RESUMEN

High-risk human papillomavirus (HPV) infection is associated with cervical cancer while low-risk HPV strains mostly cause benign lesions. Multiple studies have also associated HPV with coronary artery (CAD) disease in women. Furthermore, the climacteric period in women, triggers chronic inflammation and has major implications for CAD and associated lipid disorders. The association of HPV with coronary artery disease in climacteric women has few studies, and the objective of this review is to gather and analyse scientific data on the subject. This is an integrative review performed on PubMed and Google Scholar using the keywords "HPV", "coronary heart disease" and "climacteric", among these keywords the boolean operator AND and the publication date filter. (2018 onwards). Five articles were found, whose main results show presence of high-risk vaginal HPV in climacteric women. Climacterium and HPV were associated with a three-fold increased risk of CAD, as well as with factors related to menopause that promote atheroma formation, lipid disorders and chronic inflammation. Thus, these results support the association between HPV infection and CAD in climacteric women, possibly via chronic inflammation, hormonal factors related to menopause and dyslipidemia.

Asunto(s)

Menopausia , Infecciones por Papillomavirus , Humanos , Femenino , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/etiología , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/etiología

RESUMEN

Abstract High-risk human papillomavirus (HPV) infection is associated with cervical cancer while low-risk HPV strains mostly cause benign lesions. Multiple studies have also associated HPV with coronary artery (CAD) disease in women. Furthermore, the climacteric period in women, triggers chronic inflammation and has major implications for CAD and associated lipid disorders. The association of HPV with coronary artery disease in climacteric women has few studies, and the objective of this review is to gather and analyse scientific data on the subject. This is an integrative review performed on PubMed and Google Scholar using the keywords "HPV", "coronary heart disease" and "climacteric", among these keywords the boolean operator AND and the publication date filter. (2018 onwards). Five articles were found, whose main results show presence of high-risk vaginal HPV in climacteric women. Climacterium and HPV were associated with a three-fold increased risk of CAD, as well as with factors related to menopause that promote atheroma formation, lipid disorders and chronic inflammation. Thus, these results support the association between HPV infection and CAD in climacteric women, possibly via chronic inflammation, hormonal factors related to menopause and dyslipidemia.

Asunto(s)

Humanos , Femenino , Enfermedad de la Arteria Coronaria , Climaterio , Menopausia , Infecciones por Papillomavirus , Papillomaviridae

RESUMEN

Klotho proteins, αKlotho, ßKlotho, and γKlotho, exert tumor-suppressive activities via the fibroblast growth factor receptors and multiple cell-signaling pathways. There is a growing interest in Klotho proteins as potential diagnostic and prognostic biomarkers for multiple diseases. However, recent advances regarding their roles and potential applications in cancer remain disperse and require an integrated analysis. The present review analyzed research articles published between 2012 and 2022 in the Cochrane and Scopus scientific databases to study the role of Klotho in cancer and their potential as tools for diagnosing specific cancer types, predicting tumor aggressiveness and prognosis. Twenty-six articles were selected, dealing with acute myeloid leukemia and with bladder, breast, colorectal, esophageal, gastric, hepatocellular, ovarian, pancreatic, prostatic, pulmonary, renal, and thyroid cancers. αKlotho was consistently associated with improved prognosis and may be useful in estimating patient survival. A single study reported the use of soluble αKlotho levels in blood serum as a tool to aid the diagnosis of esophageal cancer. γKlotho was associated with increased aggressiveness of bladder, breast, and prostate cancer, and ßKlotho showed mixed results. Further clinical development of Klotho-based assays will require careful identification of specific tumor subtypes where Klotho proteins may be most valuable as diagnostic or prognostic tools.

RESUMEN

High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6 and HPV11, cause genital warts and laryngeal papillomas. However, the accumulating data suggests that HPV6 and HPV11 may cause malignant lesions at non-cervical anatomic sites. This review aims to estimate the proportions of single and dual HPV6/11 infections in multiple cancers reported in the last 10 years in the Cochrane, Embasa and PubMed databases. Secondly, the genomes of HPV6/11 were compared with the most common high-risk genotype, HPV16, to determine the similarities and differences. A total of 11 articles were selected, including between one and 334 HPV+ cancer patients. The frequencies of single or dual HPV6/11 infections ranged between 0-5.5% for penile and 0-87.5% for laryngeal cancers and were null for vulvar, vaginal and oral cancers. The genomic similarities between HPV6/11 and HPV16 mainly involved the E7 gene, indicating a limited ability to block cell differentiation. The presence of single or dual HPV6/11 infections in variable proportions of penile and laryngeal cancers support the vaccination strategies that cover these genotypes, not only for preventing genital warts but also for cancer prevention. Other risk factors and co-carcinogens are likely to participate in epithelial carcinogenesis associated with low-risk HPV.

RESUMEN

Human papillomavirus (HPV) infections are associated with cervical cancer and other anogenital cancers. Despite progresses in HPV vaccination and screening, these cancers still show high incidence and mortality, requiring improved prognostic markers and tailored therapies. This review addresses the role of Matrix metalloproteinases (MMPs) in HPV-induced cancers and the modulation of MMP expression by HPV oncoproteins. Scientific literature indexed in PubMed and ScienceDirect about Human papillomavirus modulates matrix metalloproteinases was retrieved and critically analyzed, to obtain an overview of expression patterns and their implications for carcinogenesis and patient prognosis. Matrix metalloproteinases such as MMP1, MMP9 and MMP13 have been associated with patient prognosis in HPV-induced cancers and play a major role in the degradation of the extracellular matrix, tumor invasion and metastasis. The HPV E2 and E7 oncoproteins regulate MMP expression via AKT, MEK/ERK and AP-1 signaling among other mechanisms. Increased expression of MMPs is associated with cancer progression and poor prognosis in multiple HPV-induced cancers, suggesting their potential use as prognostic markers. The identification of specific signaling pathways that mediate MMP regulation by HPV is essential for developing efficient new cancer therapies.

Asunto(s)

Alphapapillomavirus , Proteínas Oncogénicas Virales , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Humanos , Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/patología , Alphapapillomavirus/metabolismo , Metaloproteinasa 2 de la Matriz , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus , Neoplasias del Cuello Uterino/patología , Metaloproteinasas de la Matriz/metabolismo , Carcinogénesis/genética

RESUMEN

A growing proportion of oropharyngeal squamous cell carcinomas (OPSCC) are associated with infection by high-risk human papillomavirus (HPV). For reasons that remain largely unknown, HPV+OPSCC is significantly more common in men than in women. This study aims to determine the incidence of OPSCC in male and female HPV16-transgenic mice and to explore the role of female sex hormone receptors in the sexual predisposition for HPV+ OPSCC. The tongues of 30-weeks-old HPV16-transgenic male (n = 80) and female (n = 90) and matched wild-type male (n = 10) and female (n = 10) FVB/n mice were screened histologically for intraepithelial and invasive lesions in 2017 at the Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Portugal. Expression of estrogen receptors alpha (ERα) and beta (ERß), progesterone receptors (PR) and matrix metalloproteinase 2 (MMP2) was studied immunohistochemically. Collagen remodeling was studied using picrosirius red. Female mice showed robust ERα and ERß expression in intraepithelial and invasive lesions, which was accompanied by strong MMP2 expression and marked collagen remodeling. Male mice showed minimal ERα, ERß and MMP2 expression and unaltered collagen patterns. These results confirm the association of HPV16 with tongue base cancer in both sexes. The higher cancer incidence in female versus male mice contrasts with data from OPSCC patients and is associated with enhanced ER expression via MMP2 upregulation.

RESUMEN

BACKGROUND/AIM: Head-and-neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in the world and human papillomavirus (HPV) is an important risk factor for this neoplasm. Recent studies showed an association between sex hormone receptors and pathogenesis and/or prognosis in patients with HNSCC. The aim of this study was to clarify the expression patterns of sex hormone receptors in HPV-positive and HPV-negative HNSCC and their associations with tumour biopathology and biological behaviour. MATERIALS AND METHODS: Scientific literature indexed in PubMed about sex hormone receptors in HNSCC was retrieved and critically analyzed, to obtain an overview of expression patterns and their possible implications for tumour biopathology and prognosis. RESULTS: Sex hormone receptors were more frequently detected in oropharyngeal tumours compared with HNSCC from other locations. ERα was associated with HPV-positive tumours. The androgen and progesterone receptors were associated with poor patient prognosis. Estrogen receptor alpha (ERα) is implicated in the biopathology of HNSCC in different ways, by promoting DNA hypermutation and facilitating HPV integration thus contributing to an immunogenic phenotype, but also by cooperating with the epithelial growth factor receptor (EGFR) to promote resistance to therapy. CONCLUSION: The expression of sex hormone receptors may be of prognostic value in specific tumour subgroups, but the use of hormonal therapies for HNSCC is still not in close sight.

Asunto(s)

Neoplasias de Cabeza y Cuello/virología , Infecciones por Papillomavirus/complicaciones , Receptores de Esteroides/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Animales , Biomarcadores de Tumor/metabolismo , Femenino , Hormonas Esteroides Gonadales/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/terapia , Humanos , Masculino , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/virología , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia

RESUMEN

OBJECTIVE: Climacterium is associated with elevated leptin levels and increased risk of cardiovascular disorders. Conflicting data diverge on whether high leptin levels in climacterium reflect increasing adipose mass or, at least partially, age-related hormonal changes. This study addresses this issue in women from a Brazilian state with a low human development index. SUBJECTS AND METHODS: A case-control study was conducted, enrolling 136 women from the state of Maranhão, 52 (38.2%) climacteric and 84 (61.8%) non-climacteric. Biometric, biochemical, hormonal and immunological parameters were analyzed. RESULTS: Climacteric women showed a moderately increased waist/hip ratio (0.894 versus 0.834, p < 0.05), sustained body mass index (27.46 versus 28.68, p > 0.05) increased leptin levels (9.59 versus 7.13, p < 0.05) and no evidence of metabolic syndrome. No other parameters were altered. The climacteric cohort didn't show significant body fat gains but displayed a typical age-related redistribution of adipose tissue. Even so, leptin levels were significantly elevated compared with non-climacteric women. CONCLUSIONS: Altogether, these data support the hypothesis that leptin is elevated, at least partially, as a function of age and climacterium and is not necessarily correlated with metabolic dysfunction and systemic inflammation. Further studies are needed to evaluate the impact of higher leptin levels on postmenopausal women. Arch Endocrinol Metab. 2020;64(3):276-81.

Asunto(s)

Adiposidad/fisiología , Climaterio/sangre , Leptina/sangre , Adulto , Factores de Edad , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Climaterio/fisiología , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Factores Socioeconómicos

RESUMEN

ABSTRACT Objective Climacterium is associated with elevated leptin levels and increased risk of cardiovascular disorders. Conflicting data diverge on whether high leptin levels in climacterium reflect increasing adipose mass or, at least partially, age-related hormonal changes. This study addresses this issue in women from a Brazilian state with a low human development index. Subjects and methods A case-control study was conducted, enrolling 136 women from the state of Maranhão, 52 (38.2%) climacteric and 84 (61.8%) non-climacteric. Biometric, biochemical, hormonal and immunological parameters were analyzed. Results Climacteric women showed a moderately increased waist/hip ratio (0.894 versus 0.834, p < 0.05), sustained body mass index (27.46 versus 28.68, p > 0.05) increased leptin levels (9.59 versus 7.13, p < 0.05) and no evidence of metabolic syndrome. No other parameters were altered. The climacteric cohort didn't show significant body fat gains but displayed a typical age-related redistribution of adipose tissue. Even so, leptin levels were significantly elevated compared with non-climacteric women. Conclusions Altogether, these data support the hypothesis that leptin is elevated, at least partially, as a function of age and climacterium and is not necessarily correlated with metabolic dysfunction and systemic inflammation. Further studies are needed to evaluate the impact of higher leptin levels on postmenopausal women. Arch Endocrinol Metab. 2020;64(3):276-81

Asunto(s)

Humanos , Femenino , Adulto , Anciano , Climaterio/sangre , Leptina/sangre , Adiposidad/fisiología , Factores Socioeconómicos , Climaterio/fisiología , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios de Cohortes , Factores de Edad , Persona de Mediana Edad

RESUMEN

Lipopolysaccharide (LPS) induces fever through cytokines like receptor-activator of nuclear factor κB ligand (RANKL), triggering mediators like prostaglandins (PG), endothelin-1 (ET-1), corticotrophin-releasing factor (CRF), substance P (SP) and endogenous opioids. LPS-induced fever is reduced in females compared with males except in ovariectomized (OVX) females which show increased fever mediated by PG. The present study aimed to identify the mediators involved in fever in intact and OVX female rats. Fever was induced with LPS (50 µg/kg) intraperitoneally or CRF (2.5 µg), ET-1 (1 pg), morphine (10 µg) and SP (500 ng) intracerebroventricularly in sham-operated and OVX rats. The role of RANKL was evaluated with osteoprotegerin (OPG, 1 µg, intracerebroventricularly). Expression of RANK, CRFI/II, ETB, µ-opioid (MOR) and NK1 receptors was evaluated by confocal microscopy. Besides LPS, only morphine induced fever in OVX rats while all mediators induced fever in sham-operated animals. OPG abolished LPS-induced fever in OVX but not sham-operated animals. Overall, fever involves similar central mediators in cycling females and males but only morphine induced fever in OVX females. Importantly, RANK/RANKL participates in LPS-induced fever in OVX females, as in males but not in cycling females.

Asunto(s)

Citocinas/metabolismo , Fiebre/etiología , Hipotálamo/inmunología , Hipotálamo/metabolismo , Lipopolisacáridos/toxicidad , Ovariectomía/efectos adversos , Analgésicos Opioides/metabolismo , Animales , Hormona Liberadora de Corticotropina/metabolismo , Endotelina-1/metabolismo , Femenino , Fiebre/metabolismo , Fiebre/patología , Hipotálamo/efectos de los fármacos , Prostaglandinas/metabolismo , Ligando RANK/metabolismo , Ratas , Ratas Wistar , Sustancia P/metabolismo

RESUMEN

OBJECTIVE: To test the efficacy of Morus nigra L. (MN) leaf powder for treating climacteric symptoms by comparison with hormone therapy (HT) and placebo. METHODS: A randomized controlled trial among 62 climacteric women attending Hospital of the Federal University of Maranhão, Brazil. Women were divided into MN, HT, and placebo groups, and received 250 mg of MN leaf powder, 1 mg of estradiol, or placebo for 60 days. Primary outcomes were the Blatt-Kupperman index (BKI) for climacteric symptoms and SF-36 health questionnaire scores. RESULTS: Baseline sociodemographic variables, BKI scores, symptoms, and SF-36 domains did not differ among the groups. There was a reduction in mean BKI in the MN (17.5 vs 9.7, P<0.001), HT (15.4 vs 8.6, P=0.001), and placebo (16.1 vs 12.4, P=0.040) groups. Analysis of quality of life (QoL) showed that functional capacity (P=0.006), vitality (P=0.031), mental health (P=0.017), and social aspect (P<0.01) improved after treatment in the MN group. The HT group showed improvement in emotional limitation (P=0.040), and the placebo group showed better functional capacity (P=0.030) after treatment. CONCLUSIONS: Climacteric symptoms and QoL improved after administration of 250 mg of MN leaf powder for 60 days, similar to the effects of HT. The trial is registered in the Brazilian Registry of Clinical Trials (REBEC) under registration number RBR-9t4xxk.

Asunto(s)

Sofocos/tratamiento farmacológico , Morus , Extractos Vegetales/uso terapéutico , Calidad de Vida , Adulto , Brasil , Método Doble Ciego , Estradiol/uso terapéutico , Femenino , Humanos , Menopausia/fisiología , Persona de Mediana Edad , Encuestas y Cuestionarios

RESUMEN

OBJECTIVE: To evaluate the plasma cytokine levels during T cell-mediated inflammatory responses and compare the metabolic markers between overweight and obese perimenopausal women without systemic diseases. METHODS: Sixty perimenopausal women were divided into two groups (overweight and obese). Participants in both groups had their waist-to-height ratio (WHtR) measured and blood samples collected for the evaluation of estradiol, fasting glucose, leptin, high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-10, IL-17A levels, and lipid profile. RESULTS: In univariate analysis, women with obesity showed increased WHtR, fasting glucose, leptin, and IL-6 (p < 0.05) levels; however, significant differences were not observed in IL-10 or IL-17A (p > 0.05) levels. In the receiver operating characteristic curve, the highest areas under the curve were shown for leptin (0.856) and IL-6 (0.706). IL-6 levels correlated with both hs-CRP (r = 0.302, p = 0.020) and leptin (r = 0.294, p = 0.022). However, in multivariate analysis, IL-6 was not associated with a greater likelihood of obesity (OR = 1.61; 95% CI: 0.82-3.15; p = 0.16), when potential confounders were considered. CONCLUSION: IL-6 levels varied between overweight and obese perimenopausal women, and this association was weaker when adjusted for other clinical variables.

Asunto(s)

Citocinas/sangre , Obesidad Metabólica Benigna/sangre , Sobrepeso/sangre , Perimenopausia/sangre , Adulto , Índice de Masa Corporal , Brasil , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Estudios Transversales , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Interleucina-10/sangre , Interleucina-6/sangre , Leptina/sangre , Persona de Mediana Edad

RESUMEN

AIM: To investigate circulating hormonal, metabolic and inflammatory biomarker profiles in obese and non-obese middle-aged women. METHODS: A total of 110 women, aged 40-60 years, were included in this cross-sectional study. Patients were allocated, according to the occurrence of menopause and body mass index (BMI), into four groups: PM0 (premenopausal non-obese), PM1 (premenopausal obese), M0 (postmenopausal non-obese), and M1 (postmenopausal obese). Serum levels of gonadotropins, sex hormones, lipid markers, leptin, hs-CRP and interleukin-6 were obtained using either colorimetric or immunoenzymatic assays. Univariate and correlation analyses were performed among all clinical and laboratorial parameters. Principal component analysis was used to characterize subsets of biomarkers, which had their discriminatory capacity tested using discriminant function analysis. RESULTS: Levels of gonadotropins and female sex hormones were similar between PM0 and PM1 and between M0 and M1 (p > 0.05), all of them varied between PM0 and M0 (p < 0.05), but only estradiol was significantly altered in the comparison between PM1 and M1 (p = 0.027). Regarding metabolic markers, leptin was lower in PM0 than in M0 (p = 0.010) and higher in M1 than in M0 (p = 0.046). In premenopausal women, BMI correlated only to leptin, while it correlated to several other markers in postmenopausal women. A combination of FSH and leptin serum levels significantly discriminated the four groups (Wilks's lambda < 0.001, in canonical functions 1 and 2). CONCLUSION: A combined analysis of hormonal biomarkers may potentially distinguish obese from non-obese women with distinct menopause status. Further research is thus required to clarify the clinical significance of such findings.

Asunto(s)

Menopausia/metabolismo , Obesidad/metabolismo , Biomarcadores/sangre , Índice de Masa Corporal , Brasil/epidemiología , Proteína C-Reactiva/análisis , Estudios Transversales , Femenino , Hormonas Esteroides Gonadales/análisis , Hormonas Esteroides Gonadales/sangre , Gonadotropinas/análisis , Gonadotropinas/sangre , Humanos , Interleucina-6/análisis , Interleucina-6/sangre , Leptina/análisis , Leptina/sangre , Lípidos/análisis , Lípidos/sangre , Menopausia/sangre , Persona de Mediana Edad , Obesidad/fisiopatología , Posmenopausia/sangre , Premenopausia/sangre

RESUMEN

BACKGROUND: Cardiovascular diseases are leading causes of death worldwide. Recent studies suggest that infection by some viruses, including the human papillomavirus (HPV), may increase the risk of developing atheromatous lesions on coronary arteries. However, there is a lack of data regarding the possible association between HPV infection and coronary artery disease (CAD) in women. OBJECTIVE: To investigate whether HPV infection is associated with the occurrence of CAD among climacteric women. METHODS: The presence of CAD and cervical HPV DNA was investigated in 52 climacteric women. Social and demographic variables and metabolic profiles were also investigated. RESULTS: Among 27 women with CAD, 16 were positive for HPV, whereas 11 were negative. The presence of cervical HPV was strongly associated with CAD, after adjusting for demographic variables, health and sexual behaviors, comorbidities, and known cardiovascular risk factors. HPV-positive women showed a greater likelihood of having CAD (odds ratio [OR] = 3.74; 95% confidence interval [CI]: 1.16 to 11.96) as compared with HPV-negative women, particularly those infected with high-risk HPV types (OR = 4.90; 95% CI: 1.26 to 19.08). CONCLUSION: These results support the hypothesis that HPV infection might be associated with CAD among climacteric women, though further studies are needed to investigate the mechanisms involved.

Asunto(s)

Climaterio , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/etiología , Papillomaviridae , Infecciones por Papillomavirus/epidemiología , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Persona de Mediana Edad , Oportunidad Relativa , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Vigilancia en Salud Pública , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Factores Socioeconómicos

RESUMEN

Substance P (SP) is involved in fever that is induced by lipopolysaccharide (LPS) but not by interleukin-1ß or macrophage inflammatory protein-1α. Intracerebroventricular (i.c.v.) administration of the neurokinin-1 (NK1) receptor antagonist SR140333B in rats reduced fever that was induced by an i.c.v. injection of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), corticotropin-releasing factor (CRF), endothelin-1 (ET-1), and morphine (MOR). Furthermore, an i.c.v. injection of SP induced a febrile response that was inhibited by indomethacin concomitant with an increase in PGE2 levels in cerebrospinal fluid. Lipopolysaccharide and PGE2 caused higher expression and internalization of NK1 receptors in the hypothalamus which were prevented by SR140333B. These data suggest that SP is an important mediator of fever, in which it induces a prostaglandin-dependent response and is released after TNF-α, IL-6, PGE2, CRF, endogenous opioids, and ET-1.

Asunto(s)

Dinoprostona/líquido cefalorraquídeo , Fiebre/inducido químicamente , Fiebre/prevención & control , Pirógenos , Sustancia P/farmacología , Animales , Antiinflamatorios no Esteroideos/farmacología , Temperatura Corporal/efectos de los fármacos , Hormona Liberadora de Corticotropina/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Indometacina/farmacología , Interleucina-6/administración & dosificación , Interleucina-6/metabolismo , Masculino , Morfina/farmacología , Polisacáridos/toxicidad , Ratas , Ratas Wistar , Receptores de Neuroquinina-1/metabolismo , Sustancia P/metabolismo , Factores de Tiempo , Tropanos/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacología

RESUMEN

We previously reported that endothelin-1 (ET-1) reduced the frequency of spontaneous excitatory currents in vasopressinergic magnocellular cells through the activation of endothelin ETA receptors in rat brain slices. This effect was abolished by a cannabinoid CB1 receptor antagonist, suggesting the involvement of endocannabinoids. The present study investigated whether the blockade of ETA or CB1 receptors during the phase of increased levels of ET-1 after severe sepsis increases the survival rate of animals concomitantly with an increase in plasma arginine vasopressin (AVP) levels. Sepsis was induced in male Wistar rats by cecal ligation and puncture (CLP). Treatment with the CB1 receptor antagonist rimonabant (Rim; 10 and 20 mg/kg, orally) 4 h after CLP (three punctures) significantly increased the survival rate compared with the CLP per vehicle group. Intracerebroventricular treatment with the ETA receptor antagonist BQ123 (100 pmol) or with Rim (2 µg) 4 and 8 h after CLP but not the ETB receptor antagonist BQ788 (100 pmol), also significantly improved the survival rate. Sham-operated and CLP animals that were treated with Rim had significantly lower core temperature than CLP animals. However, oral treatment with Rim did not change bacterial count in the peritoneal exudate, neutrophil migration to the peritoneal cavity, leucopenia or increased plasma interleukin-6 levels induced by CLP. Both Rim and BQ123 also increased AVP levels 12 h after CLP. The blockade of central CB1 and ETA receptors in the late phase of sepsis increased the survival rate, reduced body temperature and increased the circulating AVP levels.

Asunto(s)

Arginina Vasopresina/metabolismo , Receptor Cannabinoide CB1/metabolismo , Receptor de Endotelina A/metabolismo , Sepsis/metabolismo , Animales , Arginina Vasopresina/sangre , Ciego/lesiones , Interleucina-6/sangre , Ligadura , Masculino , Ratas , Ratas Wistar , Receptor Cannabinoide CB1/sangre , Receptor de Endotelina A/sangre , Sepsis/sangre , Sepsis/etiología