[Fire dragon cupping in prevention and treatment of chemotherapy-induced nausea and vomiting in breast cancer: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy and safety of fire dragon cupping in prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in breast cancer. METHODS: Sixty breast cancer patients receiving medium-high emetogenic chemotherapy regimen were randomly divided into an observation group (30 cases, 3 cases dropped out) and a control group (30 cases, 3 cases dropped out). In both groups, 5 mg tropisetron hydrochloride was given intravenously on the day of chemotherapy and 1st to 3rd days after chemotherapy. In the observation group, fire dragon cupping on the abdomen was applied on 1st, 3rd and 5th days after chemotherapy. The incidence of nausea, vomiting, loss of appetite, abdominal pain, abdominal distension, the severity of nausea, vomiting on 1st to 6th days after chemotherapy, and the duration of nausea, vomiting, loss of appetite were observed in the two groups. The self-rating anxiety scale (SAS) score, general comfort questionnaire scale (GCQ) score before and after treatment and remedy antiemetic medication were observed in the two groups, and the safety was evaluated. RESULTS: On 2nd to 6th days after chemotherapy, the number of patients with nausea, loss of appetite and abdominal distension and nausea scores in the observation group were lower than those in the control group (P<0.05). On 1st to 3rd days after chemotherapy, the number of patients with vomiting and vomiting scores in the observation group were lower than those in the control group (P<0.05). The duration of nausea, vomiting and loss of appetite in the observation group were shorter than those in the control group (P<0.05). In the observation group, there was no significant difference in SAS and GCQ scores before and after treatment (P>0.05). After treatment, the GCQ score in the control group was decreased compared with that before treatment (P<0.05). After treatment, there was no significant difference in SAS and GCQ scores between the two groups (P>0.05). There was no significant difference in the number of patients using remedy medication between the two groups (P>0.05). No adverse reaction occurred during treatment in both groups. CONCLUSION: Fire dragon cupping can effectively reduce the incidence of nausea, vomiting, loss of appetite and the severity of nausea, vomiting related to chemotherapy in breast cancer, and improve patient comfort, and have good safety.

[Heat-sensitive moxibustion combined with tropisetron hydrochloride for chemotherapy-induced nausea and vomiting: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy of heat-sensitive moxibustion combined with tropisetron hydrochloride and tropisetron hydrochloride alone in the treatment of chemotherapy-induced nausea and vomiting (CINV). METHODS: Sixty CINV patients were randomly divided into an observation group and a control group, 30 cases in each group.The control group was treated with tropisetron hydrochloride. On the basis of the treatment in the control group, heat-sensitive acupoints were explored at Zhongwan (CV 12), Shenque (CV 8), Qihai (CV 6), Guanyuan (CV 4), Shangwan (CV 13), Xiawan (CV 10), Jianli (CV 11) and bilateral Zusanli (ST 36), Neiguan (PC 6), Tianshu (ST 25), Liangmen (ST 21) areas in the observation group，and heat-sensitive moxibustion was applied at heat-sensitive acupoints. The treatment started from the day of chemotherapy in both groups, once a day for 7 days. The occurrence and severity of nausea and vomiting after chemotherapy were recorded after each treatment on the 1st to 7th days of chemotherapy in the two groups, the complete remission rate was evaluated. The KPS score, quality of life scale score before and after treatment and incidence of myelosuppression were compared between the two groups. RESULTS: On the 2nd to 4th days of chemotherapy, the incidence and severity of nausea and vomiting in the observation group were lower than those in the control group (P<0.05), the complete remission rates of nausea and vomiting were higher than those in the control group (P<0.05). After treatment, the KPS score in the observation group was higher than those before treatment and in the control group (P<0.05). After treatment, the scores of emotional function and overall health status in the observation group were higher than those before treatment and in the control group (P<0.05), the scores of fatigue, pain, insomnia, loss of appetite and diarrhea were lower than those before treatment and in the control group (P<0.05). The incidence of myelosuppression in the observation group was 20.0% (6/30), which was lower than 46.7% (14/30) in the control group (P<0.05). CONCLUSION: Heat-sensitive moxibustion combined with tropisetron hydrochloride can effectively reduce nausea and vomiting after chemotherapy in patients with malignant tumor, improve the quality of life, relieve the myelosuppression caused by chemotherapy drugs.

Evaluation of the effect of intraoperative tropisetron on postoperative rebound pain after brachial plexus block: a randomized controlled trial.

Introduction: Postoperative rebound pain after peripheral nerve block increases patient suffering and delays recovery after surgery. Objectives: We tested whether the 5HT-3 receptor antagonist and α7nAChR agonist tropisetron could prevent postoperative rebound pain. Methods: A total of 115 patients were randomized to receive 5-mg/5-mL tropisetron or the same volume of normal saline. Pain intensity was measured with the numerical rating scale of pain (NRS). Rebound pain was defined as a change from mild pain (NRS ≤ 3) measured in the postanesthesia care unit to severe pain (NRS ≥ 7) within 24 hours after peripheral nerve blockade. Logistic regression was used to identify relevant factors associated with postoperative rebound pain. Results: Tropisetron did not affect the NRS score or the incidence of rebound pain after peripheral nerve block. Logistic regression revealed that preoperative pain, bone surgery, and length of incision were risk factors for postoperative rebound pain, and patient-controlled analgesia was protective against postoperative rebound pain. Conclusion: Tropisetron does not affect the incidence of rebound pain after peripheral nerve block. Patients at high risk of postoperative rebound pain should be identified for appropriate management. Registration site: www.chictr.org.cn (ChiCTR2300069994).

5-HT3 antagonist, tropisetron, ameliorates age-related renal injury induced by D-galactose in male mice: Up-regulation of sirtuin 1.

Objectives: The kidney ages faster than other organs due to changes in energy metabolism, mitochondrial dysfunction, and oxidative stress. This study looked into the anti-aging effect of tropisetron. Materials and Methods: D-galactose was administrated subcutaneously in a mouse model for eight weeks in order to induce renal aging. Three separate intraperitoneal doses of tropisetron (1, 3, and 5 mg/kg body weight) were given at the same time. We assessed markers of mitochondrial dysfunction, oxidative stress, and inflammation. Via Real-Time PCR, the expressions of genes linked to aging (SIRT1) and apoptosis (Bax and Bcl-2) were ascertained. In addition, an assessment of histopathological changes, blood urea nitrogen, and creatinine concentrations was done. Results: In kidney tissue, tropisetron reduces mitochondrial dysfunction and oxidative stress, which are caused by D-galactose-induced overproduction of inflammatory mediators. Additionally, tropisetron demonstrated antiapoptotic activity in renal tissue and augmented the decrease in SIRT1 gene expression associated with D-galactose administration. Besides, tropisetron significantly improved the histological alterations in the renal tissues of aged mice and effectively decreased the elevated levels of creatinine and also blood urea nitrogen. Conclusion: The results provided additional insight into the effect of tropisetron on renal aging and the underlying mechanisms, particularly through its ability to modulate SIRT1 signaling.

Activation of alpha-7 nicotinic acetylcholine receptor by tropisetron mitigates 3-nitropropionic acid-induced Huntington's disease in rats: Role of PI3K/Akt and JAK2/NF-κB signaling pathways.

Huntington's disease (HD) is an inheritable autosomal-dominant disorder that targets mainly the striatum. 3-Nitropropionic acid (3-NP) induces obvious deleterious behavioral, neurochemical, and histological effects similar to the symptoms of HD. Our study aimed to examine the neuroprotective activity of tropisetron, an alpha-7 neuronal nicotinic acetylcholine receptor (α-7nAChR) agonist, against neurotoxic events associated with 3-NP-induced HD in rats. Forty-eight rats were randomly allocated into four groups. Group I received normal saline, while Groups II, III and IV received 3-NP for 2 weeks. In addition, Group III and IV were treated with tropisetron 1 h after 3-NP administration. Meanwhile, Group IV received methyllycaconitine (MLA), an α-7nAChR antagonist, 30 min before tropisetron administration. Treatment with tropisetron improved motor deficits as confirmed by the behavioral tests and restored normal histopathological features of the striatum. Moreover, tropisetron showed an anti-oxidant activity via increasing the activities of SDH and HO-1 as well as Nrf2 expression along with reducing MDA level. Tropisetron also markedly upregulated the protein expression of p-PI3K and p-Akt which in turn hampered JAK2/NF-κB inflammatory cascade. In addition, tropisetron showed an anti-apoptotic activity through boosting the expression of Bcl-2 and reducing Bax expression and caspase-3 level. Interestingly, all the aforementioned effects of tropisetron were blocked by pre-administration of MLA, which confirms that such neuroprotective effects are mediated via activating of α-7nAChR. In conclusion, tropisetron showed a neuroprotective activity against 3-NP-induced HD via activating PI3K/Akt signaling and suppressing JAK2/NF-κB inflammatory axis. Thus, repositioning of tropisetron could represent a promising therapeutic strategy in management of HD.

Tropisetron restores normal expression of BAD, SIRT1, SIRT3, and SIRT7 in the rat pressure overload-induced cardiac hypertrophy model.

Tropisetron exerts a protective effect against cardiac complications, particularly cardiac hypertrophy. Oxidative stress and apoptosis are the main contributors to the pathogenesis of cardiac hypertrophy. Sirtuins, a family of histone deacetylases, are connected to cellular oxidative stress signaling and antioxidant defense. Sirtuins are also linked to apoptosis which is an important mechanism in the progression of cardiac hypertrophy to heart failure. Literature also suggests that tropisetron impedes apoptosis, partly mediated through an antioxidant mechanism. Therefore, we examined if tropisetron fights cardiac hypertrophy by adjusting sirtuin family proteins (Sirts) and components of mitochondrial death pathway, Bcl-associated X (BAX), Bcl-2-associated death promoter (BAD). Male Sprague-Dawley rats got divided into four groups, including control (Ctl), tropisetron (Trop), cardiac hypertrophy (Hyp), and hypertrophic rats under tropisetron treatment (Hyp + Trop). Pathological cardiac hypertrophy was induced by surgical abdominal aortic constriction (AAC). The increased expression of brain natriuretic peptide (BNP) in the Hyp group confirms the cardiac hypertrophy establishment. The mRNA levels of SIRT1, SIRT3, SIRT7, and BAD also upregulated in the hypertrophic group (p < 0.001). Postoperational administration of tropisetron for 3 weeks lowered the increased expression of BNP (p < 0.05) and BAD (p < 0.001), though the reduction of BAX expression was statistically insignificant (p > 0.05). Tropisetron treatment also restored the normal level of SIRT1/3/7 genes expression in the Hyp + Trop group (p < 0.05). Present findings suggest that tropisetron can suppress cardiomyocyte hypertrophy progression to heart failure by counteracting BNP, SIRT1, SIRT3, Sirt7, and BAD overexpression-mediated apoptosis in a rat model of cardiac hypertrophy.

Inhibiting 5-hydroxytryptamine receptor 3 alleviates pathological changes of a mouse model of Alzheimer's disease.

Extracellular amyloid beta (Aß) plaques are main pathological feature of Alzheimer's disease. However, the specific type of neurons that produce Aß peptides in the initial stage of Alzheimer's disease are unknown. In this study, we found that 5-hydroxytryptamin receptor 3A subunit (HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice (an Alzheimer's disease model) and patients with Alzheimer's disease. To investigate whether HTR3A-positive interneurons are associated with the production of Aß plaques, we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aß plaques in the mouse model. Some amyloid precursor protein-positive or ß-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aß plaques were co-localized with HTR3A interneurons. These results suggest that HTR3A -positive interneurons may partially contribute to the generation of Aß peptides. We treated 5.0-5.5-month-old model mice with tropisetron, a HTR3 antagonist, for 8 consecutive weeks. We found that the cognitive deficit of mice was partially reversed, Aß plaques and neuroinflammation were remarkably reduced, the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice. These findings suggest that HTR3A interneurons partly contribute to generation of Aß peptide at the initial stage of Alzheimer's disease and inhibiting HTR3 partly reverses the pathological changes of Alzheimer's disease.

Tropisetron Ameliorated Cyclophosphamide-Induced Hemorrhagic Cystitis via Restraining TLR-4/NF-κB and JAK1/STAT3 Signaling Pathways.

OBJECTIVE: The main pathological changes of hemorrhagic cystitis (HC) are bladder inflammation, bladder epithelial damage and mast cell infiltration. Tropisetron has been corroborate to conduct a protective role in HC, but its specific etiology remains unclear. The objective of this research was to estimate the mechanism of action of Tropisetron in haemorrhagic cystitis tissue. METHODS: Cyclophosphamide (CTX) was utilized to induce the construction of HC rat model, and rats were handled with different doses of Tropisetron. The impact of Tropisetron on the expression of inflammatory factors and oxidative stress factors in the rats with cystitis were measured by western blot, as well as the related proteins of toll-like receptor 4/nuclear transcription factor-κB (TLR-4/NF-κB) and januskinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways. RESULTS: CTX-induced cystitis in rats was accompanied by notable pathological tissue damage and increased bladder wet weight ratio, elevated mast cell numbers and collagen fibrosis compared to controls. Tropisetron ameliorated CTX-induced injury in a concentration-dependent manner. Futhermore, CTX induced oxidative stress and inflammatory damage, while Tropisetron can alleviate these injuries. Besides, Tropisetron ameliorated CTX-induced cystitis by restraining TLR-4/NF-κB and JAK1/STAT3 signalling pathways. CONCLUSIONS: Taken together, Tropisetron ameliorates cyclophosphamide-induced haemorrhagic cystitis via modulating TLR-4/NF-κB and JAK1/STAT3 signalling pathways. These findings carry important implication for the study of the molecular mechanisms of pharmacological treatment of hemorrhagic cystitis.

Cardiovascular effects of bufotenin on human 5-HT4 serotonin receptors in cardiac preparations of transgenic mice and in human atrial preparations.

It is unclear whether bufotenin (= N,N-dimethyl-serotonin = 5-hydroxy-N,N-dimethyl-tryptamine), a hallucinogenic drug, can act on human cardiac serotonin 5-HT4 receptors. Therefore, the aim of the study was to examine the cardiac effects of bufotenin and for comparison tryptamine in transgenic mice that only express the human 5-HT4 receptor in cardiomyocytes (5-HT4-TG), in their wild-type littermates (WT) and in isolated electrically driven (1 Hz) human atrial preparations. In 5-HT4-TG, we found that both bufotenin and tryptamine enhanced the force of contraction in left atrial preparations (pD2 = 6.77 or 5.5, respectively) and the beating rate in spontaneously beating right atrial preparations (pD2 = 7.04 or 5.86, respectively). Bufotenin (1 µM) increased left ventricular force of contraction and beating rate in Langendorff perfused hearts from 5-HT4-TG, whereas it was inactive in hearts from WT animals, as was tryptamine. The positive inotropic and chronotropic effects of bufotenin and tryptamine were potentiated by an inhibitor of monoamine oxidases (50 µM pargyline). Furthermore, bufotenin concentration- (0.1-10 µM) and time-dependently elevated force of contraction in isolated electrically stimulated musculi pectinati from the human atrium and these effects were likewise reversed by tropisetron (10 µM). We found that bufotenin (10 µM) increased the phosphorylation state of phospholamban in the isolated perfused hearts, left and right atrial muscle strips of 5-HT4-TG but not from WT and in isolated human right atrial preparations. In summary, we showed that bufotenin can increase the force of contraction via stimulation of human 5-HT4 receptors transgenic mouse cardiac preparations but notably also in human atrial preparations.

Tropisetron Ameliorated Cyclophosphamide-Induced Hemorrhagic Cystitis via Restraining TLR-4/NF-kB and JAK1/STAT3 Signaling Pathways

Objective: The main pathological changes of hemorrhagic cystitis (HC) are bladder inflammation, bladder epithelial damage and mast cell infiltration. Tropisetron has been corroborate to conduct a protective role in HC, but its specific etiology remains unclear. The objective of this research was to estimate the mechanism of action of Tropisetron in haemorrhagic cystitis tissue. Methods: Cyclophosphamide (CTX) was utilized to induce the construction of HC rat model, and rats were handled with different doses of Tropisetron. The impact of Tropisetron on the expression of inflammatory factors and oxidative stress factors in the rats with cystitis were measured by western blot, as well as the related proteins of toll-like receptor 4/nuclear transcription factor-κB (TLR-4/NF-κB) and januskinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways. Results: CTX-induced cystitis in rats was accompanied by notable pathological tissue damage and increased bladder wet weight ratio, elevated mast cell numbers and collagen fibrosis compared to controls. Tropisetron ameliorated CTX-induced injury in a concentration-dependent manner. Futhermore, CTX induced oxidative stress and inflammatory damage, while Tropisetron can alleviate these injuries. Besides, Tropisetron ameliorated CTX-induced cystitis by restraining TLR-4/NF-κB and JAK1/STAT3 signalling pathways. Conclusions: Taken together, Tropisetron ameliorates cyclophosphamide-induced haemorrhagic cystitis via modulating TLR-4/NF-κB and JAK1/STAT3 signalling pathways. These findings carry important implication for the study of the molecular mechanisms of pharmacological treatment of hemorrhagic cystitis (AU)

Tropisetron improved testicular inflammation in the streptozotocin-induced diabetic rats: The role of toll-like receptor 4 (TLR4) and mir146a.

As a serotonin antagonist, tropisetron positively affects blood glucose lowering, insulin synthesis, pancreas inflammation, and apoptosis in diabetes. Reproductive disorders are one of the diabetes-induced chronic complications. The present study aimed to evaluate the effect of tropisetron on diabetes-induced testicular inflammation, its signaling pathway, and mir146a. To this end, animals were assigned to the control, tropisetron, diabetes (DM), DM-tropisetron, and DM-glibenclamide groups. Streptozotocin (50 mg/kg) was intraperitoneally injected to provide diabetes. Tropisetron and glibenclamide were then administrated intraperitoneally for 2 weeks after diabetes induction. Testes histology, real-time polymerase chain reaction, western blot analysis, ELISA, and immunohistochemistry assays were also performed. The finding revealed that tropisetron significantly improved diabetes-induced testis damages, lowered TLR4, TRAF6, IRAK1, NF-κB, and caspase3 protein expressions, and decreased TNF-α and IL-1 levels. Moreover, the mir146a expression declined following the tropisetron treatment. This study demonstrated that the significant role of tropisetron in lowering testicular inflammation and apoptosis might have been due to the inhibition of the TLR4/IRAK1/TRAF6 signaling pathway and thereby the attenuation of NF-κB and caspase3 expression and inflammatory cytokines. Furthermore, the downregulation of mir146a, as an inflammatory microRNA interacting with TLR4, showed another pathway, through which tropisetron improved diabetes-induced testicular injuries.

Prevention of postoperative nausea and vomiting after gynaecological day surgery under remimazolam general anesthesia: a randomized double-blind controlled study.

PURPOSE: To observe the effect of different antiemetic drugs for the prevention of postoperative nausea and vomiting (PONV) after gynaecological day surgery under remimazolam general anesthesia. METHODS: One hundred ninety-two patients were selected for gynaecological day surgery and randomly divided into three groups: droperidol group (DD group), tropisetron group (DT group) and control group (DC group). Flurbiprofen axetil 50 mg and dexamethasone 5 mg were given intravenously before induction of anesthesia, and 2 min later droperidol 1 mg was given intravenously to the DD group, tropisetron 5 mg to the DT group and saline (5 ml) to the DC group. Induction of anesthesia: remimazolam 6 mg/kg/h was continuously infused until sleep, mivacurium 0.2 mg/kg and alfentanil 20ug/kg were slowly pushed, 3 min later intubation was performed to control breathing. Maintenance of anesthesia: 40ug/kg/h of alfentanil, 1 mg/kg/h of remimazolam continuous infusion. After awakening and extubation, the patient was transferred to the PACU. PONV were recorded in the PACU and an electronic questionnaire was pushed 24 h after surgery. RESULTS: The incidence of PONV within the PACU was significantly lower in the DD (14.5%)and DT(26.7%) groups than in the DC(50%) group (p < 0.01), there was no significantly difference between the DT and DD groups. There were no significant difference in the incidence of PONV in 24 h after surgery between the three groups(DD:DT:DC = 44.5%:45.1%:63.8%,p > 0.05). CONCLUSIONS: Droperidol or tropisetron combined with dexamethasone is superior to dexamethasone alone for the prevention of PONV in the PACU after remimazolam combined with alfentanil anesthesia, with no significant difference in the incidence of PONV in 24 h after surgery.

The effect of tropisetron on peripheral diabetic neuropathy: possible protective actions against inflammation and apoptosis.

Diabetic peripheral neuropathy (DPN) is a common nerve disorder of diabetes. The aim of this study was to explore the protective effects of tropisetron in DPN. Type 1 diabetes was created by a single injection of streptozotocin (50 mg/kg, ip). Tropisetron (3 mg/kg, ip) was administered daily for 2 weeks. Our analysis showed that nerve fibers and their myelin sheaths were thinned with decreased myelinated fiber number in diabetic animals. The intensity of Bcl-2 staining decreased and the intensity of Bax staining increased in the sciatic nerves of diabetic rats by using immunohistochemical staining. Furthermore, diabetes significantly increased tumor necrosis factor-alpha, interleukin 1-ß (TNFα and IL-1ß) and Bax/Bcl-2 ratio in sciatic nerves of rats. However, intraperitoneal injection of tropisetron significantly reversed these alterations induced by diabetes. These findings suggest that tropisetron attenuates diabetes-induced peripheral nerve injury through its anti-inflammatory and anti-apoptotic effects, and may provide a novel therapeutic strategy to ameliorate the process of peripheral neuropathy in diabetes.

Tropisetron Preconditioning Decreases Myocardial Biomarkers in Patients Undergoing Heart Valve Replacement Surgery.

Background: Cardioplegic arrest during the heart valve replacement surgery frequently leads to myocardial damage. Tropisetron (TRP) has been demonstrated to reduce myocardial ischemia-reperfusion injury and inflammation in animals. We examined the efficacy of TRP in lowering myocardial biomarkers in patients undergoing heart valve replacement surgery. Methods: A total of seventy-five patients, scheduled for elective heart valve replacement surgery, were randomly chosen to receive either 10 ml of normal saline or 10 mg/10 ml of TRP immediately after anesthesia induction. Blood samples for the measurement of cardiac troponin I (cTnI), creatine kinase (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-10 (IL-10) were taken before anesthesia, as well as 4, 12, and 24 h after aortic cross-clamp release to evaluate myocardial injury using two-way ANOVA for repeated measurements. The study was registered at www.chictr.org.cn (number, ChiCTR-1800018681). Results: Treatment with TRP decreased the increment of cTnI (Fgroup = 4.911, p = 0.030; Ftime = 55.356, p = 0.001; Fgroup × time = 5.340, p = 0.002) at 12 and 24 h; of CK-MB (Fgroup = 6.552, p = 0.013; Ftime = 49.276, p = 0.001; Fgroup × time = 7.627, p = 0.003) at 4, 12, and 24 h; of TNF-α (Fgroup = 4.153, p = 0.046; Ftime = 28.244, p = 0.002; Fgroup × time = 4.692, p = 0.006) at 4 and 12 h; and of LDH (Fgroup = 4.275, p = 0.043; Ftime = 63.225, p = 0.001; Fgroup × time = 2.501, p = 0.083) at 24 h after the release of the aortic cross-clamp. It increased IL-10 (Fgroup = 5.958, p = 0.018; Ftime = 31.226, p = 0.002; Fgroup × time = 1.464, p = 0.236) at 12 h after the release of the aortic cross-clamp. Multiple linear regression analysis showed that cardiopulmonary bypass (CPB) time was a risk factor, and that TRP treatment was a protective factor for postoperative cTNI change (ß = 4.449, 95% CI [0.97-7.92], p = 0.013 for CPB time; and ß = -381, 95% CI [-613.4 to -148.5], p = 0.002 for TRP treatment). Conclusions: Tropisetron had cardioprotective and anti-inflammatory effects in patients undergoing heart valve replacement surgery with cardioplegic arrest. The addition of TRP and reduction of CPB time should be considered for myocardial protection in heart valve replacement surgery. Clinical Trial Registration: [www.chictr.org.cn/index.aspx], identifier [ChiCTR1800018681].

Tropisetron attenuates neuroinflammation and chronic neuropathic pain via α7nAChR activation in the spinal cord in rats.

OBJECTIVES: Tropisetron is an alpha 7 nicotinic acetylcholine receptor (α7nAChR) agonist and is a commonly used antiemetic clinically. α7nAChRs activation modulating nociception transmissions and cholinergic anti-inflammation may decrease neuropathic pain. This study was set to investigate the effects of tropisetron on neuropathic pain and neuroinflammation as well as the underlying mechanisms in rats. METHODS: Neuropathic pain behavior was assessed in rats using the paw mechanical withdrawal threshold and paw thermal withdrawal latency before and after the establishment of a spared nerve injury (SNI) pain model in rats treated with tropisetron treatment in the presence or absence of the α7nAChR antagonist methyllycaconitine (MLA) through intrathecal injection. Their spinal cords were then harvested for inflammatory cytokines, the α7nAChR, p38 mitogen-activated protein kinase (p-p38MAPK) and cAMP-response element binding protein (CREB) measurement. RESULTS: Tropisetron effectively alleviated mechanical allodynia and thermal hyperalgesia; decreased IL-6, IL-1ß and TNF-a; and down-regulated the phosphorylation of p38MAPK and CREB. Pre-treatment with MLA abolished these effects of tropisetron. CONCLUSION: Our data indicate that tropisetron alleviates neuropathic pain may through inhibition of the p38MAPK-CREB pathway via α7nAChR activation. Thus, tropisetron may be a potential new therapeutic strategy for chronic neuropathic pain.

Synthesis and Development of Indole Based 5-HT3 Receptor Antagonists as Anti-Emetic Drugs in Oncology: An Update.

An important group of antiemetic drugs used in the treatment of nausea and vomiting after chemotherapy containing an indole moiety in their structures, working as 5- hydroxytryptamine type 3 serotonin receptor antagonist (5-HT3). This study focuses on compounds bearing an indole core that present a 5-HT3 receptor antagonist activity, which have been successfully used as antiemetic drugs for reducing chemotherapy adverse secondary effects during cancer treatment. Their synthesis, biological activities, and some outstanding characteristics are discussed, providing a general outlook towards the development of more efficient antiemetic drugs.

Comparison of ondansetron and tropisetron in preventing postoperative nausea and vomiting: A meta-analysis of randomized controlled trials.

OBJECTIVES: To compare the efficacy of prophylactic ondansetron and tropisetron for postoperative nausea and vomiting (PONV). METHODS: A literature search was performed to identify studies that compare the efficiency of ondansetron with that of tropisetron in preventing PONV. Only randomized controlled trials updated to January, 2021 were included. RESULTS: The final pooled analysis included 14 studies totaling 1705 patients and indicated that ondansetron was 39% less effective than tropisetron in preventing postoperative vomiting with a higher incidence of dizziness. However, no significant difference was detected between ondansetron and tropisetron in PONV, postoperative nausea, antiemetic treatment, and headache. CONCLUSIONS: Tropisetron is superior to ondansetron in preventing postoperative vomiting.PROSPERO No: CRD42021237368.

In vitro effects of tropisetron and granisetron against Echinococcus granulosus (s.s.) protoscoleces by involvement of calcineurin and calmodulin.

BACKGROUND: Cystic echinococcosis (CE) is a disease caused by the larval stage of Echinococcus granulosus sensu lato  (s.l.). The treatment of CE mainly relies on the use of benzimidazoles, which can commonly cause adverse side effects. Therefore, more efficient treatment options are needed. Drug repurposing is a useful approach for advancing drug development. We have evaluated the in vitro protoscolicidal effects of tropisetron and granisetron in E. granulosus sensu stricto (s.s.) and assessed the expression of the calcineurin (CaN) and calmodulin (CaM) genes, both of which have been linked to cellular signaling activities and thus are potentially promising targets for the development of drugs. METHODS: Protoscoleces (PSC) of E. granulosus (s.s.) (genotype G1) obtained from sheep hepatic hydatid cysts were exposed to tropisetron and granisetron at concentrations of 50, 150 and 250 µM for various periods of time up to 10 days. Cyclosporine A (CsA) and albendazole sulfoxide were used for comparison. Changes in the morphology of PSC were investigated by light microscopy and scanning electron microscopy. Gene expression was assessed using real-time PCR at the mRNA level for E. granulosus calcineurin subunit A (Eg-CaN-A), calcineurin subunit B (Eg-CaN-B) and calmodulin (Eg-CaM) after a 24-h exposure at 50 and 250 µM, respectively. RESULTS: At 150 and 250 µM, tropisetron had the highest protoscolicidal effect, whereas CsA was most effective at 50 µM. Granisetron, however, was less effective than tropisetron at all three concentrations. Examination of morphological alterations revealed that the rate at which PSC were killed increased with increasing rate of PSC evagination, as observed in PSC exposed to tropisetron. Gene expression analysis revealed that tropisetron at 50 µM significantly upregulated Eg-CaN-B and Eg-CaM expression while at 250 µM it significantly downregulated both Eg-CaN-B and Eg-CaM expressions; in comparison, granisetron decreased the expression of all three genes at both concentrations. CONCLUSIONS: Tropisetron exhibited a higher efficacy than granisetron against E. granulosus (s.s.) PSC, which is probably due to the different mechanisms of action of the two drugs. The concentration-dependent effect of tropisetron on calcineurin gene expression might reflect its dual functions, which should stimulate future research into its mechanism of action and evaluation of its potential therapeutical effect in the treatment of CE.

[Application of Methylprednisolone Sodium Succinate Combined with Tropisetron in Prevention of Nausea and Vomiting under Microvascular Decompression of Hemifacial Spasm].

Objective To evaluate the effect of methylprednisolone sodium succinate combined with tropisetron on postoperative nausea and vomiting(PONV)under microvascular decompression of hemifacial spasm.Methods From January to June 2019,485 patients undergoing microvascular decompression for facial spasm at Department of Neurosurgery,Peking University People's Hospital were randomly assigned into two groups with random number table method.For group A(n=242),2 ml saline was administrated by intravenous drip before induction and 5 mg tropisetron after operation.For group B(n=243),40 mg methylprednisolone sodium succinate was administrated by intravenous drip before induction and 5 mg tropisetron after operation.The anesthesia time,operation time,and incidence of PONV in 0-24 h and 24-48 h were recorded for the comparison of the remedial treatment rate of nausea and vomiting between the two groups.Results There was no significant difference in age,gender,smoking history,body mass index value,American Society of Anesthesiologists score,medical history,surgical side,PONV history,operation time or anesthesia time between the two groups(all P > 0.05).The incidence of PONV in group A was 35.5% and 18.2% during 0-24 h and 24-48 h,respectively,which was significantly higher than that(18.5%,χ 2=7.331,P=0.007;8.2%,χ 2=4.364,P=0.037)in group B.The application rate of antiemetic drugs in group A was 15.2% and 8.7% during 0-24 h and 24-48 h,respectively,which was significantly higher than that(5.3%,χ 2=5.327,P=0.021;2.0%,χ 2=4.432,P=0.035)in group B.Conclusion The combination of methylprednisolone sodium succinate and tropisetron can effectively prevent PONV under microvascular decompression of hemifacial spasm,with the performance superior to single drug treatment.

Tropisetron balances immune responses via TLR2, TLR4 and JAK2/STAT3 signalling pathway in LPS-stimulated PBMCs.

Numerous documents have been stated that tropisetron, an antagonist of the 5-HT3 receptor and α7nAChR agonist, modulates immune responses. However, the mechanistic basis for this aspect of tropisetron action is largely unknown. Here, the immuno-modulatory effects of tropisetron are investigated, focusing on the possible molecular targets and the mechanisms. Aside from the well-characterized role in immune signalling, JAK2/STAT3, TLR2 and TLR4 are signal transducers linked to both immuno-modulatory actions of acetylcholine and serotonin. Therefore, we evaluated their involvement in the immunoregulatory effects of tropisetron. To test the hypothesis, we assessed the expression of pro-/anti-inflammatory cytokines including TNF-α, IL-1ß, IL-17 and IL-10 following tropisetron treatment in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) derived from healthy subjects. Tropisetron up-regulates the transcription of TLR2, TLR4, JAK2 and STAT3 genes. Tropisetron also increases the expression of target pro-inflammatory cytokines, although considerably suppresses the pro-inflammatory cytokines (IL-1ß, IL-17 and TNF-α) levels in media. Tropisetron notably promotes both IL-10 gene expression and secretion. These findings confirm the antiphlogistic properties of tropisetron. The present data also shed light on a new aspect of tropisetron immune-modulatory action that engaged TLR2, TLR4 and JAK2/STAT3 signalling cascades.