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1.
Chem Biol Interact ; 393: 110957, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38513929

RESUMO

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.


Assuntos
Doença de Huntington , Fármacos Neuroprotetores , Receptores Nicotínicos , Animais , Ratos , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Doença de Huntington/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , NF-kappa B/metabolismo , Nitrocompostos/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Propionatos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Nicotínicos/metabolismo , Transdução de Sinais , Tropizetrona/uso terapêutico
2.
Support Care Cancer ; 31(12): 640, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37851143

RESUMO

PURPOSE: There are no well-recognized guidelines for antiemesis during concurrent chemoradiotherapy (CCRT) for cervical cancer (CC) and nasopharyngeal cancer (NPC) until now. The study was designed to assess the efficacy and safety of fosaprepitant combined with tropisetron and dexamethasone in preventing nausea and vomiting during 5 weeks of fractionated radiotherapy and concomitant weekly low-dose cisplatin chemotherapy in patients with CC or NPC. METHODS: Patients with CC or NPC were scheduled to receive fractionated radiotherapy and weekly cisplatin (25-40 mg/m2) chemotherapy for at least 5 weeks. Patients stratified by tumor type and induction chemotherapy were 1:1 randomly assigned to receive fosaprepitant, tropisetron, and dexamethasone or tropisetron plus dexamethasone as an antiemetic regimen. Efficacy was assessed primarily by the cumulative incidence of emesis after 5 weeks of treatment, and safety by adverse events (AEs). RESULTS: Between July 2020 and July 2022, 116 patients consented to the study of whom 103 were included in this interim analysis (fosaprepitant group [N = 52] vs control group [N = 51]). The cumulative incidence of emesis at 5 weeks (competing risk analysis) was 25% (95% CI 14.2-37.4) for the fosaprepitant group compared with 59% (95% CI 43.9-71.0) for the control group. There was a significantly lower cumulative risk of emesis in the fosaprepitant group (HR 0.35 [95% CI 0.19-0.64]; p < 0.001). Fosaprepitant was well tolerated as the incidences of adverse events in the two groups were comparable. CONCLUSION: The addition of fosaprepitant to tropisetron plus dexamethasone significantly reduced the risk of nausea and vomiting during 5 weeks of CCRT in patients with CC or NPC, and fosaprepitant was well tolerated. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov on October 3, 2022, number NCT05564286.


Assuntos
Antieméticos , Antineoplásicos , Neoplasias Nasofaríngeas , Neoplasias do Colo do Útero , Feminino , Humanos , Cisplatino , Tropizetrona/uso terapêutico , Dexametasona , Antineoplásicos/efeitos adversos , Vômito/induzido quimicamente , Vômito/prevenção & controle , Estudos Prospectivos , Náusea/etiologia , Náusea/prevenção & controle , Náusea/tratamento farmacológico , Antieméticos/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Fracionamento da Dose de Radiação , Quimioterapia Combinada
4.
Cell Stress Chaperones ; 27(5): 513-521, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35972643

RESUMO

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.


Assuntos
Diabetes Mellitus Experimental , Neuropatias Diabéticas , Animais , Anti-Inflamatórios/uso terapêutico , Apoptose , Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/patologia , Inflamação/tratamento farmacológico , Interleucina-1/efeitos adversos , Ratos , Estreptozocina/efeitos adversos , Tropizetrona/uso terapêutico , Fator de Necrose Tumoral alfa , Proteína X Associada a bcl-2
5.
Ann Hematol ; 101(8): 1835-1841, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35668198

RESUMO

Chemotherapy-induced nausea and vomiting (CINV) is common in patients with lymphoma and multiple myeloma (MM) receiving high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT). Despite a standard triple antiemetic regimen of a neurokinin-1 (NK1) receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone is recommended, how to control the protracted CINV in ASCT setting remains an intractable problem. Here, we retrospectively analyze CINV data of 100 patients who received either SEAM (semustine, etoposide, cytarabine, melphalan) or MEL140-200 (high-dose melphalan) before ASCT, evaluate the efficacy and safety of multiple-day administration of fosaprepitant combined with tropisetron and olanzapine (FTO), and compare the results to those of patients who received a standard regimen of aprepitant, tropisetron, and dexamethasone (ATD). The overall rate of complete response (CR), defined as no emesis and no rescue therapy, is 70% in the FTO group compared to 36% in the ATD group. Although CR rates are comparable in the acute phase between the two groups, significantly more patients treated by FTO achieve CR in the delayed phase than those treated by ATD (74% vs. 38%, p < 0.001). Moreover, FTO treatment significantly reduced the percentage of patients who are unable to eat, as well as the requirement for rescue medications. Both regimens are well tolerated and most adverse events (AEs) were generally mild and transient. In conclusion, the antiemetic strategy containing multiple-day administration of fosaprepitant is safe and effective for preventing CINV in lymphoma and MM patients, particularly in the delayed phase.


Assuntos
Antieméticos , Antineoplásicos , Transplante de Células-Tronco Hematopoéticas , Linfoma , Mieloma Múltiplo , Olanzapina , Condicionamento Pré-Transplante , Tropizetrona , Antieméticos/uso terapêutico , Antineoplásicos/uso terapêutico , Dexametasona , Humanos , Linfoma/tratamento farmacológico , Melfalan , Morfolinas/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Náusea/induzido quimicamente , Náusea/prevenção & controle , Olanzapina/uso terapêutico , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo , Tropizetrona/uso terapêutico , Vômito/induzido quimicamente , Vômito/prevenção & controle
6.
Support Care Cancer ; 30(7): 6225-6232, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35449368

RESUMO

OBJECTIVE: A prospective randomized controlled trial was conducted to compare 5 mg olanzapine plus standard triple antiemetic therapy for the prevention of nausea and vomiting induced by multiple-day cisplatin chemotherapy. METHODS: Patients who received a 3-day cisplatin-based chemotherapy (25 mg/m2/d) were given either 5 mg olanzapine plus triple therapy with aprepitant, tropisetron, and dexamethasone (quadruple group) or 5 mg olanzapine plus tropisetron and dexamethasone, omitting aprepitant (triplet group). The primary endpoint was the complete response (CR) in the overall phase (OP) (0-120 h) between quadruple group and triplet group. The secondary endpoints were the CR in the acute phase (AP) (0-24 h) and delayed phase (DP) (25-120 h) between two groups. The first time of vomiting was also compared by Kaplan-Meier curves. The impact of chemotherapy-induced nausea and vomiting (CINV) on the quality of life was assessed by the Functional Living Index-Emesis (FLIE). Aprepitant-related adverse effects (AEs) were also recorded. RESULTS: (1) The primary endpoint CR during OP was 76.0% (45/59) vs 67.0% (41/61) between the quadruple group and triplet group (P = 0.271). The secondary endpoint CR during the AP was significantly higher in the quadruple group than in the triplet group, which was 100.0% (59/59) vs 93.0% (57/61) (P = 0.045). The difference of CR during delayed phase between the groups was especially higher in the quadruple group compared to the triplet group (76.0% (45/59) vs 67.0% (41/61) (P = 0.271)). The rate of patients who achieved total protection in the overall phase was also higher in the quadruple group than the triplet group (28.8% (17/59) vs 23.0% (14/61) (P = 0.463)). During the OP, the incidence of no vomiting in the quadruple group and the triplet group was 93.2% (55/59) vs 80.3% (49/61) (P = 0.038), respectively. (2) Kaplan-Meier curves of time to first emesis were obviously longer in the quadruple group compared with the triplet group (P = 0.031). According to FLIE, no impact of CINV on daily life was defined as total score of questionnaire > 108; this study exhibited identical life quality between two groups. (3) The most common aprepitant- or olanzapine-related AEs included sedation, fatigue, and constipation. The occurrences between two groups were identical. CONCLUSION: It may been recommended that 5 mg olanzapine plus tropisetron and dexamethasone, omitting aprepitant triplet regimen as an alternative therapy in prevention CINV induced by multiple-day cisplatin chemotherapy due to the excellent CINV control rate and safety.


Assuntos
Antieméticos , Antineoplásicos , Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Aprepitanto/uso terapêutico , Cisplatino/efeitos adversos , Dexametasona/uso terapêutico , Humanos , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Náusea/prevenção & controle , Olanzapina/uso terapêutico , Estudos Prospectivos , Qualidade de Vida , Tropizetrona/uso terapêutico , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Vômito/prevenção & controle
7.
Drug Res (Stuttg) ; 72(5): 268-273, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35426093

RESUMO

Minocycline, widely used as an antibiotic, has recently been found to have an anti-inflammatory, neuroprotective and anticonvulsant effects. This study was aimed to investigate the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole (PTZ)-induced seizures considering the possible involvement of 5-HT3 receptor in this effect. For this purpose, seizures were induced by intravenous PTZ infusion. All drugs were administrated by intraperitoneal (i.p.) route before PTZ injection. Also, 1-(m-chlorophenyl)-biguanide (mCPBG, a 5-HT3 receptor agonist) and Tropisetron (a 5-HT3 receptor antagonist) were used 45 minutes before minocycline treatment. Our results demonstrate that acute minocycline treatment (80 and 120 mg/kg) increased the seizure threshold. In addition, the 5-HT3 antagonist, tropisetron, at doses that had no effect on seizure threshold, augmented the anticonvulsant effect of minocycline (40 mg/kg), while mCPBG (0.2 mg/kg) blunted the anticonvulsant effect of minocycline (80 mg/kg). In conclusion, our findings revealed that the anticonvulsant effect of minocycline is mediated, at least in part, by inhibition of 5-HT3 receptor.


Assuntos
Anticonvulsivantes , Pentilenotetrazol , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Camundongos , Minociclina/efeitos adversos , Pentilenotetrazol/toxicidade , Receptores 5-HT3 de Serotonina/uso terapêutico , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Serotonina , Tropizetrona/uso terapêutico
8.
Complement Med Res ; 28(6): 516-522, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33784688

RESUMO

OBJECTIVE: We evaluated the efficacy of electroacupuncture combined with tropisetron in treating carboprost tromethamine-induced nausea and vomiting during cesarean section under lumbar anesthesia. METHODS: A total of 264 patients aged 22-40 years were enrolled, who received carboprost tromethamine and suffered nausea and vomiting during cesarean section under lumbar anesthesia. The patients were divided randomly into the control group, electroacupuncture group, tropisetron group, and electroacupuncture + tropisetron group. RESULTS: Compared to the control group, the nausea and vomiting scores decreased at T3 in both the electroacupuncture and electroacupuncture + tropisetron groups, and decreased at T4 in the electroacupuncture group, tropisetron group, and electroacupuncture + tropisetron group; the motilin, gastrin, and 5-hydroxytryptamine (5-HT) levels decreased at T5 in the other 3 groups. Compared to the electroacupuncture + tropisetron group, the nausea and vomiting scores increased at T3 in the control and tropisetron groups, and increased at T4 in the other 3 groups; the motilin, gastrin, and 5-HT levels increased at T5. CONCLUSIONS: Our study suggested that electroacupuncture combined with tropisetron could effectively relieve carboprost tromethamine-induced nausea and vomiting during cesarean section under lumbar anesthesia. The effect was better than its single application, and the reduced 5-HT, motilin, and gastrin levels might be involved in the underlying mechanism.


Assuntos
Antieméticos , Eletroacupuntura , Antieméticos/uso terapêutico , Carboprosta , Cesárea , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Indóis/uso terapêutico , Náusea/tratamento farmacológico , Náusea/terapia , Gravidez , Trometamina , Tropizetrona/uso terapêutico , Vômito/tratamento farmacológico , Vômito/terapia
9.
Chem Biol Interact ; 335: 109332, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33387473

RESUMO

Renal fibrosis is a major cause of renal failure in diabetic nephropathy. Tropisetron is an antagonist of the 5HT3 receptor that exhibits anti-fibrosis effects. The present research aimed to investigate the protected role of tropisetron against renal fibrosis of diabetic nephropathy and its molecular mechanisms. For this purpose, male Wistar rats were allocated into 5 groups of control, tropisetron, diabetes, tropisetron + diabetes, and glibenclamide + diabetes (n = 7). After induction of type 1 diabetes with a single injection of STZ, tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) were given to the rats daily by intraperitoneal injection for 2 weeks. The obtained data revealed that the treatment of diabetic rats with tropisetron led to a significant decrease in the elevated blood glucose, serum cystatin c, and urinary total protein (UTP) level, indicating the improvement of the impaired kidney function. Moreover, the results of Masson's trichrome staining showed that fibrosis attenuated in the kidney of diabetic rats after tropisetron treatment. RT-PCR and Western blotting revealed that TGF-ß1, the apoptotic mediator, and p53 were considerably declined in the kidney of diabetic rats in response to tropisetron treatment. Meanwhile, the expressions of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) were increased. These notable effects were equipotent with glibenclamide, as a standard drug, suggesting that tropisetron can alleviate renal fibrosis in diabetic nephropathy. Our data indicate that tropisetron could improve kidney function and attenuate renal fibrosis through regulation of TGF-ß1, p53, and expression of extracellular matrix metalloproteinases.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Fibrose/tratamento farmacológico , Rim/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Tropizetrona/uso terapêutico , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/patologia , Fibrose/patologia , Fibrose/prevenção & controle , Glucose/metabolismo , Rim/patologia , Masculino , Proteínas/metabolismo , Ratos Wistar , Estreptozocina
10.
Cell Stress Chaperones ; 26(1): 217-227, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33047279

RESUMO

Tropisetron is a 5-HT3 receptor antagonist that exerts protective effect against DN. The aim of this study was to investigate the possible molecular mechanisms associated with the renoprotective effects of tropisetron in STZ-induced diabetic rats. Animals were subdivided into 5 equal groups; control, tropisetron, diabetes, tropisetron + diabetes, and glibenclamide + diabetes (n = 7). For induction of type 1 diabetes, a single injection of STZ (55 mg/kg, i.p.) was administered to the animals. Diabetic rats were treated with tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) for 2 weeks. According to the conducted analysis, diabetes led to renal dysfunction (reduction in glomerular filtration rate and urine urea and creatinine as well as elevation in plasma urea and creatinine) and abnormalities in antioxidant defense system (reduction in TAC and elevation in MDA), compared with the control group, which was prevented by tropisetron treatment. Reverse transcription-quantitative polymerase chain reaction and western blotting analysis demonstrated that SIRT1 gene expression decreased while FOXO3a and NF-κB gene expression as well as phosphorylated FOXO3a/total FOXO3a protein ratios and claudin-1 protein level increased in the kidney of diabetic rats compared with the control group. Herein, the results of this research showed that tropisetron treatment reversed these changes. Besides, all these changes were comparable with those produced by glibenclamide as a positive control. Hence, tropisetron ameliorated renal damage due to diabetic nephropathy possibly by suppressing oxidative stress and alteration of SIRT1, FOXO3a, and claudin-1 levels.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Tropizetrona/uso terapêutico , Animais , Claudina-1/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Proteína Forkhead Box O3/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Ratos , Ratos Wistar , Sirtuína 1/metabolismo
11.
JAMA Netw Open ; 3(10): e2013443, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33052400

RESUMO

Importance: Postoperative delirium is a frequent disorder for patients undergoing surgery and is associated with poor outcomes. Delirium may occur in the immediate period after anesthesia administration and surgery. Tropisetron, which is frequently administrated for postoperative nausea and vomiting, is also a partial agonist of α7 nicotinic acetylcholine receptors associated with neuroprotective effects. Tropisetron may be the potential pharmacological treatment to decrease delirium after noncardiac surgery. Objective: To perform a randomized clinical trial to determine the efficacy and safety of tropisetron for prevention of emergence delirium in patients undergoing noncardiac surgery. Design, Setting, and Participants: This single-center, 2-arm randomized, double-blind, placebo-controlled trial will include 1508 patients undergoing noncardiac surgery. The intervention group will receive 5 mg of intravenous tropisetron before anesthesia induction, and patients in the control group will receive a placebo. The primary end point is the incidence of emergence delirium within 1 hour after tracheal tube removal, measured by the Confusion Assessment Method for the Intensive Care Unit score. The main secondary outcome is the incidence of postoperative delirium measured at 3 days of follow-up. An intention-to-treat principle will be used for all analyses. Discussion: Delirium remains the most common neuropsychiatric complication for patients after surgery. This will be the first randomized clinical study to evaluate whether tropisetron is effective in preventing emergence delirium. Results from this study will provide evidence for alteration of daily practice. Trial Registration: ClinicalTrials.gov Identifier: NCT04027751.


Assuntos
Anestesia/efeitos adversos , Delírio do Despertar/induzido quimicamente , Delírio do Despertar/prevenção & controle , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/tratamento farmacológico , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Tropizetrona/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Neurochem Res ; 45(11): 2631-2640, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32797381

RESUMO

Tropisetron and Granisetorn are 5-HT3 antagonists with antiemetic effects. Tropisetron also has a partial agonistic effect on alpha-7 nicotinic acetylcholine receptors (α7 nAChRs). On the other hand, chronic cerebral hypoperfusion (CCH) attenuates cerebral blood flow and impairs cognitive functions. The goal of this study was to investigate the effect of Tropisetron and Granisetron on CCH-induced spatial memory impairment in rats. Forty-eight male Wistar rats were used in this study. 2-VO surgery was done to induce CCH and Radial Eight Arm Maz apparatus was used to evaluate spatial memory (working and reference memory). Tropisetron was injected intraperitoneally at the doses of 1 and 5 mg/kg, and Granisetron was injected intraperitoneally at the dose of 3 mg/kg. Dorsal hippocampal (CA1) neurons count, Interleukin 6 (IL-6) serum level, and serotonin-reuptake transporter (SERT) gene expression were also evaluated. The results showed, CCH impaired working and reference memory, increased IL-6 serum level, and decreased CA1 neurons and SERT expression. Tropisetron at the dose of 5 mg/kg restored all the effects of CCH. However, Granisetron did not restore CCH-induced memory impairment. Furthermore, Granisetron had no effect on IL-6. While, it increased SERT expression and CA1 neurons. In conclusion, Tropisetron but not Granisetron, ameliorated spatial memory impairment induced by CCH. We suggested conducting more detailed studies investigating the role of serotonergic system (5-HT3 receptors and serotonin transporters) and also α7 nAChRs in the effects of Tropisetron.


Assuntos
Granisetron/uso terapêutico , Transtornos da Memória/tratamento farmacológico , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Memória Espacial/efeitos dos fármacos , Tropizetrona/uso terapêutico , Animais , Arteriopatias Oclusivas/complicações , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Artéria Carótida Primitiva/cirurgia , Transtornos Cerebrovasculares/complicações , Interleucina-6/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/etiologia , Neurônios/efeitos dos fármacos , Proteínas de Ligação a RNA/metabolismo , Ratos Wistar
13.
Int Immunopharmacol ; 79: 106158, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31926479

RESUMO

Confident relationships between diabetes andliver damagehave previously been established. This study was designed to evaluate hepaticinflammation, apoptosis, and endocannabinoid system alterations in diabetes with or withouttropisetrontreatment. Rats were assigned to five equal groups: control, tropisetron, diabetes, tropisetron+diabetes, and glibenclamide+diabetes (n = 7 in each group). Rats were treated with tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) as a positive control for two weeks after type 1 diabetes induction.Inflammatory cytokines tumor necrosis factor-alpha and interleukin 6 (TNF-α and IL-6) levels, apoptotic cells, and fatty acid amide hydrolase (FAAH) enzyme, at both transcriptional and protein levels increased, while the gene expression of cannabinoid receptor 1 (CB1) and its protein level decreased in the diabetic liver compared to the control. Treatment with tropisetron reversed TNF-α, apoptotic index, and endocannabinoid system components. These effects were equipotent with glibenclamide, indicating that tropisetroncan protect liver tissue against diabetic disturbances. These findings strongly support the idea that diabetes-induced liver abnormality is mediated by inflammatory reactions, apoptosis, and endocannabinoid system, and that these effects can be alleviated by using tropisetron as an antioxidant and anti-inflammatory agent.


Assuntos
Complicações do Diabetes/tratamento farmacológico , Endocanabinoides/metabolismo , Hepatite/tratamento farmacológico , Inflamação/tratamento farmacológico , Fígado/metabolismo , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Tropizetrona/uso terapêutico , Amidoidrolases/genética , Amidoidrolases/metabolismo , Animais , Apoptose , Humanos , Interleucina-6/metabolismo , Fígado/patologia , Masculino , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
14.
Chin Clin Oncol ; 9(2): 17, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31865713

RESUMO

Review the clinical evidence of tropisetron or palonosetron, an old- and new-generation serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor antagonist (RA), respectively, for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer, and evaluate any difference in efficacy trends. A literature search of the EMBASE and PubMed databases was performed to identify publications of intravenous (IV) tropisetron (generic forms or Navoban®) for the treatment of CINV in patients with various cancers. Data from the pivotal clinical studies evaluating the IV formulation of Aloxi® (palonosetron HCl) were also considered. The effectiveness and safety of each antiemetic was summarized. Sixteen papers for tropisetron fulfilled the inclusion criteria and were extracted for full analysis; publications from six pivotal palonosetron clinical trials were considered. No direct data comparisons could be made between the two drugs, due to the varying definitions of efficacy endpoints between studies. For tropisetron, the rates of no emesis were lower in patients receiving highly emetogenic chemotherapy (HEC) versus moderately emetogenic chemotherapy (MEC). For palonosetron, the rates of complete response (no emesis, no rescue medication) were comparable in the MEC and HEC settings, demonstrating the effectiveness of this agent in patients receiving HEC. Both antiemetics offered some protection against nausea, although lower rates of no nausea were achieved compared with rates of no emesis. Two trials that evaluated the efficacy of palonosetron and tropisetron within the same study reported that palonosetron was more effective than tropisetron in controlling delayed vomiting in the HEC and MEC settings, with significantly higher rates of no emesis observed (P≤0.01). Palonosetron was non-inferior or more efficacious in controlling CINV compared with other older 5-HT3RAs, such as dolasetron, ondansetron, and granisetron. Conversely, tropisetron was no more efficacious than ondansetron or granisetron. Both tropisetron and palonosetron were generally well tolerated, with adverse event profiles consistent with drugs of this class (e.g., headache, constipation, and diarrhea). These data suggest that palonosetron is a highly selective prophylactic agent that may have an improved therapeutic profile compared with tropisetron, and is a feasible treatment option for controlling CINV in patients with cancer.


Assuntos
Antineoplásicos/efeitos adversos , Náusea/tratamento farmacológico , Neoplasias/complicações , Palonossetrom/uso terapêutico , Tropizetrona/uso terapêutico , Vômito/tratamento farmacológico , Feminino , Humanos , Masculino , Náusea/induzido quimicamente , Palonossetrom/farmacologia , Tropizetrona/farmacologia , Vômito/induzido quimicamente
16.
Biomed Pharmacother ; 110: 380-388, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30529771

RESUMO

OBJECTIVE: The objective of the present investigation was to explore the possible effect of the 5-HT3 receptor antagonist tropisetron on the expression levels of the inflammatory factors interleukin 6 (IL-6), creatine kinase isoenzyme (CK-MB), soluble growth stimulating gene 2 protein (sST2) and immunoglobulin E (IgE), as well as the cardiac action potential in septic rats. METHODS: The cecal ligation and perforation (CLP) method was utilized to construct abdominal infarction in rats. A total of 68 male adult Sprague Dawley rats were used, including 40 for assessing survival and 28 for detecting the expression levels of IL-6 and IgE, myocardial injury, cardiac dysfunction and the cardiac action potential. These 28 rats were divided into the sham (6 rats), sham + Tropisetron (6 rats), CLP (8 rats) and CLP + Tropisetron (8 rats) groups. Twenty-four hours after establishment of the sepsis rat model, immunohistochemistry was used to analyze 5-HT3 receptor protein expression, and enzyme-linked immunosorbent assay (ELISA) was employed to monitor the serum levels of IL-6, CKMB, sST2 and IgE. Furthermore, the structure of the myocardium in various groups was examined by H&E staining. RESULTS: The levels of IL-6, CK-MB, sST2 and IgE in the sepsis group were significantly higher than those of the sham group (P < 0.01). Furthermore, the heart rate in the sepsis group was lower than that of the sham group (P < 0.01), and the time of atrial ventricular action potential in the sepsis group was longer than that of the sham group (P < 0.05). In addition, immunohistochemical analyses showed that the area, intensity and index of 5-HT3 receptor in the sepsis group were significantly lower than those of the sham group (P < 0.01). Importantly, the 5-HT3 receptor antagonist Tropisetron exhibited significant inhibitory effects IL-6, CK-MB, sST2 and IgE expression levels, and inductive effects on atrial ventricular action potential in the sepsis group. CONCLUSIONS: Sepsis leads to systemic inflammatory reaction, resulting in myocardial injury, structural changes and immune imbalance. The inhibitory effect of tropisetron on inflammation, and the regulatory inflammatory disorder by the efferent vagus nerve may be one of the important mechanisms leading to cardiac electrophysiological changes in sepsis.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Coração/efeitos dos fármacos , Mediadores da Inflamação/antagonistas & inibidores , Sepse/tratamento farmacológico , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Tropizetrona/uso terapêutico , Potenciais de Ação/fisiologia , Animais , Modelos Animais de Doenças , Coração/fisiologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Preparação de Coração Isolado/métodos , Masculino , Ratos , Ratos Sprague-Dawley , Sepse/metabolismo , Antagonistas do Receptor 5-HT3 de Serotonina/farmacologia , Tropizetrona/farmacologia
17.
Medicine (Baltimore) ; 97(50): e13698, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30558082

RESUMO

Tropisetron is an adjuvant for dezocine used in intravenous patient-controlled analgesia (PCA) and has been reported to provide superior pain control. It is efficacious in reducing the institutional incidence of postoperative nausea and vomiting (PONV), which decreases resource utilization and cost. However, no scientific evidence has been reported in the literature demonstrating analytical confirmation of the compatibility and stability of the combination of dezocine and tropisetron. Thus, the present study aimed to investigate the stability of dezocine with tropisetron in 0.9% sodium chloride injection form for PCA administration.Commercial solutions of dezocine and tropisetron were combined and examined for compatibility and stability when diluted with 0.9% sodium chloride injection in polyolefin bags and glass bottles stored at 4°C or 25°C for up to 14 days. The initial concentrations were 40 mg/100 mL dezocine and 5 mg/100 mL tropisetron. For all samples, the compatibility parameters (including precipitation, cloudiness, discoloration, and pH values) were evaluated. Chemical stability was also determined using high-performance liquid chromatographic (HPLC) analysis.After a 14-day period of storage at 4°C or 25°C, the initial concentrations of dezocine and tropisetron were maintained at at least 98%. All of the mixtures remained clear and colorless throughout the observation period, and no color change or precipitation was observed.These results indicated that admixtures of 40 mg/100 mL dezocine and 5 mg/100 mL tropisetron in 0.9% sodium chloride injection were stable for at least 14 days when stored in polyolefin bags or glass bottles at 4°C or 25°C and protected from light.


Assuntos
Analgesia Controlada pelo Paciente/métodos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Tetra-Hidronaftalenos/uso terapêutico , Tropizetrona/uso terapêutico , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/química , Analgésicos Opioides/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/química , Cromatografia Líquida/métodos , Combinação de Medicamentos , Estabilidade de Medicamentos , Humanos , Injeções/métodos , Farmacopeias como Assunto , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Náusea e Vômito Pós-Operatórios/prevenção & controle , Antagonistas do Receptor 5-HT3 de Serotonina/administração & dosagem , Antagonistas do Receptor 5-HT3 de Serotonina/química , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Cloreto de Sódio , Tetra-Hidronaftalenos/administração & dosagem , Tetra-Hidronaftalenos/química , Tropizetrona/administração & dosagem , Tropizetrona/química
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