ABSTRACT
AIM: To investigate the inhibitory impact of chlorogenic acid (CGA) on the growth of Morganella psychrotolerans and its ability to form histamine. METHODS AND RESULTS: The antimicrobial effect of CGA on M. psychrotolerans was evaluated using the minimum inhibitory concentration (MIC) method, revealing an MIC value of 10 mg ml-1. The alkaline phosphatase (AKP) activity, cell membrane potential, and scanning electron microscopy images revealed that CGA treatment disrupted cell structure and cell membrane. Moreover, CGA treatment led to a dose-dependent decrease in crude histidine decarboxylase (HDC) activity and gene expression of histidine decarboxylase (hdc). Molecular docking analysis demonstrated that CGA interacted with HDC through hydrogen bonds. Furthermore, in situ investigation confirmed the efficacy of CGA in controlling the growth of M. psychrotolerans and significantly reducing histamine formation in raw tuna. CONCLUSION: CGA had good activity in controlling the growth of M. psychrotolerans and histamine formation.
Subject(s)
Chlorogenic Acid , Histamine , Histamine/analysis , Chlorogenic Acid/pharmacology , Histidine Decarboxylase/genetics , Histidine Decarboxylase/metabolism , Molecular Docking Simulation , SeafoodABSTRACT
Cisplatin (CDDP) is extensively utilized in the management of diverse types of cancers, but its ototoxicity cannot be ignored, and clinical interventions are not ideal. Histidine decarboxylase (HDC) is the exclusive enzyme for histamine synthesis. Anti-histamine receptor drugs are ubiquitously employed in the therapeutics of allergies and gastrointestinal diseases. Yet, the specific role of histamine and its signaling in the inner ear is not fully understood. This study utilized cisplatin treated mice and HEI-OC1 auditory hair cell line to establish a cisplatin-induced ototoxicity (CIO) model. Histidine decarboxylase knockout (HDC-/-) mice and histamine receptor 1 (H1R) antagonist were utilized to investigate the influence of HDC/histamine/H1R signaling on ototoxicity. The results identified HDC and H1R expression in mouse hair cells. Transcriptomics indicated that the expression levels of oxidative stress-related genes in the cochlea of HDC-/- mice increased. Furthermore, histamine deficiency or suppression of H1R signaling accelerated HC ferroptosis, a pivotal factor underlying the aggravation of CIO in vivo and in vitro, conversely, the supplementation of exogenous histamine reversed these deleterious effects. Mechanistically, this study revealed that the malfunction of HDC/histamine/H1R signaling induced upregulation of NRF2 expression, accompanied by the upregulation of ACSL4 and downregulation of GPX4 expression, which are major regulatory factors of ferroptosis. In summary, histamine deficiency may induce hair cell death by regulating the H1R pathway and exacerbate CIO. Our findings have indicated a potential therapeutic target for CIO.
Subject(s)
Cisplatin , Ferroptosis , Hair Cells, Auditory , Histamine , Histidine Decarboxylase , Mice, Knockout , Signal Transduction , Animals , Histidine Decarboxylase/genetics , Histidine Decarboxylase/metabolism , Histamine/metabolism , Hair Cells, Auditory/drug effects , Hair Cells, Auditory/pathology , Hair Cells, Auditory/metabolism , Mice , Ferroptosis/drug effects , Signal Transduction/drug effects , Ototoxicity , Receptors, Histamine H1/metabolism , Receptors, Histamine H1/genetics , Antineoplastic Agents/adverse effects , Mice, Inbred C57BL , Cell Line , Male , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/geneticsABSTRACT
Adenocarcinomas mamarios fueron inducidos en ratas Sprague-Dawley mediante N-nitraso-N-metil-urea (NMV). Una vez que el primer tumor se hacía evidente, los animales fueron tratados diariamente con una dosis oral de 4 mg/kg de animal de Levamisol (Leva). La actividad de histidina decarboxilasa (HDC), expresada dpm/(g,h), se determinó en el tumor y en el intestino con C-histidina por medición de actividad de CO2 con espectrometría de centelleo líquido. La histopatología demostró que todos los tumores inducidos eran adenocarcinomas mamarios más o menos diferenciados. Como fuera observado en otros casos, la actividad de HDC tumoral fue alta comparada con la de tejidos normales. El tratamiento con Leva durante 7 y 14 días no produjo influencias significativas sobre la actividad de HDC, si bien se evidenció una disminución de la actividad enzimática. La administración de Leva durante más de 20 días provocó una disminución significativa de la actividad de HDC. La actividad de dicha enzima dependió, en todos los casos, de la masa total del tumor (MTT). La actividad de HDC en función de MTT es una función lineal con coeficientes de correlación superiores a 0,9. Para las ratas tratadas con Leva durante 20 días o más, la pedndiente fue de 1,93 ñ 0,89. Para animales no tratados, la pendiente fue de 7,37 ñ 1,23. La diferencia es estadisticamente significativa de acuerdo al criterio de la distribución F (P <0,001). Nuestros resultados demuestran que un agente inmunomodulador exhibe un definido tiempo de retraso antes de ejercer su influencia sobre el metbolismo de la histamina, el cual anormal en diferentes tipos de tumores. En trabajos futuros se estudiará si este efecto está relacionado con la acción inmunomoduladora de la droga