmacol, 115, 84–94 (1995).
- Vutyavanich, T. et al., Ginger for nausea and vomiting in pregnancy: randomized double-masked placebo-controlled trial. Obstetrics and Gynecology, 4, 577–582 (2001). CrossRef
- Zhang, F., Wang, L., Yang, Z. H. et al., Value of mink vomit model in study of anti-emetic drugs. World J Gastroenterol, 12, 1300–1302 (2006).
- Zhao, D.-x., Yang, Z.-h., Li, M., Xue, M., and Yue, W., Anti-emetic effects of ginger on a nausea model of mink. Chinese Pharmaceutical Affairs (in Chinese), 10, 601–604 (2006).
- Gingerol inhibits cisplatin-induced vomiting by down regulating 5-hydroxytryptamine, dopamine and substance P expression in minks
Archives of Pharmacal Research
Volume 32, Issue 4 , pp 565-573
- Cover Date
- Print ISSN
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- Pharmaceutical Society of Korea
- Additional Links
- Substance P
- Industry Sectors
- Author Affiliations
- 1. Pharmic Department, Medical College of Qingdao University, Qingdao, Shandong, 266021, China
- 2. Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250011, China