Department of Comparative Pathophysiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
J Toxicol Sci. 2011 Jan;36(1):23-9. doi: 10.2131/jts.36.23.
Nausea and emesis are often observed as side effects with many medicines and may lead to poor treatment compliance. In the present study, we aimed to establish simple methods for predicting nausea and/or emesis in mice, which do not vomit, using drugs and chemicals known to evoke nausea and/or emesis. The gastrointestinal transit test, the liquid gastric emptying by phenol red solution (Phenol red method) and the solid gastric emptying by resin beads (Beads method) were used and the effects of antispasmogenics (atropine, 0.1-3 mg/kg i.p.; salmon calcitonin, 1-30 units/kg i.m.), nauseants (copper sulfate, 1-30 mg/kg p.o.; apomorphine, 0.01-0.3 mg/kg s.c.) and chemotherapeutics (cisplatin, 0.3-10 mg/kg i.v.; doxorubicin, 0.3-10 mg/kg i.v.) were evaluated. In addition, the effects of ondansetron, a serotonin (5-HT)(3) receptor antagonist, on the inhibition of solid gastric emptying induced by salmon calcitonin, copper sulfate, cisplatin and doxorubicin were also assessed. Only the solid gastric emptying method could detect changes of gastric emptying by all drugs and chemicals. We also found that the inhibition of solid gastric emptying induced by cisplatin and doxorubicin was dose-dependently antagonized by ondansetron. However, ondansetron failed to antagonize the salmon calcitonin-induced delay, but exerted only very weak effects with copper sulfate. Solid gastric emptying may be more suitable than gastrointestinal intestinal transit or liquid gastric emptying in mice to predict nausea and/or emesis. Our results also suggest that chemotherapeutic-induced delay of solid gastric emptying mediated via 5-HT(3) receptors in mice could also be useful for prediction purposes.
恶心和呕吐是许多药物常见的副作用，可能导致治疗依从性差。在本研究中，我们旨在建立简单的方法来预测不呕吐的小鼠的恶心和/或呕吐，使用已知可引起恶心和/或呕吐的药物和化学物质。我们使用了胃肠道转运试验、酚红溶液（酚红法）的液体胃排空和树脂珠（珠子法）的固体胃排空，并评估了抗痉挛药物（阿托品，0.1-3mg/kg 腹腔注射；鲑鱼降钙素，1-30 单位/kg 肌肉注射）、催吐剂（硫酸铜，1-30mg/kg 口服；阿扑吗啡，0.01-0.3mg/kg 皮下注射）和化疗药物（顺铂，0.3-10mg/kg 静脉注射；多柔比星，0.3-10mg/kg 静脉注射）的作用。此外，我们还评估了 5-HT（3）受体拮抗剂昂丹司琼对鲑鱼降钙素、硫酸铜、顺铂和多柔比星诱导的固体胃排空抑制的影响。只有固体胃排空方法才能检测所有药物和化学物质引起的胃排空变化。我们还发现，昂丹司琼可剂量依赖性拮抗顺铂和多柔比星诱导的固体胃排空抑制。然而，昂丹司琼未能拮抗鲑鱼降钙素引起的延迟，但对硫酸铜只发挥了非常弱的作用。与胃肠道转运或液体胃排空相比，固体胃排空在预测恶心和/或呕吐方面可能更合适。我们的结果还表明，5-HT（3）受体介导的化疗药物诱导的固体胃排空延迟在小鼠中也可能具有预测作用。
