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ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis poses one of the biggest public health problems, necessitating the search for new therapeutic alternatives. For centuries, propolis has been widely used in folk medicine to treat various inflammatory and infectious diseases. Given its extensive use, it has excellent potential as an adjuvant treatment for patients with sepsis. OBJECTIVE: This study evaluated prophylactic treatment with standardized propolis extract (EPP-AF®) and followed the prognosis of sepsis induced by ligation and cecal ligation and puncture (CLP). METHODS: Initially, for survival assessment, Swiss mice were separated into five groups: Sham (false operated), control (PBS), ATB (received antibiotic, 8 mg/kg), P10 (received EPP-AF®, 10 mg/kg), and P100 (received EPP-AF®, 100 mg/kg). The animals received PBS, antibiotic, or EPP-AF® by the subcutaneous route 6 h before the CLP procedure. Animal survival was assessed every 12 h for five days when all of them were euthanized. RESULTS: We show that the treatment with EPP-AF® significantly increased the life expectancy of animals with sepsis compared to the control group. Interestingly, prophylactic treatment with EPP-AF® showed no effect on the number of colony-forming units in the peritoneum, blood, or lung. However, there was a decrease in cellular influx in the peritoneum. This alteration was unrelated to the number of bone marrow cells or the differential counting of peripheral blood cells. The coagulogram remained unchanged, including the number of platelets and prothrombin time-activated partial thromboplastin time. However, the inflammatory infiltrate and bleeding in the lung tissue were lower in the animals that received EPP-AF®. CONCLUSION: Thus, it was possible to conclude that prophylactic treatment with EPP-AF® preserved the lung parenchyma, resulting in an increased lifespan of mice with sepsis. It can be a helpful adjuvant in prophylactic treatment with antibiotics in presurgical conditions.
Assuntos
Própole , Sepse , Animais , Própole/farmacologia , Sepse/tratamento farmacológico , Sepse/mortalidade , Camundongos , Masculino , Abelhas , Pneumonia/prevenção & controle , Pneumonia/tratamento farmacológico , Modelos Animais de Doenças , Pulmão/efeitos dos fármacos , Pulmão/patologiaRESUMO
Sepsis is an organ dysfunction syndrome associated with high mortality. To date, no effective treatment is available to combat this disease. Punica granatum L. is a potential alternative treatment due to its anti-inflammatory, antimicrobial, and antioxidant properties. Thus, this study aimed to evaluate the effects of a hydroalcoholic crude extract from the peels of P. granatum (HCEPg) in mice with lethal sepsis. Lethal polymicrobial sepsis was induced in female Swiss mice via cecal ligation and puncture (CLP). Initially, the animals were divided into three groups: Sham (false-operated), CLP-control (phosphate-buffered saline), and CLP-HCEPg (single dose, 5 mg/kg, subcutaneous administration). Treatment was initiated immediately after the induction of sepsis, and survival was evaluated every 12 hr for 5 days. Those who survived were euthanized. Serum cytokine levels were measured using a cytometric bead array Mouse Inflammatory Cytokine Kit. The number of colony-forming units, as well as the number of cells in the lymphoid organs and their activation markers, were analyzed. Results showed that treatment with HCEPg increased lifespan and reduced bacterial counts in the peritoneum, bloodstream, and spleen. HCEPg also decreased hydrogen peroxide secretion by phagocytes and augmented serum IL-10 levels, indicating its systemic anti-inflammatory effects. Additionally, treatment with HCEPg attenuated infection-induced lung hemorrhage. Overall, P. granatum extract improved the lifespan of septic mice, possibly due to its antimicrobial, anti-inflammatory, and immunomodulatory effects, thereby regulating bacterial load and translocation, as well as controlling the systemic inflammation induced by sepsis.
Assuntos
Punica granatum , Sepse , Feminino , Animais , Camundongos , Longevidade , Sepse/tratamento farmacológico , Anticorpos , CitocinasRESUMO
Brazil is one of the countries that experienced an epidemic of microcephaly and other congenital manifestations related to maternal Zika virus infection which can result in Congenital Zika Syndrome (CZS). Since the Zika virus can modulate the immune system, studying mothers' and children's immune profiles become essential to better understanding CZS development. Therefore, we investigated the lymphocyte population profile of children who developed CZS and their mothers' immune response in this study. The study groups were formed from the Plaque Reduction Neutralization Test (PRNT) (CZS+ group) result. To evaluate the lymphocyte population profile, we performed phenotyping of peripheral lymphocytes and quantification of serum cytokine levels. The immunophenotyping and cytokine profile was correlated between CSZ+ children and their mothers. Both groups exhibited increased interleukin-17 levels and a reduction in the subpopulation of CD4+ T lymphocytes. In contrast, the maternal group showed a reduction in the population of B lymphocytes. Thus, the development of CZS is related to the presence of an inflammatory immune profile in children and their mothers characterized by Th17 activation.
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Microcefalia , Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Gravidez , Feminino , Humanos , Criança , Infecção por Zika virus/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Mães , Brasil/epidemiologiaRESUMO
The immunological mechanisms involved in the development of congenital Zika syndrome (CZS) have yet to be fully clarified. This study aims to assess the immuno-inflammatory profile of mothers and their children who have been diagnosed with CZS. Blood samples, which were confirmed clinically using the plaque reduction neutralization test (PRNT), were collected from children with CZS and their mothers (CZS+ group). Samples were also collected from children who did not develop CZS and had a negative PRNT result and from their mothers (CZS- group). The data demonstrated a correlation between the leukocyte profile of CZS+ children and their mothers, more evident in monocytes. Monocytes from mothers of CZS+ children showed low expression of HLA and elevated hydrogen peroxide production. CZS+ children presented standard HLA expression and a higher hydrogen peroxide concentration than CZS- children. Monocyte superoxide dismutase activity remained functional. Moreover, when assessing the monocyte polarization, it was observed that there was no difference in nitrite concentrations; however, there was a decrease in arginase activity in CZS+ children. These data suggest that ZIKV infection induces a maternal immuno-inflammatory background related to the child's inflammatory response after birth, possibly affecting the development and progression of congenital Zika syndrome.
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Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Gravidez , Criança , Feminino , Humanos , Infecção por Zika virus/diagnóstico , Peróxido de Hidrogênio , Imunidade , BrasilRESUMO
OBJECTIVE: To investigate the in vitro activity, synergism, cytotoxicity and cellular immunological response, as well as the molecular affinity between amphotericin B (AmB) and crotamine (CTA), derived from Crotalus durissus terrificus venom against Leishmania amazonensis. METHODS: This study performed the inhibition of promastigotes and amastigotes' growth under different concentrations of the drug and pharmacological combinations (AmB + CTA) based on the Berimbaum method (synergism study). The lactate dehydrogenase (LDH) quantification method was used to determine the cytotoxicity of the drug and combinations employing four cell lines (J774, HepG2, VERO, and C2C12). Following, the levels of Tumour Necrose Factor-alpha (TNF-α) and Interleukin-12 (IL-12) cytokines, using enzyme-linked immunosorbent assay (ELISA) and nitrites, as an indirect measure of Nitric Oxide (NO), using the Griess reaction were assessed in the supernatants of infected macrophages. In silico approach (molecular docking and dynamics) and binding affinity (surface plasmon resonance) between the drug and toxin were also investigated. RESULTS: CTA enhanced AmB effect against promastigote and amastigote forms of L. amazonensis, decreased the drug toxicity in different cell lines and induced the production of important Th1-like cytokines and NO by infected macrophages. The pharmacological combination also displayed consistent molecular interactions with low energy of coupling and a concentration-dependent profile. CONCLUSION: Our data suggest that this pharmacological approach is a promising alternative treatment against L. amazonensis infection due to the improved activity (synergistic effect) achieved against the parasites' forms and to the decreased cytotoxic effect.
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Antiprotozoários , Venenos de Crotalídeos , Anfotericina B/metabolismo , Anfotericina B/toxicidade , Animais , Antiprotozoários/farmacologia , Venenos de Crotalídeos/química , Crotalus/metabolismo , Citocinas/metabolismo , Simulação de Acoplamento Molecular , Óxido Nítrico/metabolismoRESUMO
Several natural products have been investigated for their bactericidal potential, among these, cinnamaldehyde. In this study, we aimed to evaluate the activity of cinnamaldehyde in the treatment of animals with sepsis induced by extraintestinal pathogenic E. coli. Initially, the E. coli F5 was incubated with cinnamaldehyde to evaluate the minimum inhibitory and minimum bactericidal concentration. Animal survival was monitored for five days, and a subset of mice were euthanized after 10 h to evaluate histological, hematological, and immunological parameters, as well as the presence of bacteria in the organs. On the one hand, inoculation of bacterium caused the death of 100% of the animals within 24 h after infection. On the other hand, cinnamaldehyde (60 mg/kg) was able to keep 40% of mice alive after infection. The treatment significantly reduced the levels of cytokines in serum and peritoneum and increased the production of cells in both bone marrow and spleen, as well as lymphocytes at the infection site. Cinnamaldehyde was able to reduce tissue damage by decreasing the deleterious effects for the organism and contributed to the control of the sepsis and survival of animals; therefore, it is a promising candidate for the development of new drugs.
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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.
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Adiposidade/fisiologia , Climatério/sangue , Leptina/sangue , Adulto , Fatores Etários , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Climatério/fisiologia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Fatores SocioeconômicosRESUMO
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
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Humanos , Feminino , Adulto , Idoso , Climatério/sangue , Leptina/sangue , Adiposidade/fisiologia , Fatores Socioeconômicos , Climatério/fisiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos de Coortes , Fatores Etários , Pessoa de Meia-IdadeRESUMO
Escherichia coli is an important pathogen responsible for a variety of diseases. We have recently shown that Pic, a serine protease secreted by E. coli, mediates immune evasion by the direct cleavage of complement molecules. The aim of this study was to investigate the action of a Pic-producing bacteria in a murine model of sepsis. Mice were infected with Pic-producing E. coli (F5) or F5∆pic mutant. Animal survival was monitored for five days, and a subset of mice was euthanized after 12 h for sample acquisition. The inoculation of Pic-producing bacteria induced 100% death within 24 h. The colony forming units count in the organs was significantly higher in F5. Hematological analysis showed a decrease of total leukocytes. Nitric oxide and cytokines were detected in serum, as well as on peritoneal lavage of the F5 group in higher levels than those detected in the other groups. In addition, immunophenotyping showed a decrease of activated lymphocytes and macrophages in the F5 group. Therefore, Pic represents an important virulence factor, allowing the survival of the bacterium in the bloodstream and several organs, as well as inducing a high production of proinflammatory mediators by the host, and concomitantly a cellular immunosuppression, leading to sepsis and death.
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Citocinas/metabolismo , Infecções por Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Sepse/metabolismo , Serina Endopeptidases/metabolismo , Animais , Citocinas/genética , Escherichia coli/genética , Escherichia coli/patogenicidade , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Proteínas de Escherichia coli/genética , Feminino , Inflamação/genética , Inflamação/metabolismo , Inflamação/microbiologia , Inflamação/patologia , Camundongos , Sepse/genética , Sepse/microbiologia , Sepse/patologia , Serina Endopeptidases/genéticaRESUMO
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.