Abstract
Xiao-Ban-Xia-Tang (XBXT), a traditional Chinese medicine formula, has been used for the treatment of emesis for nearly 2000 years, but its underlying mechanism is not yet fully clarified. The purpose of this study is to reveal the antiemetic mechanisms of XBXT by focusing on the NLRP3 inflammasome pathway in a chemotherapy-induced rat pica model. The pica model was generated by a single intraperitoneal injection of cisplatin in this study. Consumption of kaolin (a type of clay) and food and body weight were recorded every 24 hours. Cisplatin-induced increase in kaolin consumption (pica) was used to quantify chemotherapy-induced nausea and vomiting (CINV). Tissue from the ileum and antrum was stained with hematoxylin eosin (HE) to observe pathological changes. The levels of reactive oxygen species (ROS) and inflammatory cytokines, including IL-1β and IL-18 in serum, were detected by ELISA. In addition, changes in the NLRP3 inflammasome activation in the ileum and antrum were investigated using western blot and immunofluorescence microscopy. The results showed that oral administration of XBXT and ondansetron inhibited acute and delayed pica and significantly protected against the gastrointestinal pathological injury induced by cisplatin. The levels of ROS, IL-1β, and IL-18 in the serum of cisplatin-treated rats were also remarkably decreased by XBXT and ondansetron. Moreover, we found that XBXT can inhibit cisplatin-induced NLRP3 inflammasome activation. The present study indicates that the inhibition of the NLRP3 inflammasome activation might be one of the potential mechanisms for the therapeutic effects of XBXT against CINV.
Highlights
Chemotherapy-induced nausea and vomiting (CINV) is among the most debilitating and distressing events in cytotoxic chemotherapy [1]. e emetic response to chemotherapy is classified into acute phase and delayed phase [2]
For the treatment of nausea and vomiting in patients receiving high-emetic chemotherapy (HEC), the European Society of Medical Oncology (ESMO) and the Multinational Association of Supportive Care in Cancer (MASCC) guidelines [4] recommend a combination of a 5-hydroxytryptamine type 3 receptor antagonist (5-HT3RA, such as ondansetron), dexamethasone, and aprepitant administered before chemotherapy to prevent acute nausea and vomiting and dexamethasone plus aprepitant or aprepitant alone can be used to prevent delayed nausea and vomiting
Cisplatin significantly decreased body weight in a time-dependent manner compared to normal control animals during the 24–72 h period (P < 0.001). ere was a trend towards mitigation of the reduction in body weight during the 48–72 h (P < 0.001) period after ondansetron administration compared with cisplatin-treated rats. e administration of cisplatin significantly reduced food intake compared to that in normal control group rats throughout the observation period (P < 0.001)
Summary
Chemotherapy-induced nausea and vomiting (CINV) is among the most debilitating and distressing events in cytotoxic chemotherapy [1]. e emetic response to chemotherapy is classified into acute phase (emesis occurring in the first 24 h after chemotherapy administration) and delayed phase (emesis occurring more than 24 h after chemotherapy administration) [2]. Chemotherapy-induced nausea and vomiting (CINV) is among the most debilitating and distressing events in cytotoxic chemotherapy [1]. Us, there is an urgent need for effective control of CINV. For the treatment of nausea and vomiting in patients receiving high-emetic chemotherapy (HEC), the European Society of Medical Oncology (ESMO) and the Multinational Association of Supportive Care in Cancer (MASCC) guidelines [4] recommend a combination of a 5-hydroxytryptamine type 3 receptor antagonist (5-HT3RA, such as ondansetron), dexamethasone, and aprepitant administered before chemotherapy to prevent acute nausea and vomiting and dexamethasone plus aprepitant or aprepitant alone can be used to prevent delayed nausea and vomiting. Despite the availability of effective antiemetic drugs, control of CINV is suboptimal [5]. There is an unmet need for safer and less expensive antiemetic drugs
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