Niels Olsen Saraiva Câmara

Universidade Federal do Triangulo Mineiro (UFTM), Убераба, Minas Gerais, Brazil

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Publications (200)582.1 Total impact

  • PLoS ONE 04/2015; 10(4):e0123753. DOI:10.1371/journal.pone.0123753 · 3.53 Impact Factor
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    ABSTRACT: Inflammatory bowel diseases (IBD) is the result of dysregulation of mucosal innate and adaptive immune responses. Factors such as genetic, microbial and environmental are involved in the development of these disorders. Accordingly, animal models that mimic human diseases are tools for the understanding the immunological processes of the IBD as well as to evaluate new therapeutic strategies. Crotoxin (CTX) is the main component of Crotalus durissus terrificus snake venom and has an immunomodulatory effect. Thus, we aimed to evaluate the modulatory effect of CTX in a murine model of colitis induced by 2,4,6- trinitrobenzene sulfonic acid (TNBS). The CTX was administered intraperitoneally 18 hours after the TNBS intrarectal instillation in BALB/c mice. The CTX administration resulted in decreased weight loss, disease activity index (DAI), macroscopic tissue damage, histopathological score and myeloperoxidase (MPO) activity analyzed after 4 days of acute TNBS colitis. Furthermore, the levels of TNF-α, IL-1β and IL-6 were lower in colon tissue homogenates of TNBS-mice that received the CTX when compared with untreated TNBS mice. The analysis of distinct cell populations obtained from the intestinal lamina propria showed that CTX reduced the number of group 3 innate lymphoid cells (ILC3) and Th17 population; CTX decreased IL-17 secretion but did not alter the frequency of CD4+Tbet+ T cells induced by TNBS instillation in mice. In contrast, increased CD4+FoxP3+ cell population as well as secretion of TGF-β, prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) was observed in TNBS-colitis mice treated with CTX compared with untreated TNBS-colitis mice. In conclusion, the CTX is able to modulate the intestinal acute inflammatory response induced by TNBS, resulting in the improvement of clinical status of the mice. This effect of CTX is complex and involves the suppression of the pro-inflammatory environment elicited by intrarectal instillation of TNBS due to the induction of a local anti-inflammatory profile in mice.
    PLoS ONE 04/2015; 10(4):e0121427. DOI:10.1371/journal.pone.0121427 · 3.53 Impact Factor
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    ABSTRACT: Formaldehyde (FA) is an environmental and occupational pollutant that induces programming mechanisms on the acquired immune host defense in offspring when exposed during the prenatal period. Hence, here we investigated whether the exposure of FA on pregnant rats could affect the development of an innate acute lung injury in offspring induced by lipopolissacaride (LPS) injection. Pregnant Wistar rats were exposed to FA (0.92mg/m(3)) or vehicle (distillated water), both 1h/day, 5 days/week, from 1 to 21 days of pregnancy. Non-manipulated rats were used as control. After 30 days of birth, the offspring was submitted to injection of LPS (Salmonella abortus equi, 5mg/kg, i.p.). Systemic and lung inflammatory parameters were evaluated 24h later. Exposure to FA during gestation abolished the development of acute lung injury in offspring, as observed by reduced number of leukocytes in the bronchoalveolar fluid (BAL), in the blood and in the bone marrow, and decreased myeloperoxidase activity in the lung. Moreover, phagocytes from BAL presented normal phagocytosis, but reduced oxidative burst. Alterations on the profile of inflammatory cytokines were evidenced by reduced mRNA levels of IL-6 and elevated levels of IL-10 and IFN gamma in the lung tissue. Indeed, mRNA levels of toll-likereceptor-4 and nuclear factor-kappa B translocation into the nucleus were also reduced. Additionally, hyperresponsiveness to methacholine was blunted in the trachea of offspring of FA exposed mothers. Together, our data clearly show that FA exposure in the prenatal period modifies the programming mechanisms of the innate defense in the offspring leading to impaired defense against infections. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Toxicology Letters 04/2015; 235(2). DOI:10.1016/j.toxlet.2015.04.001 · 3.36 Impact Factor
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    ABSTRACT: Diabetes and obesity are worldwide health problems. White fat dynamically participates in hormonal and inflammatory regulation. White adipose tissue is recognized as a multifactorial organ that secretes several adipose-derived factors that have been collectively termed " adipokines. " Adipokines are pleiotropic molecules that gather factors such as leptin, adiponectin, visfatin, apelin, vaspin, hepcidin, RBP4, and inflammatory cytokines, including TNF and IL-1í µí»½, among others. Multiple roles in metabolic and inflammatory responses have been assigned to these molecules. Several adipokines contribute to the self-styled " low-grade inflammatory state " of obese and insulin-resistant subjects, inducing the accumulation of metabolic anomalies within these individuals, including autoimmune and inflammatory diseases. Thus, adipokines are an interesting drug target to treat autoimmune diseases, obesity, insulin resistance, and adipose tissue inflammation. The aim of this review is to present an overview of the roles of adipokines in different immune and nonimmune cells, which will contribute to diabetes as well as to adipose tissue inflammation and insulin resistance development. We describe how adipokines regulate inflammation in these diseases and their therapeutic implications. We also survey current attempts to exploit adipokines for clinical applications, which hold potential as novel approaches to drug development in several immune-mediated diseases.
    Journal of Diabetes Research 04/2015; 2014:11. DOI:10.1155/2015/681612 · 3.54 Impact Factor
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    ABSTRACT: Short-chain fatty acids (SCFAs) are fermentation end products produced by the intestinal microbiota and have anti-inflammatory and histone deacetylase-inhibiting properties. Recently, a dual relationship between the intestine and kidneys has been unraveled. Therefore, we evaluated the role of SCFA in an AKI model in which the inflammatory process has a detrimental role. We observed that therapy with the three main SCFAs (acetate, propionate, and butyrate) improved renal dysfunction caused by injury. This protection was associated with low levels of local and systemic inflammation, oxidative cellular stress, cell infiltration/activation, and apoptosis. However, it was also associated with an increase in autophagy. Moreover, SCFAs inhibited histone deacetylase activity and modulated the expression levels of enzymes involved in chromatin modification. In vitro analyses showed that SCFAs modulated the inflammatory process, decreasing the maturation of dendritic cells and inhibiting the capacity of these cells to induce CD4(+) and CD8(+) T cell proliferation. Furthermore, SCFAs ameliorated the effects of hypoxia in kidney epithelial cells by improving mitochondrial biogenesis. Notably, mice treated with acetate-producing bacteria also had better outcomes after AKI. Thus, we demonstrate that SCFAs improve organ function and viability after an injury through modulation of the inflammatory process, most likely via epigenetic modification. Copyright © 2015 by the American Society of Nephrology.
    Journal of the American Society of Nephrology 01/2015; DOI:10.1681/ASN.2014030288 · 9.47 Impact Factor
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    ABSTRACT: Abstract Objective: To elucidate the effects of transcutaneous electrical nerve stimulation (TENS) in pregnancies with placental insufficiency. Methods: Pregnant rats were subjected to uterine artery ligation and to TENS according to the following groups: ligated stimulated (LS); ligated non-stimulated (LN), control stimulated (CS); and control non-stimulated (CN). Fetal external measurements, such as crown-rump length (CRL), fronto-occipital distance (FOD), thoracic ventral-dorsal (TVDD) and abdominal ventral-dorsal (AVDD) distances were analyzed together with the area occupied by fetal internal organs. Glucose transporter 1 (GLUT-1) expression was evaluated by immunohistochemistry in fetal organs. Thickness of junctional, labyrinth and intermediate placental zones was analyzed by morphometric evaluation in HE-stained slides, and placental hypoxia-inducible factor 1 alfa expression was measured by real-time polymerase chain reaction. Results: In LN and CS groups compared to the CN group, CRL was reduced (27.51/28.95 versus 30.16 mm), as well as FOD (6.63/6.63 versus 7.36 mm), AVDD (7.38/8.00 versus 8.61 mm) and TVDD (6.46/6.87 versus 7.23 mm). Brain GLUT-1 expression was higher in LS (1.3%) and CS (1.8%). The area occupied by placental vessels in the labyrinth zone (29.67 ± 3.51 versus 20.83 ± 7.63) and intermediate zone (26.46 ± 10.21 versus 10.86 ± 8.94) was larger in the LS group than in the LN group. Conclusions: Our results suggest a negative effect of TENS on placental development, thus compromising the maintenance of adequate blood flow to the fetus.
    Journal of Maternal-Fetal and Neonatal Medicine 01/2015; DOI:10.3109/14767058.2014.999034 · 1.21 Impact Factor
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    ABSTRACT: Acetylcholine (ACh) plays a crucial role in physiological responses of both the central and the peripheral nervous system. Moreover, ACh was described as an anti-inflammatory mediator involved in the suppression of exacerbated innate response and cytokine release in various organs. However, the specific contributions of endogenous release ACh for inflammatory responses in the lung are not well understood. To address this question we have used mice with reduced levels of the vesicular acetylcholine transporter (VAChT), a protein required for ACh storage in secretory vesicles. VAChT deficiency induced airway inflammation with enhanced TNF-α and IL-4 content, but not IL-6, IL-13 and IL-10 quantified by ELISA. Mice with decreased levels of VAChT presented increased collagen and elastic fibers deposition in airway walls which was consistent with an increase in inflammatory cells positive to MMP-9 and TIMP-1 in the lung. In vivo lung function evaluation showed airway hyperresponsiveness to methacholine in mutant mice. The expression of nuclear factor-kappa B (p65-NF-kB) in lung of VAChT-deficient mice were higher than in wild-type mice, whereas a decreased expression of janus-kinase 2 (JAK2) was observed in the lung of mutant animals. Our findings show the first evidence that cholinergic deficiency impaired lung function and produce local inflammation. Our data supports the notion that cholinergic system modulates airway inflammation by modulation of JAK2 and NF-kB pathway. We proposed that intact cholinergic pathway is necessary to maintain the lung homeostasis.
    PLoS ONE 01/2015; 10(3):e0120441. DOI:10.1371/journal.pone.0120441 · 3.53 Impact Factor
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    ABSTRACT: Adipose tissue is responsible for triggering systemic inflammatory response and these changes may be involved in the pathophysiology of preeclampsia. To characterize the lipid profile in the placenta of patients with early-onset preeclampsia. Samples were collected from placenta of 10 pregnant women with early-onset preeclampsia and 10 controls. Lipids were extracted using the Bligh-Dyer protocol and were analyzed by MALDI TOF-TOF mass spectrometry. The placental analysis of patients with preeclampsia revealed the main class glycerophosphoserines-GP03 (PS) as the most prevalent lipid, representing 56.28% of the total composition. Other main class found was macrolides/lactone polyketides-PK04 with 32.77%, both were increased in preeclamptic placentas when compared to the control group, PS (p<0.0001) and PK04 (p<0.0001). Some lipids found in placentas from patients with preeclampsia were reduced when compared to control group; glycerophosphoethanolamines-GP02 (Pet) (p<0.0001), glycerophosphoglycerols-GP04 (PG) (p<0.0001), glycerophosphoinositols-GP06 (PI) (p<0.0001), glycerophosphoinositol monophosphates-GP07 (p<0.0001), diradylglycerols-GL02 (p<0.0001), triradylglycerols-GL03 (p<0.0001), acidic glycosphingolipids-SP06 (GM3) (p<0. 0001), steroid conjugates-ST05 (p<0.0001), other acyl sugars-SL05 (p<0.0001) and flavonoids-PK12 (p<0.0001). Placental tissues from patients with preeclampsia expressed different lipid profile when compared to normal pregnant women. These findings suggest that specific lipidic species may be more associated with risk of developing preeclampsia than others. Interestingly, some of the lipids identified here have important cell functions that may be involved in the pathophysiology of preeclampsia. H.A. Korkes: None. N. Sass: None. A.F. Moron: None. N.O. Câmara: None. T. Bonetti: None. A.S. Cerdeira: None. I.D. Silva: None. L.G. De Oliveira: None. Copyright © 2014.
    01/2015; 5(1):74. DOI:10.1016/j.preghy.2014.10.149
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    ABSTRACT: Background Diseases of adulthood, such as diabetes and hypertension, may be related to changes during pregnancy, particularly in kidney. We hypothesized that acute kidney injury progresses more rapidly in cases of fetal programming.Methodsdiabetic dams' offspring were divided into: CC (controls, receiving vehicle); DC (diabetics, receiving vehicle); CA (controls receiving Folic Acid solution, 250 mg/kg); and DA (diabetics receiving Folic Acid solution). Renal function tests, morphometry, gene and protein expression of epithelial mesenchymal transition (EMT) markers was analyzed by qPCR and immunohistochemistry, respectively.ResultsCreatinine, urea, Bowman's space and EMT markers were increased in CA and DA groups. TGF-ß3, actin and fibronectin expression was higher in CA and DA, with significant increase in DA compared to CA 2-mo offspring. There was higher expression level of TGF-β1, TGF-β3, fibronectin, and vimentin in the offspring of diabetic dams at 5 months. Increases in TGF-β1 and TGF-β3 were more evident in the offspring of diabetic dams.Conclusions Fetal programming promotes remarkable changes in kidney morphology and function in offspring and renal failure progression may be faster in younger offspring of diabetic dams subjected to an additional injury.Pediatric Research (2014); doi:10.1038/pr.2014.205.
    Pediatric Research 12/2014; 77(3). DOI:10.1038/pr.2014.205 · 2.84 Impact Factor
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    ABSTRACT: Introduction Adipose tissue is responsible for triggering chronic systemic inflammatory response and these changes may be involved in the pathophysiology of preeclampsia. Objective To characterize the lipid profile in the placenta and plasma of patients with preeclampsia. Methodology Samples were collected from placenta and plasma of 10 pregnant women with preeclampsia and 10 controls. Lipids were extracted using the Bligh–Dyer protocol and were analysed by MALDI TOF-TOF mass spectrometry. Results Approximately 200 lipid signals were quantified. The most prevalent lipid present in plasma of patients with preeclampsia was the main class Glycerophosphoserines-GP03 (PS) representing 52.30% of the total lipid composition, followed by the main classes Glycerophosphoethanolamines-GP02 (PEt), Glycerophosphocholines-GP01 (PC) and Flavanoids-PK12 (FLV), with 24.03%, 9.47% and 8.39% respectively. When compared to the control group, plasma samples of patients with preeclampsia showed an increase of PS (p<0.0001), PC (p<0.0001) and FLV (p<0.0001). Placental analysis of patients with preeclampsia, revealed the PS as the most prevalent lipid representing 56.28%, followed by the main class Macrolides/polyketides-PK04 with 32.77%, both with increased levels when compared with patients control group, PS (p<0.0001) and PK04 (p<0.0001). Conclusion Lipids found in placenta and plasma from patients with preeclampsia differ from those of pregnant women in the control group. Further studies are needed to clarify if these changes are specific and a cause or consequence of preeclampsia.
    PLoS ONE 10/2014; 9(10):e110747. DOI:10.1371/journal.pone.0110747 · 3.53 Impact Factor
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    ABSTRACT: Nephrotoxicity is substantial side effect for 30% of patients undergoing cancer therapy with cisplatin and may force them to change or even abandon the treatment. Studies regarding aerobic exercise have shown its efficacy for the treatment of many types of diseases and its capacity to reduce tumors. However, little is known about the impact of physical exercise on cisplatin-induced acute kidney injury (AKI). In the present study, our aim was to investigate the role of physical exercise in AKI induced by cisplatin. We submitted C57Bl6 male mice to seven weeks of chronic exercise on a training treadmill and treated them with single i.p. injection of cisplatin (20 mg/kg) in the last week. Exercise efficacy was confirmed by an increased capillary-to-fiber ratio in the gastrocnemius muscle of exercised groups (EX and CIS-EX). The group submitted to exercise before cisplatin administration (CIS-EX) exhibited less weight loss and decreased serum urea levels compared to the cisplatin group (CIS). Exercise also showed a protective role against cisplatin-induced cell death in the kidney. The CIS-EX group showed a lower inflammatory response, with less TNF and IL-10 expression in the kidney and serum. In the same group, we observed an increase of IL-6 and HO-1 expression in the kidney. Taken together, our results indicate that chronic aerobic exercise is able to attenuate AKI by inducing IL-6 and HO-1 production, which results in lower inflammatory and apoptotic profiles in the kidney.
    PLoS ONE 10/2014; 9(10):e108543. DOI:10.1371/journal.pone.0108543 · 3.53 Impact Factor
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    ABSTRACT: Cisplatin treatment has been adopted in some chemotherapies; however, this drug can induce acute kidney injury due its ability to negatively affect renal function, augment serum levels of creatinine and urea, increase the acute tubular necrosis score and up-regulate cytokines (e.g., IL-1β and TNF-α). The kinin B2 receptor has been associated with the inflammation process, as well as the regulation of cytokine expression, and its deletion resulted in an improvement in the diabetic nephropathy status. To examine the role of the kinin B2 receptor in cisplatin-induced acute kidney injury, kinin B2 receptor knockout mice were challenged with cisplatin. Additionally, WT mice were treated with a B2 receptor antagonist after cisplatin administration. B2 receptor-deficient mice were less sensitive to this drug than the WT mice, as shown by reduced weight loss, better preservation of kidney function, down regulation of inflammatory cytokines and less acute tubular necrosis. Moreover, treatment with the kinin B2 receptor antagonist effectively reduced the levels of serum creatinine and blood urea after cisplatin administration. Thus, our data suggest that the kinin B2 receptor is involved in cisplatin-induced acute kidney injury by mediating the necrotic process and the expression of inflammatory cytokines, thus resulting in declined renal function. These results highlight the kinin B2 receptor antagonist treatment in amelioration of nephrotoxicity induced by cisplatin therapy.
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    ABSTRACT: Several studies have shown that estrogens mimic leptin's effects on energy balance regulation. However, the findings regarding the consequences of reduced sex hormone levels on leptin sensitivity are divergent. In the present study, we employed different experimental paradigms to elucidate the interaction between estrogens, leptin and energy balance regulation. We confirmed previous reports showing that ovariectomy caused a reduction in locomotor activity and energy expenditure leading mice to obesity and glucose intolerance. However, the acute and chronic anorexigenic effects of leptin were preserved in ovariectomized (OVX) mice despite their increased serum leptin levels. We studied hypothalamic gene expression at different time points after ovariectomy and observed that changes in the expression of genes involved in leptin resistance (suppressors of cytokine signaling and protein-tyrosine phosphatases) did not precede the early onset of obesity in OVX mice. On the contrary, reduced sex hormone levels caused an up-regulation of the long form of the leptin receptor (LepR), resulting in increased activation of leptin signaling pathways in OVX leptin-treated animals. The up-regulation of the LepR was observed in long-term OVX mice (30 days or 24 weeks after ovariectomy), but not 7 days after the surgery. In addition, we observed a progressive decrease in the co-expression of LepR and estrogen receptor-α in the hypothalamus after the ovariectomy resulting in a low percentage of dual-labeled cells in OVX mice. Taken together, our findings suggest that the weight gain caused by reduced sex hormone levels is not primarily caused by induction of a leptin resistance state.
    Endocrinology 08/2014; 155(11):en20141276. DOI:10.1210/en.2014-1276 · 4.64 Impact Factor
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    ABSTRACT: Obesity is an important worldwide challenge that must be faced in most developed and developing countries because of unhealthy nutritional habits. The consequences of obesity and being overweight are observed in different organs, but the kidney is one of the most affected. Excess adipose tissue causes hemodynamic alterations in the kidney that can result in renal disease. However, obesity is also commonly associated with other comorbidities such as chronic inflammation, hypertension and diabetes. This association of several aggravating factors is still a matter of concern in clinical and basic research because the pathophysiologic mechanisms surrounding chronic kidney disease development in obese patients remain unclear. This review will discuss the consequences of obesity in the context of renal injury.
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    ABSTRACT: AIM: To investigate a potential protective role of the kinin B2 receptor in a glycerol-induced rhabdomyolysis mouse model. METHODS: We separated 28 C57Bl/6 male mice into 4 groups: untreated WT animals, untreated B2 knockout mice, glycerol-treated WT and glycerol-treated B2 knockout mice. Glycerol-treated animals received one intramuscular injections of glycerol solution (50% v/v, 7 mL/kg). After 48 h, urine and blood samples were collected to measure creatinine and urea levels. Additionally, kidney samples were extracted for histological evaluation, and the mRNA expression levels of kinin B1 and B2 receptors and inflammatory mediators were measured by real-time polymerase chain reaction. RESULTS: Serum creatinine and urea levels showed differences between untreated wild-type and glycerol-treated wild-type mice (0.66 ± 0.04 vs 2.61 ± 0.53 mg/dL, P < 0.01; and 33.51 ± 2.08 vs 330.2 ± 77.7 mg/dL, P < 0.005), and between untreated B2 knockout mice and glycerol-treated knockout mice (0.56 ± 0.03 vs 2.23 ± 0.87 mg/dL, P < 0.05; and 42.49 ± 3.2 vs 327.2 ± 58.4 mg/dL, P < 0.01), but there was no difference between the glycerol-treated wild-type and glycerol-treated knockout mice. Glycerol was able to induce a striking increase in kinin B2 receptor expression (> 30 times, 31.34 ± 8.9) in kidney. Animals injected with glycerol had a higher degree of tubular injury than untreated animals. Wild-type and knockout mice treated with glycerol intramuscularly present kidney injury, with impairment in renal function. However, B2 knockout mice treated with glycerol did not show a different phenotype regarding kidney injury markers, when compared to the wild-type glycerol-treated group. CONCLUSION: We conclude that the kinin B2 receptor does not have a protective role in renal injury.
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    ABSTRACT: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation. This study sought to assess the effects of an exercise training program on cytokines and soluble TNF receptors in response to acute exercise in SLE women. Eight SLE women and ten sex-, age- and BMI-comparable healthy controls (HC) participated in this study. Prior to and after a 12-week aerobic exercise training program, cytokines and soluble TNF receptors were assessed at rest and in response to single bouts of acute moderate/intense exercise. HC performed the acute exercise bouts only at baseline. After the exercise training program, there was a decrease in resting sTNFR2 levels (P=0.025) and a tend to reduction IL-10 levels (P=0.093) in SLE. The resting levels of IL-6, IL-10, and TNF-α after the exercise training in SLE reached HC levels (P>0.05). In response to a single bout of acute moderate exercise, the area under the curve (AUC) of IL-10 was significantly reduced after the exercise training program in SLE (P=0.043), and the AUC of IL-10, IL-6, TNF-α, and sTNFR1 of SLE approached control values (P>0.05). In response to a single bout of acute intense exercise, the AUC of IL-10 was significantly reduced in SLE (P=0.015). Furthermore, the AUC of sTNFR2 tended to decrease after exercise training program in SLE (P=0.084), but it did not reach control values (P=0.001). An aerobic exercise training program attenuated the inflammatory milieu in SLE women, revealing a novel homeostatic immunomodulatory role of exercise in an autoimmunity condition.
    Journal of Applied Physiology 07/2014; 117(6). DOI:10.1152/japplphysiol.00486.2014 · 3.43 Impact Factor
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    ABSTRACT: Macrophages play a special role in the onset of several diseases, including acute and chronic kidney injuries. In this sense, tubule interstitial nephritis (TIN) represents an underestimated insult, which can be triggered by different stimuli and, in the absence of a proper regulation, can lead to fibrosis deposition. Based on this perception, we evaluated the participation of macrophage recruitment in the development of TIN. Initially, we provided adenine-enriched food to WT and searched for macrophage presence and action in the kidney. Also, a group of animals were depleted of macrophages with the clodronate liposome while receiving adenine-enriched diet. We collected blood and renal tissue from these animals and renal function, inflammation, and fibrosis were evaluated. We observed higher expression of chemokines in the kidneys of adenine-fed mice and a substantial protection when macrophages were depleted. Then, we specifically investigated the role of some key chemokines, CCR5 and CCL3, in this TIN experimental model. Interestingly, CCR5 KO and CCL3 KO animals showed less renal dysfunction and a decreased proinflammatory profile. Furthermore, in those animals, there was less profibrotic signaling. In conclusion, we can suggest that macrophage infiltration is important for the onset of renal injury in the adenine-induced TIN.
    Mediators of Inflammation 07/2014; 2014:291024. DOI:10.1155/2014/291024 · 2.42 Impact Factor
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    ABSTRACT: To investigate a potential protective role of the kinin B2 receptor in a glycerol-induced rhabdomyolysis mouse model. We separated 28 C57Bl/6 male mice into 4 groups: untreated WT animals, untreated B2 ¬knockout mice, glycerol-treated WT and glycerol-treated B2 knockout mice. Glycerol-treated animals received intramuscular injections of glycerol solution (50% v/v, 7 mL/Kg). After 48 hours, urine and blood samples were collected to measure creatinine and urea levels. Additionally, kidney samples were extracted for histological evaluation, and the mRNA expression levels of kinin receptors and inflammatory mediators were measured by qRT-PCR. Serum creatinine and urea levels showed differences between untreated wild-type and glycerol-treated wild-type mice, and between untreated B2 knockout mice and glycerol-treated knockout mice, but there was no difference between the glycerol-treated wild-type and glycerol-treated knockout mice. Glycerol was able to induce a striking increase in kinin B2 receptor expression. Animals injected with glycerol had a high degree of tubular injury. We conclude that the kinin B2 receptor does not have a protective role in renal injury. Wild-type and knockout mice treated with glycerol intramuscularly present kidney injury, with impairment in renal function. However, B2 knockout mice treated with glycerol did not show a different phenotype, when compared to the wild-type glycerol-treated group.
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    ABSTRACT: Cisplatin treatment has been adopted in some chemotherapies; however, this drug can induce acute kidney injury due its ability to negatively affect renal function, augment serum levels of creatinine and urea, increase the acute tubular necrosis score and up-regulate cytokines (e.g., IL-1β and TNF-α). The kinin B2 receptor has been associated with the inflammation process, as well as the regulation of cytokine expression, and its deletion resulted in an improvement in the diabetic nephropathy status. To examine the role of the kinin B2 receptor in cisplatin-induced acute kidney injury, kinin B2 receptor knockout mice were challenged with cisplatin. Additionally, WT mice were treated with a B2 receptor antagonist after cisplatin administration. B2 receptor-deficient mice were less sensitive to this drug than the WT mice, as shown by reduced weight loss, better preservation of kidney function, down regulation of inflammatory cytokines and less acute tubular necrosis. Moreover, treatment with the kinin B2 receptor antagonist effectively reduced the levels of serum creatinine and blood urea after cisplatin administration. Thus, our data suggest that the kinin B2 receptor is involved in cisplatin-induced acute kidney injury by mediating the necrotic process and the expression of inflammatory cytokines, thus resulting in declined renal function. These results highlight the kinin B2 receptor antagonist treatment in amelioration of nephrotoxicity induced by cisplatin therapy.
    International Immunopharmacology 06/2014; DOI:10.1016/j.intimp.2014.06.025 · 2.71 Impact Factor

Publication Stats

2k Citations
582.10 Total Impact Points

Institutions

  • 2015
    • Universidade Federal do Triangulo Mineiro (UFTM)
      Убераба, Minas Gerais, Brazil
  • 2006–2015
    • University of São Paulo
      • Department of Immunology (ICB)
      San Paulo, São Paulo, Brazil
  • 1999–2014
    • Universidade Federal de São Paulo
      • • Departamento de Medicina
      • • School of Medicine
      San Paulo, São Paulo, Brazil
  • 2007
    • Federal University of Juiz de Fora
      Juiz de Fora, Minas Gerais, Brazil
  • 2001–2004
    • Imperial College London
      • • Section of Immunology
      • • Faculty of Medicine
      Londinium, England, United Kingdom