• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.149-153
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• 2014

Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7701-7706
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• 2013

Background: In a prospective cohort study of antiemetic therapy conducted in Malaysia, a total of 94 patients received low emetogenic chemotherapy (LEC) with or without granisetron injections as the primary prophylaxis for chemotherapy-induced nausea and vomiting (CINV). This study is a retrospective cost analysis of two antiemetic regimens from the payer perspective. Materials and Methods: This cost evaluation refers to 2011, the year in which the observation was conducted. Direct costs incurred by hospitals including the drug acquisition, materials and time spent for clinical activities from prescribing to dispensing of home medications were evaluated (MYR 1=$0.32 USD). As reported to be significantly different between two regimens (96.1% vs 81.0%; p=0.017), the complete response rate of acute emesis which was defined as a patient successfully treated without any emesis episode within 24 hours after LEC was used as the main indicator for effectiveness. Results: Antiemetic drug acquisition cost per patient was 40.7 times higher for the granisetron-based regimen than for the standard regimen (MYR 64.3 vs 1.58). When both the costs for materials and clinical activities were included, the total cost per patient was 8.68 times higher for the granisetron-based regimen (MYR 73.5 vs 8.47). Considering the complete response rates, the mean cost per successfully treated patient in granisetron group was 7.31 times higher (MYR 76.5 vs 10.5). The incremental cost-effectiveness ratio (ICER) with granisetron-based regimen, relative to the standard regimen, was MYR 430.7. It was found to be most sensitive to the change of antiemetic effects of granisetron-based regimen. Conclusions: While providing a better efficacy in acute emesis control, the low incidence of acute emesis and high ICER makes use of granisetron as primary prophylaxis in LEC controversial.

• Journal of Haehwa Medicine
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• v.26 no.1
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• pp.25-32
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• 2017

Objectives : The purpose of this study is to investigate the effects of Hyangsayangwi-tang (Xiangshayangwei-tang) intravenous herbal acupuncture (HYT-IVHA) on emesis and gastric hypomotility induced by chemotherapy in rats. Methods : The experimental animals were randomly allocated into six groups (normal, cisplatin, saline, HYT-1, HYT-2, HYT-3), and each group included five rats. The rats in the normal group did not receive any treatment. Those in the cisplatin group had no additional treatment after intraperitoneal injection of cisplatin (7 mg/kg). Those in the saline group were injected with saline $0.4m{\ell}$ via the tail vein after the injection of cisplatin. Those in the HYT-1 group, HYT-2 group, HYT-3 group were injected with $0.4m{\ell}$ of Hyangsayangwi-tang (Xiangshayangwei-tang) intravenous herbal acupuncture solution (HYT-IVHAS) via tail vein after the injection of cisplatin, and the concentrations were 0.199 g/kg, 0.066 g/kg, 0.022 g/kg respectively. Then we measured body weight, food intake and kaolin consumption before and at 12h, 24h and 36h after the injection of cisplatin. The remaining amount of food within the rat's stomach was also measured at 36h after cisplatin injection. Results : Kaolin consumption was significantly increased in the cisplatin group compared to the normal group, while significantly reduced in HYT-1, HYT-2, HYT-3 groups compared to the cisplatin group. The remaining amount of food in stomach was significantly increased in the cisplatin group and HYT-1 group compared to the normal group, but significantly reduced in the HYT-3 group compared to the cisplatin group. Conclusions : HYT-IVHA has an therapeutic effect on chemotherapy-induced emesis and gastric hypomotility.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.114-114
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• 2002

Inhibitors of type IV phosphodiesterase (PDE IV) are currently being developed as new therapeutic agents for asthma, chronic obstructive pulmonary disease(COPD) and arthritis. Unfortunately, the anti-inflammatory effect of PDE IV inhibitors has been considered to be associated to some extent with vomiting as adverse effect. The first generation PDE IV inhibitor, rolipram, was known to induce emesis at clinical trials. (omitted)

• Journal of Acupuncture Research
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• v.34 no.3
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• pp.39-48
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• 2017

Objectives : The objective of this study was to evaluate the effect of Dokhwaljihwang-tang (DJT) intravenous pharmacopuncture on cisplatin-induced emesis and gastric mobility disorder in Wistar rats. Methods : Thirty rats were randomly divided into six groups and cisplatin was administered to all groups except the normal group. The cisplatin group (n=5) received a cisplatin injection only. The saline group (n=5) was injected with cisplatin followed by 0.4 mL of saline. Groups DJT-1, DJT-2, and DJT-3 were injected with cisplatin, followed by 0.315 g/kg, 0.104 g/kg, and 0.034 g/kg of DJT, respectively. Body weight, food intake, and kaolin intake of rats were measured 12 h, 24 h, and 36 h after cisplatin injection. Residual food in the stomach was measured 48 h after cisplatin injection. Results : There was no significant difference in weight. The food intake was not significantly different 12 h after cisplatin administration. All groups except the normal group showed significantly decreased food intake after 24 h. After 36 h, food intake was not significantly different between groups DJT-1, DJT-2, and DJT-3 and the normal group. The kaolin intake of groups DJT-1 and DJT-2 was significantly decreased at 12 h and 24 h after cisplatin injection. Kaolin intake and residual food in the stomach were significantly decreased in groups DJT-1, DJT-2, and DJT-3. Conclusion : In a Wistar rat model, DJT intravenous pharmacopuncture is suggested to be effective for cisplatin-induced emesis and gastric motility disorder. In the future, it is necessary to study the mechanism and chemical composition of each individual constitutive drug.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.469-473
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• 2013

Background: The purpose of this study is to examine the risk of uncontrolled chemotherapy-induced nausea and vomiting (CINV) among patients receiving low emetogenic chemotherapy (LEC) with and without granisetron injection as the primary prophylaxis in addition to dexamethasone and metochlopramide. Materials and Methods: This was a single-centre, prospective cohort study. A total of 96 patients receiving LEC (52 with and 42 without granisetron) were randomly selected from the full patient list generated using the e-Hospital Information System (e-His). The rates of complete control (no CINV from days 1 to 5) and complete response (no nausea or vomiting in both acute and delayed phases) were identified through patient diaries which were adapted from the MASCC Antiemesis Tool (MAT). Selected covariates including gender, age, active alcohol consumption, morning sickness and previous chemotherapy history were controlled using the multiple logistic regression analyses. Results: Both groups showed significant difference with LEC regimens (p<0.001). No differences were found in age, gender, ethnic group and other baseline characteristics. The granisetron group indicated a higher complete response rate in acute emesis (adjusted OR: 0.1; 95%CI 0.02-0.85; p=0.034) than did the non-granisetron group. Both groups showed similar complete control and complete response rates for acute nausea, delayed nausea and delayed emesis. Conclusions: Granisetron injection used as the primary prophylaxis in LEC demonstrated limited roles in CINV control. Optimization of the guideline-recommended antiemetic regimens may serve as a less costly alternative to protect patients from uncontrolled acute emesis.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.449-457
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• 2015

The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents.

• Korean Journal of Veterinary Research
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• v.45 no.2
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• pp.297-302
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• 2005

The present experiment was performed in order to know the anti-emetic effect of acupuncture, aquapuncture with metoclopramide and moxibustion on the xylazine induced emesis in dogs. The animals were devided into a control group (non-acupoint) and two experimental groups (BL-20 and LIV-13), respectively. Acupuncture, aquapuncture with metoclopramide (1 mg/kg) and moxibustion were applied to animals for 20 minutes before xylazine injection (2.2 mg/kg, IM). In acupuncture group, the emetic rates in BL-20 (16.7%) and LIV-13 (16.7%) were lower than that of control group (50%), respectively. In aquapuncture group, the emetic rates in BL-20 (16.7%) and LIV-13 (0.0%) were lower than that of control group (50%), respectively. In moxibustion group, the emetic rates in BL-20 (50%) and LIV-13 (16.7%) were lower than that of control group (83.3%), respectively. Considering above the findings collectively, it is considered that acupuncture, aquapuncture with metoclopramide and moxibustion at BL-20 and LIV-13 are effective and especially aquapuncture with metoclopramide at LIV-13 is the most effective treatment to prevent the emesis induced by xylazine among groups.

• Korean Journal of Veterinary Research
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• v.45 no.3
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• pp.399-403
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• 2005

This study was performed to elucidate the effect of acupuncture and aqua-acupuncture in dogs. Each group was divided into control (18 dogs), PC-6 (6 dogs) and BL-21 (6 dogs) group for the antiemetic effect of acupuncture, respectively. And, the animals were divided into control (18 dogs), PC-6 (18 dogs) and BL-21 (18 dogs) group for the antiemetic effect of aqua-acupuncture with metoclopramide, respectively. 2% xylazine was injected to the all dogs to induce the emesis, and acupuncture and aqua-acupuncture treatment (0.5% metoclopramide) were applied to animals for 20 min. before xylazine injection, respectively. Emetic rates in PC-6 (33.3%) and BL-21 (16.7%) were lower than that of control group (44.4%) in acupuncture groups, respectively. Emetic rates in PC-6 (16.7%) and BL-21 (0.0%) were lower than that of control group (38.9%) in aqua-acupuncture groups, respectively. Based on these findings, it was considered that the antiemetic effects of acupuncture and aqua-puncture at BL-21 were more effective than those of PC-6 groups, and aqua-acupuncture with metoclopramide at BL-21 was the most effective among them.

• Toxicological Research
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• v.17 no.2
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• pp.159-161
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• 2001

The anti-emetic effect of a 5-HT$_3$ receptor antagonist, Ondaron, was compared with that of the approved ondansetron agent, Zofran$\circledR$ in the ferrets. Emesis was induced by single intraperitoneal injection of cisplatin 10 mg/kg, and Ondaron or Zofran$\circledR$ was injected intraperitoneally in a dose of 1.0 mg/kg, respectively. Ondaron and Zofran$\circledR$ effectively antagonised the emetic response for 4 hours after injection. They significantly reduced the number of vomiting and retching, and prolonged the latency to the first episode. The anti-emetic effect of Ondaron was almost the equal to that of Zofran$\circledR$. These results suggest that Ondaron is an effective anti-emetic agent against cisplatin-induced emesis, and its anti-emetic potency is similar to that of 5-$HT_3$ receptor abtagonist, Zofran$\circledR$.