RESUMEN
BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is very common worldwide, and alcohol consumption is a notable contributing factor. Researches have shown that gut microbiota can be influenced by alcohol consumption and is an important mediator in regulating Th17 cell immunity. However, it is still unclear the exact mechanism by which alcohol exacerbates the CP/CPPS and the role of gut microbiota in this process. METHOD: We first constructed the most-commonly used animal model for CP/CPPS, the experimental autoimmune prostatitis (EAP) model, through immunoassay. Based on this, mice were divided into EAP group and alcohol-consuming EAP group. By 16S rRNA sequencing and non-targeted metabolomics analysis, differential gut microbiota and their metabolites between the two groups were identified. Subsequently, metabolomics detection targeting cholesterols was carried out to identify the exact difference in cholesterol. Furthermore, multiple methods such as flow cytometry and immunohistochemistry were used to detect the differentiation status of Th17 cells and severity of prostatitis treated with 27-hydroxycholesterol (the differential cholesterol) and its upstream regulatory factor-sterol regulatory element-binding protein 2 (SREBP2). Lastly, fecal transplantation was conducted to preliminary study on whether alcohol intake exacerbates EAP in immune receptor mice. RESULTS: Alcohol intake increased the proportion of Th17 cells and levels of related inflammatory factors. It also led to an altered gut bacterial richness and increased gut permeability. Further metabolomic analysis showed that there were significant differences in a variety of metabolites between EAP and alcohol-fed EAP mice. Metabolic pathway enrichment analysis showed that the pathways related to cholesterol synthesis and metabolism were significantly enriched, which was subsequently confirmed by detecting the expression of metabolic enzymes. By targeting cholesterol synthesis, 27-hydroxycholesterol was significantly increased in alcohol-fed EAP mice. Subsequent mechanistic research showed that supplementation with 27-hydroxycholesterol could aggravate EAP and promote Th17 cell differentiation both in vivo and in vitro, which is regulated by SREBP2. In addition, we observed that fecal transplantation from mice with alcohol intake aggravated EAP in immunized recipient mice fed a normal diet. CONCLUSION: Our study is the first to show that alcohol intake promotes Th17 cell differentiation and exacerbates EAP through microbiota-derived cholesterol biosynthesis.
Asunto(s)
Consumo de Bebidas Alcohólicas , Enfermedades Autoinmunes , Diferenciación Celular , Colesterol , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Prostatitis , Células Th17 , Animales , Masculino , Células Th17/inmunología , Prostatitis/inmunología , Prostatitis/microbiología , Prostatitis/metabolismo , Prostatitis/inducido químicamente , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/inmunología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/inducido químicamente , Ratones , Diferenciación Celular/efectos de los fármacos , Consumo de Bebidas Alcohólicas/efectos adversos , Colesterol/metabolismo , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genéticaRESUMEN
Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a common and serious disease with unclear pathogenesis and recurrent symptoms. Hedyotis diffusa Willd (HDW) has been recognized for its potential in managing various chronic inflammatory diseases. This research aimed to interrogate the mechanism of HDW in treating CP/CPPS. Complete Freund Adjuvant (CFA) and LPS were utilized to establish the rat and cell models of CP/CPPS. Results showed that HDW decreased levels of inflammation-related factors in CP rat prostate tissue and LPS-elicited RWPE-1 cell injury model. Moreover, HDW administration impaired oxidative stress in the prostate and RWPE-1 cells. In addition, HDW treatment activated the NRF2/ARE signaling in rat prostate tissue and cell models. Interestingly, NRF2/ARE pathway inhibitor ML385 reversed the inhibition effects of cell apoptosis, inflammation, and oxidative stress triggered by HDW. In summary, HDW alleviated inflammation and oxidative stress by activating NRF2/ARE signaling in CP/CPPS rat model and human prostate epithelial cell injury model.
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Hedyotis , Inflamación , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Prostatitis , Transducción de Señal , Masculino , Prostatitis/inducido químicamente , Prostatitis/patología , Prostatitis/metabolismo , Prostatitis/tratamiento farmacológico , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Humanos , Hedyotis/química , Ratas , Ratas Sprague-Dawley , Extractos Vegetales/farmacología , Próstata/efectos de los fármacos , Próstata/patología , Próstata/metabolismo , Línea Celular , Elementos de Respuesta Antioxidante/efectos de los fármacos , Enfermedad CrónicaRESUMEN
PURPOSE: Aimed to investigate the role of multiparametric magnetic resonance imaging (mp-MRI) in the diagnosis of granulomatous prostatitis caused by intravesical Bacillus Calmette-Guérin (BCG). METHODS: In this prospective, single-center study, 10 male patients who were given intravesical BCG due to intermediate- and high-risk bladder cancer were included. Before transurethral resection of bladder tumors (TURB), all patients were evaluated by mp-MRI, serum prostate-specific antigen (PSA), and digital rectal examination (DRE). Serum PSA levels and DRE findings were evaluated before and after intravesical BCG treatment. Prostate mp-MRI was performed for patients with elevated levels of serum PSA and/or with abnormal DRE findings. Then, MRI fusion + systematic prostate biopsy was performed. Demographic data of the patients before and after intravesical BCG were compared. RESULTS: The average age of the patients was 66.9 years (55-87 years). While PSA was 1.7 ng/ml before intravesical BCG treatment, it was 4.3 ng/ml after intravesical BCG treatment (p = 0.005). PSA density (PSAD) was 0.04 and 0.10 before and after the treatment, respectively (p = 0.012). DRE findings of all patients were normal before the treatment. However, abnormal findings were detected in 80% of them after the treatment (p = 0.008). PI-RADS ≥ 3 lesions were found to be significantly higher in all patients after intravesical BCG (p = 0.004). CONCLUSION: Granulomatous prostatitis is a rare complication of intravesical BCG. High PSA, abnormal DRE, and PI-RADS ≥ 3 lesions detected after intravesical BCG should suggest granulomatous prostatitis and unnecessary biopsies may be avoided.
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Vacuna BCG , Granuloma , Imágenes de Resonancia Magnética Multiparamétrica , Prostatitis , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Administración Intravesical , Vacuna BCG/efectos adversos , Diagnóstico Diferencial , Tacto Rectal , Granuloma/inducido químicamente , Granuloma/diagnóstico por imagen , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Estudios Prospectivos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico por imagen , Prostatitis/inducido químicamente , Prostatitis/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/prevención & controlRESUMEN
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common inflammatory immune disease of the urogenital system. High glucose intake is considered to be a potential promoter of autoimmune diseases. However, the influence of high glucose intake on CP/CPPS is unknown. This research aimed to explore the influences of high glucose intake on experimental autoimmune prostatitis (EAP), a valid animal model of CP/CPPS, and the underlying mechanism. NOD mice received 20% glucose water or normal water treatment during EAP induction. EAP severity and Th17 cell responses were evaluated. Then, we explored the effects of an IL-17A neutralizing antibody, an inhibitor of TGF-ß, the reactive oxygen species (ROS) inhibitor NAC, and the mitochondrial ROS (mtROS) antioxidant MitoQ on glucose-fed EAP mice. The results demonstrated that high glucose intake aggravated EAP severity and promoted Th17 cell generation, which could be ameliorated by the neutralization of IL-17A. In vitro experiments showed that high dextrose concentrations promoted Th17 cell differentiation through mtROS-dependent TGF-ß activation. Treatment with TGF-ß blockade, NAC, or MitoQ suppressed Th17 cell generation both in vivo and in vitro, resulting in the amelioration of EAP manifestations caused by high glucose intake. This study revealed that high glucose intake exacerbates EAP through mtROS-dependent TGF-ß activation-mediated Th17 differentiation. Our results may provide insights into the molecular mechanisms underlying the detrimental effects of an environmental factor, such as high glucose intake, on CP/CPPS.
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Enfermedades Autoinmunes , Prostatitis , Masculino , Humanos , Ratones , Animales , Prostatitis/inducido químicamente , Prostatitis/tratamiento farmacológico , Especies Reactivas de Oxígeno , Interleucina-17 , Células Th17 , Ratones Endogámicos NOD , Diferenciación Celular , Factor de Crecimiento Transformador beta , Glucosa , Modelos Animales de EnfermedadRESUMEN
A low-energy shock wave (LESW) has therapeutic effects on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); however, its mechanism of action remains unclear. We explored the effects of LESW on the prostate and mitochondrial dynamics regulators in a rat model of carrageenan-induced prostatitis. The imbalance of mitochondrial dynamics regulators may affect the inflammatory process and molecules and contribute to CP/CPPS. Male Sprague-Dawley rats received intraprostatic 3% or 5% carrageenan injections. The 5% carrageenan group also received LESW treatment at 24 h, 7 days, and 8 days. Pain behavior was evaluated at baseline, 1 week, and 2 weeks after a saline or carrageenan injection. The bladder and the prostate were harvested for immunohistochemistry and quantitative reverse-transcription polymerase chain reaction analysis. Intraprostatic carrageenan injection induced inflammatory reaction in the prostate and the bladder, decreased the pain threshold, and resulted in the upregulation of Drp-1, MFN-2, NLRP3 (mitochondrial integrity markers), substance P, and CGRP-RCP, whose effects were maintained for 1-2 weeks. LESW treatment suppressed carrageenan-induced prostatic pain, inflammatory reaction, mitochondrial integrity markers, and expression of sensory molecules. These findings support a link between the anti-neuroinflammatory effects of LESW in CP/CPPS and the reversal of cellular perturbations caused by imbalances in mitochondrial dynamics in the prostate.
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Dolor Pélvico , Prostatitis , Terapia por Ultrasonido , Ondas Ultrasónicas , Animales , Humanos , Masculino , Ratas , Carragenina , Modelos Animales de Enfermedad , Inflamación/metabolismo , Dinámicas Mitocondriales , Dolor Pélvico/inducido químicamente , Dolor Pélvico/terapia , Prostatitis/inducido químicamente , Prostatitis/terapia , Ratas Sprague-DawleyRESUMEN
Neurogenic inflammation and central sensitization play a role in chronic prostatitis/chronic pelvic pain syndrome. We explore the molecular effects of low-intensity shock wave therapy (Li-ESWT) on central sensitization in a capsaicin-induced prostatitis rat model. Male Sprague-Dawley rats underwent intraprostatic capsaicin (10 mM, 0.1 cm3) injections. After injection, the prostate received Li-ESWT twice, one day apart. The L6 dorsal root ganglion (DRG)/spinal cord was harvested for histology and Western blotting on days 3 and 7. The brain blood oxygenation level-dependent (BOLD) functional images were evaluated using 9.4 T fMRI before the Li-ESWT and one day after. Intraprostatic capsaicin injection induced increased NGF-, BDNF-, and COX-2-positive neurons in the L6 DRG and increased COX-2, NGF, BDNF, receptor Trk-A, and TRPV1 protein expression in the L6 DRG and the dorsal horn of the L6 spinal cord, whose effects were significantly downregulated after Li-ESWT on the prostate. Intraprostatic capsaicin injection increased activity of BOLD fMRI responses in brain regions associated with pain-related responses, such as the caudate putamen, periaqueductal gray, and thalamus, whose BOLD signals were reduced after Li-ESWT. These findings suggest a potential mechanism of Li-ESWT on modulation of peripheral and central sensitization for treating CP/CPPS.
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Tratamiento con Ondas de Choque Extracorpóreas , Prostatitis , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Capsaicina , Ciclooxigenasa 2/metabolismo , Ganglios Espinales/metabolismo , Humanos , Imagen por Resonancia Magnética , Masculino , Factor de Crecimiento Nervioso/metabolismo , Prostatitis/inducido químicamente , Prostatitis/diagnóstico por imagen , Prostatitis/terapia , Ratas , Ratas Sprague-Dawley , Médula Espinal/metabolismoRESUMEN
OBJECTIVE: Chronic nonbacterial prostatitis (CNP) has remained one of the most prevalent urological diseases, particularly in older men. Dihydroartemisinin (DHA) has been identified as a semi-synthetic derivative of artemisinin that exhibits broad protective effects. However, the role of DHA in inhibiting CNP inflammation and prostatic epithelial cell proliferation remains largely unknown. MATERIALS AND METHODS: CNP animal model was induced by carrageenan in C57BL/6 mouse. Enzyme linked immunosorbent assay (ELISA), Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to examine inflammatory cytokines and proliferation genes expression. Immunofluorescence and immunochemistry staining were used to detect and E2F7 expression. Human prostatic epithelial cells (HPECs) and RWPE-1 was induced by lipopolysaccharide (LPS) to mimic CNP model in vitro. Cell proliferation was determined using MTS assay. RESULTS: DHA significantly alleviated the rough epithelium and inhibited multilamellar cell formation in the prostatic gland cavity and prostatic index induced by carrageenan. In addition, DHA decreased the expression of TNF-α and IL-6 inflammatory factors in prostatitis tissues and in LPS-induced epithelial cells. Upregulation of transcription factor E2F7, which expression was inhibited by DHA, was found in CNP tissues, human BPH tissues and LPS-induced epithelial cells inflammatory response. Mechanically, we found that depletion of E2F7 by shRNA inhibited epithelial cell proliferation and LPS-induced inflammation while DHA further enhance these effects. Furthermore, HIF1α was transcriptional regulated by E2F7 and involved in E2F7-inhibited CNP and cellular inflammatory response. Interestingly, we found that inhibition of HIF1α blocks E2F7-induced cell inflammatory response but does not obstruct E2F7-promoted cell growth. CONCLUSION: The results revealed that DHA inhibits the CNP and inflammation by blocking the E2F7/HIF1α pathway. Our findings provide new evidence for the mechanism of DHA and its key role in CNP, which may provide an alternative solution for the prevention and treatment of CNP.
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Prostatitis , Anciano , Animales , Artemisininas , Carragenina/efectos adversos , Factor de Transcripción E2F7 , Células Epiteliales/metabolismo , Humanos , Inflamación/metabolismo , Lipopolisacáridos , Masculino , Ratones , Ratones Endogámicos C57BL , Prostatitis/inducido químicamente , Prostatitis/tratamiento farmacológico , Prostatitis/genéticaRESUMEN
Ertapenem is a carbapenem antibiotic usually reserved for complicated infections. Drug-induced neurotoxicity is a rare adverse reaction associated with ertapenem, and may be directly related to its chemical structure. We report a case of a 64-year-old male with a hematological history and chronic prostatitis that was admitted to hospital for gait instability, clumsiness, dysarthria and tremors. He started ertapenem intravenous 1 g once daily a week prior to admission. Creatinine clearance calculation by the Cockcroft-Gault method was 52 mL/min and total protein levels were low. Ertapenem's administration was discontinued and the patient's neurological symptoms improved dramatically just one day after. The result of the Naranjo Scale was six, suggesting a probable adverse drug reaction. We discussed if he could receive meropenem in case of severe infection such as septic shock. Considering the patient's medical history, the chemical structure of meropenem and the fact that there are almost no reported cases of neurotoxicity from this drug, we assume that meropenem could be used in case of severe infection in patients with history of neurotoxicity caused by ertapenem if no added risk factors are present, such as renal failure.
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Encefalopatías , Síndromes de Neurotoxicidad , Prostatitis , Antibacterianos/farmacología , Encefalopatías/inducido químicamente , Encefalopatías/complicaciones , Encefalopatías/tratamiento farmacológico , Ertapenem/efectos adversos , Humanos , Masculino , Meropenem , Persona de Mediana Edad , Síndromes de Neurotoxicidad/tratamiento farmacológico , Síndromes de Neurotoxicidad/etiología , Prostatitis/inducido químicamente , Prostatitis/complicaciones , Prostatitis/tratamiento farmacológicoRESUMEN
OBJECTIVE: To categorize multiparametric MRI features of Bacillus Calmette-Guérin (BCG)-related granulomatous prostatitis (GP) and discover potential manifestations for its differential diagnosis from prostate cancer. MATERIALS AND METHODS: The cases of BCG-related GP in 24 male (mean age ± standard deviation, 66.0 ± 9.4 years; range, 50-88 years) pathologically confirmed between January 2011 and April 2019 were retrospectively reviewed. All patients underwent intravesical BCG therapy followed by a MRI scan. Additional follow-up MRI scans, including diffusion-weighted imaging (DWI), were performed in 19 patients. The BCG-related GP cases were categorized into three: A, B, or C. The lesions with diffusion restriction and homogeneous enhancement were classified as type A. The lesions with diffusion restriction and a poorly enhancing component were classified as type B. A low signal intensity on high b-value DWI (b = 1000 s/mm²) was considered characteristic of type C. Two radiologists independently interpreted the MRI scans before making a consensus about the types. RESULTS: The median lesion size was 22 mm with the interquartile range (IQR) of 18-26 mm as measured using the initial MRI scans. The lesion types were A, B, and C in 7, 15, and 2 patients, respectively. Cohen's kappa value for the inter-reader agreement for the interpretation of the lesion types was 0.837. On the last follow-up MRI scans of 19 patients, the size decreased (median, 5.8 mm; IQR, 3.4-8.5 mm), and the type changed from A or B to C in 11 patients. The lesions resolved in four patients. In five patients who underwent prostatectomy, caseous necrosis on histopathology matched with the non-enhancing components of type B lesions and the entire type C lesions. CONCLUSION: BCG-related GP demonstrated three imaging patterns on multiparametric MRI. Contrast-enhanced T1-weighted imaging and DWI may play a role in its differential diagnosis from prostate cancer.
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Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Prostatitis , Neoplasias de la Vejiga Urinaria , Anciano , Anciano de 80 o más Años , Vacuna BCG/efectos adversos , Imagen de Difusión por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/diagnóstico por imagen , Prostatitis/inducido químicamente , Prostatitis/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
Phytochemical study of the MeOH extract of Cucumis prophetarum fruits (family Cucurbitaceae) by using different chromatographic techniques led to the isolation of three metabolites; spinasterol (1), cucurbitacin B (2), and 2-O-ß-D-glucopyranosylcucurbitacin E (3). Their chemical structures were created on the basis of physical, chemical, spectroscopic data 1D (1H and 13C NMR), and 2D NMR (HSQC and HMBC), as well as similarity with literature data. Cucurbitacin B (Cu-B) (2) was found to be the major constituent. Potential protective activities of MeOH extract, CHCl3, and EtOAc fractions and Cu-B were evaluated against carrageenan-induced prostatic inflammation in rats. Acute toxicity was assessed by evaluating LD50. Pretreatment with CHCl3 fraction and Cu-B ameliorated the rise in the prostate index and obviously protected against histopathological changes. Further, MeOH, extract, CHCl3, and EtOAc fractions as well as Cu-B significantly protected against oxidative stress in prostatic tissues. The anti-inflammatory activities of the extract, fractions and Cu-B were confirmed by ameliorating the rise in prostatic content of the inflammatory mediators TNF-α, IL-1ß, COX-2, and iNOS induced by carrageenan. In addition, the rise in the chemotactic factors were myeloperoxidase (MPO), F4-80, and monocyte chemoattractant protein-1 (MCP-1) was significantly hampered. In conclusion, three known compounds (1-3) were isolated from Cucumis prophetarum fruits. Cu-B (2) was the major identified compound. Particularly, CHCl3 fraction and isolated Cu-B exhibited potent anti-inflammatory activity against carrageenan-induced prostatitis. The anti-inflammatory activity can be attributed, at least partly, to inhibition of neutrophil and macrophage infiltration into prostatic tissues.
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Cucumis , Prostatitis , Animales , Antiinflamatorios/farmacología , Carragenina/toxicidad , Humanos , Masculino , Fitoquímicos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Prostatitis/inducido químicamente , Prostatitis/tratamiento farmacológico , Prostatitis/prevención & control , RatasRESUMEN
BACKGROUND: Due to limited data on the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and the suboptimal therapeutic effect, the development of new and effective treatment modalities was needed urgently. Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been reported for the treatment of CP/CPPS. However, the underlying mechanism remains to be elucidated. OBJECTIVE: To interrogated the efficacy and the mechanism of Li-ESWT in the treatment of CP/CPPS. MATERIALS AND METHODS: According to different treatments, RWPE-1 cells (human prostate epithelial cells) were randomly divided into three groups: control group, LPS (lipopolysaccharide) group, or Li-ESWT group (LPS-induced RWPE-1 managed by Li-ESWT). Following the Li-ESWT treatment, the levels of oxidative stress were assayed. We then established a rat model of experimental autoimmune prostatitis (EAP) by injecting prostatic protein homogenate mixed with complete Freund's adjuvant. The Sprague-Dawley rats were randomly divided into the control group, EAP group, or Li-ESWT group. Von Frey Filament was used to quantify pelvic hyperalgesia in the rats. Prostates tissues from each group were collected for immunohistochemistry, oxidation stress, and Western blot analysis. RESULTS: Histological analysis showed reduced inflammation and expression of cytokines (TNF-α, IL-1ß, IL-6, COX-2, SP) in prostate tissues from the Li-ESWT group compared with those from the EAP group (all p < 0.05). Similarly, there was reduced pelvic pain and allergic symptoms in the Li-ESWT group compared with the EAP group (all p < 0.05). Besides, Li-ESWT treatment could decrease oxidative stress in the prostate and in RWPE-1 cells, respectively (both p < 0.05). Moreover, the Li-ESWT upregulated the expression of CAT through the inhibition of phosphorylation of AKT/FOXO1 signaling pathway. DISCUSSION AND CONCLUSIONS: Li-ESWT may reduce inflammation, oxidative stress, and pain in rats with autoimmunity-induced prostatitis via the PI3 K/AKT/FOXO1 pathway. It implies that Li-ESWT can present a potential therapeutic option for the treatment of CP/CPPS.
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Enfermedades Autoinmunes/terapia , Tratamiento con Ondas de Choque Extracorpóreas , Dolor Pélvico/terapia , Prostatitis/terapia , Transducción de Señal/genética , Animales , Enfermedades Autoinmunes/inducido químicamente , Modelos Animales de Enfermedad , Inflamación , Lipopolisacáridos , Masculino , Proteínas del Tejido Nervioso/metabolismo , Estrés Oxidativo , Dolor Pélvico/etiología , Dolor Pélvico/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Prostatitis/inducido químicamente , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Tadalafil (TAD) is primarily a treatment drug for erectile dysfunction. Studies have shown that TAD has a therapeutic effect on prostatitis, but the specific mechanism has not been reported. LPS induced RWPE-1 cells to form a model of chronic nonbacterial prostatitis (CNP). Cell activity was measured by MTT assay. Apoptosis was detected by TUNEL assay. Western blot was used to detect the expression of apoptosis-related proteins Bcl-2, Bax, Caspase-3, and cleaved caspase3. ELISA was used to detect the expression of inflammatory cytokines TNF-α, IL-6, and IL-8. GSH, catalase (CAT), and malondialdehyde (MDA) kits were used to detect the expression of oxidative stress-related indicators GSH, CAT, and MDA. Western blot was used to detect the expression of proteins related to Akt/Nrf2 signaling pathway. After different concentrations of TAD were given, the survival rate of LPS-induced RWPE-1 cells decreased, apoptosis increased, and inflammation and oxidative stress decreased. This process is accompanied by the activation of the Akt/Nrf2 signaling pathway. The addition of AKT inhibitor (HY-10249A) reversed the inhibitory effect of TAD on LPS-induced inflammatory response and oxidative stress of RWPE-1 cell. TAD alleviated LPS-induced inflammation and oxidative stress of RWPE-1 cell by regulating the Akt/Nrf2 signaling pathway.
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Antiinflamatorios/farmacología , Antioxidantes/farmacología , Mediadores de Inflamación/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Próstata/efectos de los fármacos , Prostatitis/prevención & control , Proteínas Proto-Oncogénicas c-akt/metabolismo , Tadalafilo/farmacología , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular , Proliferación Celular/efectos de los fármacos , Citocinas/metabolismo , Humanos , Lipopolisacáridos/toxicidad , Masculino , Próstata/enzimología , Próstata/patología , Prostatitis/inducido químicamente , Prostatitis/enzimología , Prostatitis/patología , Transducción de SeñalRESUMEN
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male urological disease characterized by chronic pelvic pain. Extracorporeal shock wave therapy (ESWT) has been used to treat patients with CP/CPPS, but the parameters used by ESWT are not uniformly determined. Herein, this study aims to assess the effects of ESWT with different energy flux densities on pelvic pain in CP/CPPS rats and to explore the mechanisms. A rat model of CP/CPPS was induced by intraprostatic injection of 1% carrageenan. ESWT with different energy flux densities (0.09, 0.20, 0.30, 0.40 mJ/mm2) was applied in the pelvic region of CP/CPPS rats once a week for 4 weeks. The results showed that compared with the other energy flux densities (0.09, 0.30, and 0.40 mJ/mm2), ESWT with 0.20 mJ/mm2 exhibited a more powerful effect in alleviating pelvic pain and prostate damage. The therapeutic effect is associated with the reduction of the number of total and degranulated mast cells. Collectively, ESWT with 0.20 mJ/mm2 achieved the optimal therapeutic effect in alleviating pelvic pain in CP/CPPS rats.
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Degranulación de la Célula , Tratamiento con Ondas de Choque Extracorpóreas , Mastocitos/metabolismo , Dolor Pélvico/metabolismo , Dolor Pélvico/terapia , Prostatitis/metabolismo , Prostatitis/terapia , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Masculino , Mastocitos/patología , Dolor Pélvico/inducido químicamente , Dolor Pélvico/patología , Prostatitis/inducido químicamente , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Dutasteride administration reportedly improves lower urinary tract symptoms in patient with chronic, histologically-identified prostatic inflammation, potentially through estrogen receptor ß (ERß), activation of which has anti-inflammatory effects in the prostate tissue. Therefore, we investigated the effect of dutasteride on intraprostatic inflammatory responses and bladder activity using a rat model of chemically induced prostatic inflammation. METHODS: Male Sprague-Dawley rats at 10 weeks old were used. Prostatic inflammation was induced by 5% formalin injection into ventral lobes of the prostate and saline was injected in the control group (control, n = 5). Rats with prostatic inflammation were divided into dutasteride therapy (dutasteride, n = 5) and placebo groups (placebo, n = 5). Dutasteride was administrated at a dose of 0.5 mg/kg daily from 2 days before induction of prostatic inflammation whereas placebo rats received vehicle only. Twenty-eight days later, cystometry was performed in a conscious condition to measure non-voiding contractions (NVCs), intercontraction intervals (ICI) and postvoid residual volume (RV). After cystometry, the prostate was excised for analysis of messenger RNA (mRNA) expression levels of ERα, ERß, interleukin-1ß (IL-1ß), and IL-18 by quantitative polymerase chain reaction. RESULTS: The mean number of NVCs was significantly greater in placebo group than that of control group without prostatic inflammation (p < .05), and ICI were significantly decreased in placebo group compared with control group (p < .05). On the contrary, there was no significant change in NVCs or ICI between control and dutasteride groups. RV was not significantly different among three groups. Gene expression levels of ERα, IL-1ß, and IL-18 was significantly increased in placebo rats compared with control rats (p < .05), but not significantly different between control and dutasteride rats. On the other hand, the mRNA expression level of ERß was significantly decreased in placebo rats (p < .05), but not in dutasteride rats, compared with control rats. CONCLUSION: Dutasteride treatment improved not only prostatic inflammation evident as increased gene expression levels in IL-1ß and IL-18, but also bladder overactivity shown by increased NVCs during bladder filling. These therapeutic effects were associated with the restored expression of anti-inflammatory ERß. Therefore, dutasteride might be effective via ERß modulation for the treatment of prostatic inflammation in addition to its previously known, anti-androgenic effects on benign prostatic hyperplasia.
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Inhibidores de 5-alfa-Reductasa/uso terapéutico , Dutasterida/uso terapéutico , Receptor beta de Estrógeno/metabolismo , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Prostatitis/tratamiento farmacológico , Inhibidores de 5-alfa-Reductasa/farmacología , Animales , Modelos Animales de Enfermedad , Dutasterida/farmacología , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/genética , Interleucina-18/genética , Interleucina-18/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Síntomas del Sistema Urinario Inferior/inducido químicamente , Síntomas del Sistema Urinario Inferior/metabolismo , Masculino , Próstata/efectos de los fármacos , Próstata/metabolismo , Prostatitis/inducido químicamente , Prostatitis/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
AIMS: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) causes long-standing pain and/or storage symptoms. This study aimed to evaluate the likelihood of deterioration of bladder sensation in a carrageenan-induced CP/CPPS model by direct measurement of the bladder mechanosensitive single-unit afferent nerve activity. METHODS: In this study, male adult Sprague-Dawley rats were used. They were injected 50 µL of 3% λ-carrageenan or its vehicle (saline) into both lobes of the ventral prostate. Seven days following injection, the pain behavior at the pelvic-perineal area (using von Frey filaments), prostatic blood flow (using a laser blood flowmeter), and histology were examined along with cystometry (under conscious free-moving condition) and mechanosensitive single-unit afferent nerve activity (under urethane anesthesia). RESULTS: The prostate showed increased tissue weight and decreased blood flow and inflammatory cell infiltration in the carrageenan group compared to the control group. Consequently, the threshold of the pain behavior was decreased, and the basal and threshold pressures of the bladder were increased in the carrageenan group. In contrast, no significant differences of bladder histology and other cystometric parameters were found between the groups. Regarding Aδ- or C-fibers, the mechanosensitive afferent nerve activities revealed no differences in either group. CONCLUSIONS: The carrageenan-induced CP/CPPS rat model showed edema, ischemia, and inflammatory pain in the prostate, whereas a little change was detected in bladder sensation. These findings, which were evaluated using a direct measurement of the mechanosensitive single-unit afferent nerve activity, suggest that the bladder sensation is unlikely deteriorated in this model.
Asunto(s)
Carragenina , Dolor Pélvico/fisiopatología , Prostatitis/fisiopatología , Vejiga Urinaria/fisiopatología , Vías Aferentes/fisiopatología , Animales , Conducta Animal/fisiología , Masculino , Fibras Nerviosas Amielínicas/fisiología , Dimensión del Dolor , Dolor Pélvico/inducido químicamente , Prostatitis/inducido químicamente , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVES: This study was undertaken to reveal therapeutic effects and the preliminary mechanism of Chinese medicine formula Qianlie Tongli decoction (QTD) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: A total of 50 male C57BL/6 mice were randomly divided into five groups. All groups except the control group were injected subcutaneously T2 peptide emulsion, which induced the CP/CPPS model. After the induction of CP/CPPS, the model group was given normal saline by oral gavage while low-dose, medium-dose and high-dose groups were treated with Chinese medicine formula. Micturition habits and pain behaviour of mice were analysed for each group. Haematoxylin and eosin (H&E) staining was used to investigate prostate inflammation. The serum level of tumour necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA) kit. KEY FINDINGS: Chinese medicine formula significantly reduced the number of urine spots and improved pain response frequency in the medium-dose and high-dose group. The high-dose group showed reduced considerably inflammatory lesion and inflammatory cell infiltration than the low-dose and medium-dose groups. Serum levels of TNF-α in the high-dose group were significantly reduced compared with the model group. CONCLUSIONS: The results demonstrated the therapeutic effects of Qianlie Tongli decoction in CP/CPPS mice by analysing clinically relevant symptoms (urinary tract system, pelvic pain and prostate inflammation) and preliminarily explored the inflammatory-related treatment mechanisms by measuring TNF-α.
Asunto(s)
Dolor Crónico/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Dimensión del Dolor/efectos de los fármacos , Dolor Pélvico/tratamiento farmacológico , Fragmentos de Péptidos/toxicidad , Prostatitis/tratamiento farmacológico , Animales , Dolor Crónico/inducido químicamente , Dolor Crónico/metabolismo , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Dimensión del Dolor/métodos , Dolor Pélvico/inducido químicamente , Dolor Pélvico/metabolismo , Prostatitis/inducido químicamente , Prostatitis/metabolismo , Resultado del TratamientoRESUMEN
To explore the mechanism of microRNA-155 (miR-155) deficiency, protecting against experimental autoimmune prostatitis (EAP) in a toll-like receptor 4 (TLR4)-dependent manner. After wild-type (WT) and miR-155-/- mice were injected with complete Freund's adjuvant and prostate antigen to establish EAP model, half were randomly selected for injection with lipopolysaccharide (LPS, a TLR4 ligand). The following experiments were then performed: von Frey filaments, hematoxylin-eosin (HE) staining, real time quantitative polymerase chain reaction (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). And the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the level of Malondialdehyde (MDA) were detected by corresponding kits.miR-155-/- mice with prostatitis exhibited the attenuated pelvic tactile allodynia/hyperalgesia and the suppressed TLR4/nuclear factor-kappa B (NF-κB) pathway as compared with the WT mice with prostatitis. In addition, LPS enhanced the upregulation of miR-155 and the activation of the TLR4/NF-κB pathway in the prostatic tissues of WT mice with EAP. Furthermore, prostatitis mice had aggravated inflammation scores accompanying the increased interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, interferon-γ, IL-12, and MDA in prostatic tissues with the decreased IL-10, SOD and GSH-Px, and the unaltered IL-4. Compared with the mice from the WT + EAP group and the miR-155-/- + EAP + LPS group, mice from the miR-155-/- + EAP group had decreased inflammation and oxidative stress. miR-155 deficiency ameliorated pelvic tactile allodynia/hyperalgesia in EAP mice and improved inflammation and oxidative stress in prostatic tissues in a TLR4-dependent manner involving NF-κB activation, thereby exerting a therapeutic effect in chronic prostatitis treatment.
Asunto(s)
Enfermedades Autoinmunes/genética , Hiperalgesia/genética , MicroARNs/genética , FN-kappa B/genética , Prostatitis/genética , Receptor Toll-Like 4/genética , Animales , Enfermedades Autoinmunes/inducido químicamente , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/prevención & control , Modelos Animales de Enfermedad , Adyuvante de Freund/administración & dosificación , Regulación de la Expresión Génica , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/inmunología , Hiperalgesia/inducido químicamente , Hiperalgesia/inmunología , Hiperalgesia/prevención & control , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-12/genética , Interleucina-12/inmunología , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Lipopolisacáridos/farmacología , Masculino , Malondialdehído/inmunología , Malondialdehído/metabolismo , Ratones , Ratones Noqueados , MicroARNs/inmunología , FN-kappa B/inmunología , Estrés Oxidativo , Antígeno Prostático Específico/administración & dosificación , Prostatitis/inducido químicamente , Prostatitis/inmunología , Prostatitis/prevención & control , Transducción de Señal , Superóxido Dismutasa/genética , Superóxido Dismutasa/inmunología , Receptor Toll-Like 4/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
BACKGROUND: Prostate Cancer (PCa) is defined as a major health problem faced by the male population. AIM: We aimed to investigate the protective effects of Orange Peel Extract (OPE) and/or Selenium (Se) on chronic non-bacterial prostatitis in a rat model. METHODS: Fifty-six adult male Wistar albino rats were castrated; after 5 days, they were divided randomly into eight groups (n= 7). The control group received saline treatment; while 17ß-estradiol (E2) (0.25mg/kg) was injected subcutaneously in rats from Groups V, VI, VII, and VIII to induce chronic non-bacterial prostatitis. They were then treated with OPE (400mg/kg body weight; Groups II, IV, VI, and VIII) and/or sodium selenite (0.5mg/kg body weight; Groups III, IV, VII, and VIII) for 30 days. Interleukin-2 (IL2) and Prostate Cancer Antigen 3 (PCA3) mRNA expressions were determined using qPCR; Prostate-Specific Antigen (PSA) protein expression was determined immunohistochemically. Prostate tissue histology was examined by hematoxylin and eosin staining, and the levels of oxidative stress markers and antioxidant enzymes were measured. RESULTS: E2 administration significantly increased IL2 and PCA3 mRNA expressions, and PSA protein expression. It also increased the prostate wet weight and body weight, and lipid peroxidation, nitric oxide, TNF-α, and IL-1ß levels, decreased the glutathione and antioxidant enzyme levels and caused distinct histological alterations in the prostate gland. OPE and/or Se markedly improved all the studied parameters due to their antioxidant properties and anti-inflammatory effects. CONCLUSION: OPE and Se showed protective effects against 17ß-estradiol-induced chronic non-bacterial prostatitis. These results suggest that protection of chronic non-bacterial prostatitis by OPE+Se combination involves anti-oxidation and anti-inflammation. Moreover, their synergistic mechanism was mostly achieved via the regulation of oxidative stress and inflammation processes.
Asunto(s)
Citrus sinensis/química , Extractos Vegetales/farmacología , Prostatitis/prevención & control , Sustancias Protectoras/farmacología , Selenio/farmacología , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Estradiol/administración & dosificación , Inyecciones Subcutáneas , Masculino , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Prostatitis/inducido químicamente , Sustancias Protectoras/química , Sustancias Protectoras/aislamiento & purificación , Ratas , Ratas Wistar , Selenio/química , Relación Estructura-ActividadRESUMEN
Prostate inflammation (PI) is a clinical condition associated with infection and/or inflammation of the prostate. It is a common disease frequently associated to lower urinary tract (LUT) symptoms. The urethra is an understudied structure in the LUT and plays a fundamental role in the urinary cycle. Here, we proposed to evaluate the effect of PI on the urethra tissue. Male Sprague-Dawley rats were used, and PI was induced by formalin injection into the ventral lobes of the prostate. The pelvic urethra at the prostatic level was harvested for histological analysis, contraction (electrical field stimulation and phenylephrine), and relaxation (sodium nitroprusside/MK-571) experiments. Various gene targets [cytochrome c oxidase subunit 2, transforming growth factor-ß1, interleukin-1ß, hypoxia-inducible factor-1α, α1A-adrenoceptor, inositol 1,4,5-trisphosphate receptor type 1, voltage-gated Ca2+ channel subunit-α1D, neuronal nitric oxide synthase, soluble guanylyl cyclase, phosphodiesterase 5A, protein kinase CGMP-dependent 1, and multidrug resistance-associated protein 5 (MRP5; ATP-binding cassette subfamily C member 5)] were quantified, and cGMP levels were measured. No histological changes were detected, and functional assays revealed decreased contraction and increased relaxation of urethras from the PI group. The addition of MK-571 to functional assays increased urethral relaxation. Genes associated with inflammation were upregulated in urethras from the PI group, such as cytochrome oxidase c subunit 2, transforming growth factor-ß1, interleukin-1ß, and hypoxia-inducible factor-1α. We also found increased expression of L-type Ca2+ channels and the neuronal nitric oxide synthase enzyme and decreased expression of the MRP5 pump. Finally, cGMP production was enhanced in urethral tissue of PI animals. The results indicate that PI is associated with proinflammatory gene expression in the urethra without histologically evident inflammation and that PI produces a dysfunctional urethra and MRP5 pump downregulation, which results in cGMP accumulation inside the cell. These findings would help to better understand LUT dysfunctions associated with PI and the role of MRP pumps in the control of LUT function.