RESUMO
Although sickle cell disease (SCD) and its manifestations have been associated with various lipid alterations, there are a few studies exploring the impact of sphingolipids in SCD. In this study, we determined plasma ceramide (Cer) and sphingomyelin (CerPCho) species and investigated their association with the crisis in SCD. SCD patients (N = 27) suffering from vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) were involved in this study. Blood samples were drawn at crisis and later at steady state periods. Clinical history, white blood cell count (WBC), C-reactive protein and lactate dehydrogenase (LDH) levels were recorded. 16:0, 18:0, 20:0, 22:0 Cer and 16:0, 18:0, 24:0 CerPCho were measured via LC-MS/MS. All measured Cer and CerPCho levels of SCD patients at crisis and steady-state were found to be similar. Inflammation-related parameters were significantly higher in patients with ACS compared to single-site VOC. Patients with multiple-site VOC were found to have significantly lower sphingolipid levels compared with those with single-site VOC, at crisis (16, 18, 24 CerPCho and 18, 22 Cer) and at steady-state (24:0 CerPCho and 18 Cer). Our results show that sphingolipid levels in SCD patients are similar during crisis and at steady state. However, lower sphingolipid levels appear to be associated with the development of multiple-site VOC. Since the differences were observed at both crisis and steady-state, sphingolipid level could be an underlying factor associated with crisis characteristics in patients with SCD.
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Anemia Falciforme , Ceramidas , Esfingolipídeos , Humanos , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Masculino , Feminino , Adulto , Esfingolipídeos/sangue , Ceramidas/sangue , Síndrome Torácica Aguda/sangue , Síndrome Torácica Aguda/etiologia , Esfingomielinas/sangue , Adulto Jovem , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Sphingolipid species in the lung epithelium have a critical role for continuity of membrane structure, vesicular transport, and cell survival. Sphingolipid species were reported to have a role in the inflammatory etiology of cystic fibrosis by previous work. The aim of the study was to investigate the levels of plasma sphingomyelin and ceramide in adult cystic fibrosis (CF) patients and compared with healthy controls. MATERIALS AND METHODS: Blood samples were obtained from CF patients at exacerbation (n = 15), discharge (n = 13) and stable periods (n = 11). Healthy individuals (n = 15) of similar age served as control. Levels of C16-C24 sphingomyelin and C16-C24 ceramide were measured in the plasma by LC-MS/MS. Also, cholesterol and triglyceride levels were determined in plasma samples of the patients at stable period. RESULTS: All measured sphingomyelin and ceramide levels in all periods of CF patients were significantly lower than healthy controls except C16 sphingomyelin level in the stable period. However, plasma Cer and SM levels among exacerbation, discharge, and stable periods of CF were not different. CF patients had significantly lower cholesterol levels compared to healthy individuals. We found significant correlation of cholesterol with C16 sphingomyelin. CONCLUSION: We observed lower plasma Cer and SM levels in adult CF patients at exacerbation, discharge, and stable periods compared to healthy controls. We didn't find any significant difference between patient Cer and SM levels among these three periods. Our limited number of patients might have resulted with this statistical insignificance. However, percentage of SM16 levels were increased at discharge compared to exacerbation levels, while percentage of Cer16 and Cer 20 decreased at stable compared to exacerbation. Inclusion of a larger number of CF patients in such a follow up study may better demonstrate any possible difference between exacerbation, discharge, and stable periods.
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BACKGROUND: Sickle cell disease (SCD) is an inflammatory disease that can result in both chronic and acute inflammation. Immature granulocytes (IG) are not-yet-mature white blood cells that can be easily detected in complete blood count (CBC) tests. In recent studies it has been suggested that IG may play a role in determining the prognosis of inflammatory diseases. The aim of our study was to investigate the role of IG percentage on predicting acute chest syndrome (ACS) and the severity of vaso-occlusive crisis (VOC) in patients with SCD. METHODS: The study cohort consisted of 49 SCD patients admitted to the emergency department for VOC. If symptoms did not regress despite appropriate treatment including hydration and analgesia, they were hospitalized. Patients whose symptoms regressed were discharged from the emergency department within 24 hours. Blood samples, including CBC and C-reactive protein (CRP), a marker of inflammation, were taken within the first hour of admission. Steady state laboratory parameters from the previous visit in the last three months were collected from patient files. RESULTS: The mean age was 18±4 (range 8-25) years. Most were hospitalized (41/49; 83.7%) and 8 of 49 were discharged from the emergency department after their treatment for VOC. ACS developed in 13 of 49 (26.5%). White blood cell, neutrophil and nucleated red blood cell counts, percentage of IG (IG%) and CRP levels were significantly increased in patients with VOC. IG% of patients with ACS was significantly higher than patients without ACS. However, ROC analysis showed that IG% was not associated with the development of ACS or hospitalization for VOC. CONCLUSIONS: Despite a small SCD cohort, the significant increase in the IG% in patients with VOC compared to their baseline values has suggested a role for IG% in predicting VOC. Although IG% was higher in ACS, its utility in predicting ACS was poor.
Assuntos
Síndrome Torácica Aguda , Anemia Falciforme , Síndrome Torácica Aguda/diagnóstico , Síndrome Torácica Aguda/etiologia , Adolescente , Adulto , Anemia Falciforme/complicações , Criança , Granulócitos , Humanos , Inflamação , Adulto JovemRESUMO
OBJECTIVE: This study aimed to examine patients with lead poisoning in terms of metabolomic profiles and bioactive lipids (oxysterols and sphingosine 1-phosphate [S1P]) before and after chelation therapy. METHODS: Consent was obtained from 42 individuals diagnosed with lead poisoning and blood and urine samples were collected before and after chelation therapy. The levels of 7-ketocholesterol (7-KC), cholestan-3b,5a,6b-triol (Ctriol), and S1P were measured via LC-MS/MS. Metabolomic analysis was performed via GC-MS. RESULTS: 7-KC and C-triol levels were detected higher before chelation therapy compared with after therapy (Pâ<â0.001 for both). S1P levels were measured higher before the therapy. The results also showed that sphingolipid metabolism-related pathways were affected by lead toxicity as well as other related pathways. CONCLUSION: This preliminary study showed that lipid metabolism is affected in lead exposure and chelation therapy is effective in reversing possible damage.
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Chumbo , Lipidômica , Cromatografia Líquida/métodos , Humanos , Metabolômica , Espectrometria de Massas em Tandem/métodosRESUMO
We investigated plasma YKL-40 levels and chitotriosidase (CHIT1) activity in patients with cystic fibrosis (CF) lung disease and evaluated clinically relevant factors that may affect their levels. Plasma samples were obtained from pediatric (n = 19) and adult patients (n = 15) during exacerbation, discharge, and stable period of the disease. YKL-40 levels and chitotriosidase activity were measured by enzyme-linked immunosorbent assay and fluorometric assay, respectively. Data were compared with healthy children and adults of similar age. YKL-40 levels of pediatric and adult CF patients at all periods were significantly higher than controls (p < 0.001 and p < 0.05). CHIT1 activities of adult patients at all periods were significantly higher compared to controls (p < 0.05). On the other hand, CHIT1 activities of pediatric CF patients were similar with controls. YKL-40 levels of exacerbation period of adult CF patients were negatively correlated with forced vital capacity (FVC) (r = - 0.800, p = 0.014) and forced expiratory volume in 1 s (FEV1) (r = - 0.735, p = 0.008). YKL-40 levels in the exacerbation period of pediatric CF patients were negatively correlated with FVC (r = - 0.697, p = 0.0082) and FEV1 (r = - 0.720, p = 0.006). CHIT1 activity may be a valuable marker of chronic inflammation in adult CF patients who suffer from CF for a longer period compared to pediatric patients. Increased YKL-40 levels in both pediatric and adult patients compared to controls may point to a role in between CF pathology.
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Fibrose Cística , Adulto , Criança , Proteína 1 Semelhante à Quitinase-3 , Hexosaminidases , Humanos , Testes de Função RespiratóriaRESUMO
The aims of this study were to determine the possible relationships between the levels of hemin, hemopexin, acid sphingomyelinase, nitrite/nitrate (NOx), and other parameters in patients with SCD and to assess whether they were associated with vaso-occlusive crises (VOCs) or acute chest syndrome (ACS). Patients with SCD (homozygous or sickle beta-thalassemia) who were confirmed to have VOC or ACS were included. Blood samples were obtained at admission, on the third day of hospitalization, and at steady state. Demographic characteristics, pain (visual analog scale), complication history, complete blood count, lactate dehydrogenase, and C-reactive protein levels were recorded. Hemin, hemopexin, acid sphingomyelinase, and NOx were measured via ELISA. A total of 31 patients (22 VOC, 9 ACS) were included. Mean age was 16.4 ± 4.7 years. Admission white blood cell count and C-reactive protein levels were significantly higher in the ACS group. Patients with ACS also demonstrated a significant decreasing trend of LDH and an increasing trend of NOx values from admission to steady state. Notably, hemopexin levels were significantly lower on the third day of hospitalization compared to steady-state levels. Despite limited patient count in the ACS group, these patients appear to have strikingly greater inflammatory activation at admission, and the progression of ACS may be associated with LDH and NOx levels. Lower hemopexin levels during hospitalization versus steady state appear to support a role for the administration of hemopexin therapy during crises.
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Síndrome Torácica Aguda/complicações , Anemia Falciforme/complicações , Hemólise , Hemopexina/análise , Inflamação/complicações , Síndrome Torácica Aguda/sangue , Adolescente , Adulto , Anemia Falciforme/sangue , Criança , Progressão da Doença , Feminino , Humanos , Inflamação/sangue , Masculino , Adulto JovemRESUMO
Sickle cell disease (SCD) is a mortal erythrocyte-based disease which is hard to treat effectively. Development of a treatment method that can prevent deoxygenation of erythrocytes or reduce the oxidative stress of sickle erythrocytes is one of the important issues towards SCD. Among a wide variety of potential drug carriers, liposomes are advantageous and preferable with their easy preparation and biocompatibility. In this study, L-Glutamine (Gln) loaded liposomes were prepared with 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-Dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DPPG). Liposomes were characterized via zeta potential, size measurements, differential scanning calorimetry, Fourier Transform Infra-red Spectroscopy and they were visualized via transmission electron microscopy and scanning electron microscopy. Effect of the encapsulated amount of Gln was investigated by encapsulating Gln at three different concentrations (i.e0.20 mM, 40 mM and 60 mM). Drug encapsulation and release studies were implemented with high pressure liquid chromatography (HPLC). The encapsulation efficiency of Gln was determined to be the higher than the ones reported in the literature: 83.6%, 87.1% and 84.9% for 20 mM, 40 mM and 60 mM Gln, respectively. It was found that after 6 hours, liposomes loaded with 60 mM of Gln had released 45.7% of Gln. Optical microscopy images of the erythrocytes after 3 hours of incubation and haemolysis measurements proved that presence of liposomes did not cause any structural changes on the erythrocyte shape. Overall, it was concluded that L-Gln loaded PC/PG liposomes provide promising results in terms of developing a new drug delivery platform for SCD.
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Glutamina , Lipossomos , Eritrócitos , Fosfatidilcolinas , FosfatidilgliceróisRESUMO
We investigated plasma sphingomyelin (CerPCho) and ceramide (Cer) levels in pediatric patients with cystic fibrosis (CF) and primary ciliary dyskinesia (PCD). Plasma samples were obtained from CF (n = 19) and PCD (n = 7) patients at exacerbation, discharge, and stable periods. Healthy children (n = 17) of similar age served as control. Levels of 16-24 CerPCho and 16-24 Cer were measured by LC-MS/MS. Concentrations of all CerPCho and Cer species measured at exacerbation were significantly lower in patients with CF than PCD. 16, 18, 24 CerPCho, and 22, 24 Cer in exacerbation; 18, 24 CerPCho, and 18, 20, 22, 24 Cer at discharge; 18, 24 CerPCho and 24 Cer at stable period were significantly lower in CF patients than healthy children (p < 0.001 and p < 0.05). All CerPCho and Cer levels of PCD patients were significantly higher except 24 CerPCho and 24 Cer during exacerbation, 24 CerPCho at discharge, and 18, 22 CerPCho levels at stable period (p < 0.001 and p < 0.05) compared with healthy children. There was no significant difference among exacerbation, discharge, and stable periods in each group for Cer and CerPCho levels. This is the first study measuring plasma Cer and CerPCho levels in PCD and third study in CF patients. The dramatic difference in plasma levels of most CerPCho and Cer species found between two diseases suggest that cilia pathology in PCD and CFTR mutation in CF seem to alter sphingolipid metabolism possibly in opposite directions.
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Ceramidas/sangue , Transtornos da Motilidade Ciliar/sangue , Transtornos da Motilidade Ciliar/genética , Fibrose Cística/sangue , Esfingomielinas/sangue , Adolescente , Estudos de Casos e Controles , Criança , Cromatografia Líquida , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Humanos , Masculino , Proteínas Associadas aos Microtúbulos/genética , Mutação , Estudos Prospectivos , Espectrometria de Massas em TandemRESUMO
Silicosis is one of the prolonged and irreversible occupational diseases. Crystalline silica dust, which has been linked with silicosis, occurs in different industrial areas such as constructions, ceramic, quarry, and pottery. There are significant numbers of newly diagnosed cases every year in Turkey. Patients with silicosis suffer from inflammatory respiratory disorders and silicosis-related complications such as rheumatoid arthritis, systemic sclerosis, and vasculitis. Oxysterols are defined as 27-carbon intermediates or end products of cholesterol. They are also implicated in the etiology of disease states such as atherosclerosis, neurodegenerative, and inflammatory diseases. The aim of the study is to evaluate cholesterol oxidation products in the patients with silicosis and determination of sphingosine-1-phosphate (S1P) levels which is a sphingolipid metabolite. In addition to these parameters, it is aimed to determine the possible lipid peroxidation by different parameters. For this purpose, blood samples and urine were collected from 47 patients and 30 healthy individual with their consents. In order to evaluate oxysterols, 7-ketocholesterol and cholestan 3ß,5α,6ß-triol levels were measured by LC-MS/MS method. The measured levels of 7-KC were 0.101 ± 0.005 µmol/l in patient and 0.050 ± 0.003 µmol/l in control plasma samples. Triol levels were measured as 0.038 ± 0.005 µmol/l in patient group and 0.033 ± 0.004 µmol/l in control group (p < 0.001). In addition, lipid peroxidation products were measured by human-8-isoprostane, human-4-hydroxynonenal (4-HNE), and human malondialdehyde (MDA) ELISA kits. The measured levels of HNE in the patient and control groups were 735.14 ± 288.80 pg/ml and 595.72 ± 108.62 pg/ml in plasma and 606.02 + 118.23 pg/ml and 531.84 + 107.18 pg/ml in urine, respectively (p < 0.05). F2-iP results of patients and controls were 450.0 + 101.40 pg/dl and 386.9 + 112.7 pg/ml for urine and 432.7 ± 188,8 pg/dl and 321.9 ± 69.4 pg/dl for plasma, respectively (p < 0.05). MDA levels of plasma were measured as 44.1 ± 14.6 nmol/ml in the patient and 31.9 ± 10.5 nmol/ml in the control (p < 0.05). Levels of MDA for urine samples were 30.15 + 5.06 nmol/ml and 25.15 + 6.07 nmol/ml in patients and controls, respectively (p < 0.05). S1P levels were decreased in patients compared to control group (49.05 ± 10.87 and 67.57 ± 16.25, p < 0.001). The results not only indicate a correlation between cholesterol oxidation, lipid peroxidation, and silicosis, but also provide better understanding of the role of the lipids in the mechanism of this inflammatory disease.
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Oxisteróis/análise , Silicose/sangue , Silicose/urina , Adulto , Estudos de Casos e Controles , Cromatografia Líquida , Humanos , Cetocolesteróis/sangue , Cetocolesteróis/urina , Peroxidação de Lipídeos , Lisofosfolipídeos , Masculino , Pessoa de Meia-Idade , Oxisteróis/sangue , Oxisteróis/urina , Esfingosina/análogos & derivados , Espectrometria de Massas em Tandem , TurquiaRESUMO
In the present study, the possible activation of cellular immunity in SCD patients was investigated. As immune activation parameters, neopterin concentrations and kynurenine/tryptophan ratio for tryptophan degradation in 35 pediatric patients with sickle cell disease (31 HbSS and 4 HbSß) were determined. Our results have shown that neopterin levels (both urinary and serum) are increased in pediatric patients with sickle cell disease. The increase in neopterin concentration was accompanied by significantly increased biopterin, kynurenine concentration and kynurenine/tryptophan ratio. The mechanism of immune activation and the effects of inflammatory mediators in sickle cell disease are poorly understood, especially in terms of cell-mediated immunity. Further in-vivo and in-vitro studies are required to illuminate the association between neopterin levels and neutrophil activation in sickle cell disease.
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Anemia Falciforme/sangue , Anemia Falciforme/urina , Neopterina/sangue , Neopterina/urina , Adolescente , Anemia Falciforme/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Inflamação/urina , Masculino , Neopterina/imunologia , Ativação de Neutrófilo , Neutrófilos/imunologia , Neutrófilos/metabolismoRESUMO
BACKGROUND: Hypocholesterolemia is the most frequently encountered lipid abnormality in sickle cell disease (SCD). We enrolled pediatric patients to determine the relationships between lipid profile and parameters of hemolysis, oxidative stress and chronic inflammation in SCD. METHODS: The study involved 35 pediatric SCD patients and 19 healthy controls. Patients were crisis-free and had not received transfusions for the last 3 months. Total cholesterol, triglyceride, HDL-C, LDL-C, VLDL-C, apolipoprotein A1, apolipoprotein B, LCAT, LDH, bilirubin, haptoglobin, iron, ferritin, hemin, serum amyloid A (SAA), myeloperoxidase (MPO), uric acid, ALT and GGT levels were evaluated in patients' blood. RESULTS: Patients had hypocholesterolemia depicted by lower levels of total cholesterol, HDL-C, LDL-C, as well as Apolipoprotein A1 and Apolipoprotein B compared to controls. The chronic hemolysis of SCD was evident in patients by higher LDH and bilirubin and almost undetectable haptoglobin levels. Hemin levels (as a measure of oxidized heme) were significantly increased in patients with SCD. Inflammation markers, SAA and MPO, were significantly increased in the patients as well. There were negative correlations between HDL-C and LDH, and Apo A1 and SAA. Hemin was positively correlated to MPO. CONCLUSION: Hemolysis was associated with decreased HDL -C, and Inflammation was linked to decreased apolipoprotein A1 levels in our SCD patients. Therefore, we suggest that the HDL particle is altered during the course of the disease. The altered HDL in SCD may become dysfunctional and result with a slowing down of the reverse cholesterol transport.
Assuntos
Anemia Falciforme/sangue , Apolipoproteína A-I/sangue , Colesterol/sangue , Inflamação/sangue , Adolescente , Adulto , Anemia Falciforme/metabolismo , Anemia Falciforme/patologia , Apolipoproteína A-I/genética , Apolipoproteínas B/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Criança , Colesterol/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , VLDL-Colesterol/sangue , Feminino , Hemólise , Humanos , Inflamação/metabolismo , Inflamação/patologia , L-Lactato Desidrogenase/sangue , Lipídeos/sangue , Masculino , Peroxidase/sangue , Proteína Amiloide A Sérica/metabolismo , Triglicerídeos/sangue , Adulto JovemRESUMO
Sickle cell disease (SCD) causes anemia, oxidative stress, chronic inflammation, and lipid abnormalities. Oxysterols are oxidized derivatives of cholesterol and affect cholesterol metabolism and eryptosis. Our aim was to determine whether the plasma concentrations of 7-ketocholesterol (7-KC) and cholestane-3ß,5α,6ß-triol (C-triol) were associated with hemolysis and lipid profile in patients with SCD. A total of 32 steady-state pediatric patients with SCD (22 HbSS and 10 HbSß+) and 25 healthy controls were included in the study. Hemolysis parameters, ferritin, serum iron, lipids, 7-KC and C-triol concentrations of all subjects were measured. Oxysterols were quantified with N,N-dimethylglycine derivatization via LC-MS/MS. 7-KC and C-triol concentrations were found to be increased in SCD patients, while there was no difference between the HbSS and HbSß+ subgroups. 7-KC concentrations s were correlated negatively with hemoglobin and positively with lactate dehydrogenase concentrations, while C-triol concentrations were negatively correlated with HDL cholesterol. Furthermore, while 7-KC and C-triol concentrations were highly correlated among controls, there was no correlation in patients. The findings of our study suggest that 7-KC and C-triol may have a role in SCD pathophysiology. The lack of correlation in patients' 7-KC and C-triol concentrations suggest alterations in oxysterol production in patients with SCD.
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Anemia Falciforme/complicações , Anemia/complicações , Colesterol/sangue , Pirimidinas/sangue , Adolescente , Anemia/sangue , Anemia Falciforme/sangue , Criança , Colestanóis/sangue , Feminino , Ferritinas/sangue , Hemólise , Humanos , Ferro/sangue , Cetocolesteróis/sangue , Lipídeos/sangue , Masculino , Estresse Oxidativo , Adulto JovemRESUMO
We investigated vitamin D deficiency in pediatric sickle cell disease patients and its association with selected bone, lipid and inflammatory parameters. The study included 64 patients (33 SS and 31 SB) and 21 carriers (AS). Blood was obtained to assess levels of vitamin D, WBC, CRP, Ca, P, ALP, PTH, triglyceride, total cholesterol, LDL, VLDL, HDL, IL-2, IL-12, TNF-α, IL-4, IL-6, IL-10 and regulatory T cells. The patients were grouped according to their genotype (SS, SB) and vitamin D status (low or normal). Carriers were also grouped as low or normal vitamin D. Laboratory findings were similar between low and normal Vit D groups in SS, SB and AS genotypes except a lower IL-12 in SB-low vitamin D compared SB-normal vitamin D group. Acute chest syndrome was more frequent in SS-low Vit D (63%) compared to SS-normal Vit D (25%), SB-low Vit D (21%) and SB-normal Vit D (33%) (P = 0.045). Both SS and SB with low vitamin D had higher VLDL (P = 0.006 and P = 0.022), TNF-α (P = 0.001) and regulatory T cells (P = 0.000) compared to AS-low vitamin D. Both SS and SB with normal vitamin D had higher levels of regulatory T cells (P = 0.000) compared to AS-normal vitamin D. Vit D was not a modifier of selected inflammation, bone and lipid parameters in sickle cell disease. Acute chest syndrome was comparably more frequent in SS-low vitamin D. Increase of regulatory T cells in the patients was a result of chronic inflammation in sickle cell disease.
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OBJECTIVE: This study aimed to determine the association between the severity of obstructive sleep apnea (OSA) and the serum leptin level in non-obese OSA patients. METHODS: This prospective case-control study included non-obese OSA patients that presented with sleep-related disturbances and underwent polysomnography (PSG) between April 2015 and June 2016. The serum leptin level was measured and its relationship to PSG parameters was investigated. RESULTS: The study included 73 OSA patients (20 female and 53 male) with a mean age of 41.1±11.5 years and mean body-mass index (BMI) of 26.4±2.7kgm-2. The serum leptin level in 44 patients with moderate/severe OSA (AHI ≥15) was 3.4±2.6ngmL-1, versus 4.5±3.8ngmL-1 in 29 patients with snoring/mild OSA (AHI <15) (P=0.20). There were not any correlations between any of the PSG parameters and the serum leptin level, but there was a significant correlation between the leptin level and BMI (r=0.345, P<0.01). CONCLUSION: The serum leptin level does not differ significantly between non-obese OSA patients with moderate/severe and snoring/mild OSA. Obesity is the primary factor associated with the serum leptin level.
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Leptina/sangue , Apneia Obstrutiva do Sono/sangue , Ronco/sangue , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
Myoglobinuric acute renal failure (MARF) may develop after severe muscle injury. Heme oxygenase-1 (HO-1), a stress-response protein, has been implicated as a protective agent against MARF. We hypothesized that hyperbaric oxygen therapy (HBOT) may alleviate MARF by inducing renal HO-1 expression. Wistar-Albino rats were randomly assigned into three groups: Control (n = 4), MARF (n = 8), MARF + HBO (n = 8). MARF was induced by intramuscular glycerol (50%, 8 mL/kg) injection. Saline (8 mL/kg) was injected into the hind limb of the animals in the control group. Animals in the MARF + HBO group received two sessions of HBO therapy (90 min at 2.5 atm) 2 and 18 h after glycerol injection. Serum and tissue samples were taken at 24 h. Serum urea and creatinine levels increased in the MARF and MARF + HBO groups confirming the development of MARF. But, serum urea and creatinine levels were similar in MARF and MARF + HBO groups. Oxidative stress parameters were similar among all groups. Histological renal injury score was similar in MARF and MARF + HBO groups. HO-1 level, determined by immunohistochemistry, was significantly higher in MARF and MARF + HBO groups, compared to the control group. Although HO-1 level in MARF + HBO group was higher than MARF group, it was not statistically significant. We found that HBOT did not reduce renal injury in experimental MARF model. HBOT is used to reduce the muscle damage after crush injury, which may be accompanied by MARF. Therefore, more studies are needed to understand the effects of HBO treatment on renal functions after MARF.
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Injúria Renal Aguda/terapia , Creatinina/metabolismo , Oxigenoterapia Hiperbárica/métodos , Mioglobinúria/complicações , Rabdomiólise/complicações , Superóxido Dismutase/metabolismo , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Animais , Nitrogênio da Ureia Sanguínea , Modelos Animais de Doenças , Testes de Função Renal , Masculino , Mioglobinúria/diagnóstico , Mioglobinúria/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Rabdomiólise/diagnósticoRESUMO
PURPOSE: To investigate the possible protective effect of rutin on methotrexate induced hepatotoxicity in rats. METHODS: Twenty-two rats were divided into three experimental groups; Control-saline, Mtx, Mtx+Rutin. Hepatic tissue was taken for histological assessment and biochemical assays. Oxidative stress parameters malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were investigated. Liver markers aspartate aminotransferase (AST), alanine aminotransferase (ALT) were analyzed in serum. RESULTS: Mtx+Rutin group showed lower histological injury compared to Mtx group, MDA and ALT levels were increased, while SOD and GSH-Px were decreased in Mtx group compared with Control-saline group. MDA and ALT levels were increased, while SOD and GSH-Px were decreased in Mtx group, compared with Mtx +Rutin group. Serum AST levels were similar among the groups. CONCLUSION: Rutin may be a potential adjuvant drug to reduce the hepatic side effects observed during Mtx therapy for various clinical conditions.
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Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Imunossupressores/toxicidade , Metotrexato/toxicidade , Rutina/uso terapêutico , Alanina Transaminase/sangue , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Feminino , Glutationa Peroxidase/análise , Fígado/efeitos dos fármacos , Fígado/patologia , Malondialdeído/análise , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Reprodutibilidade dos Testes , Rutina/farmacologia , Superóxido Dismutase/análiseRESUMO
PURPOSE: To investigate the possible protective effect of rutin on methotrexate induced hepatotoxicity in rats. METHODS: Twenty-two rats were divided into three experimental groups; Control-saline, Mtx, Mtx+Rutin. Hepatic tissue was taken for histological assessment and biochemical assays. Oxidative stress parameters malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were investigated. Liver markers aspartate aminotransferase (AST), alanine aminotransferase (ALT) were analyzed in serum. RESULTS: Mtx+Rutin group showed lower histological injury compared to Mtx group, MDA and ALT levels were increased, while SOD and GSH-Px were decreased in Mtx group compared with Control-saline group. MDA and ALT levels were increased, while SOD and GSH-Px were decreased in Mtx group, compared with Mtx +Rutin group. Serum AST levels were similar among the groups. CONCLUSION: Rutin may be a potential adjuvant drug to reduce the hepatic side effects observed during Mtx therapy for various clinical conditions.
Assuntos
Animais , Feminino , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Imunossupressores/toxicidade , Metotrexato/toxicidade , Rutina/uso terapêutico , Alanina Transaminase/sangue , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Glutationa Peroxidase/análise , Fígado/efeitos dos fármacos , Fígado/patologia , Malondialdeído/análise , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Reprodutibilidade dos Testes , Rutina/farmacologia , Superóxido Dismutase/análiseRESUMO
BACKGROUND/AIM: Acetaminophen (APAP) overdose results in severe liver damage that may develop into acute liver failure. Recent studies have demonstrated that inhibition of poly(ADP-ribose) polymerase (PARP) decreases tissue necrosis and inflammation. We evaluated the efficacy of 3-aminobenzamide (3-AB), a PARP inhibitor, in a rodent model of APAP-induced hepatotoxicity. MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were divided equally into 3 experimental groups: sham group, APAP group, and APAP + 3-AB group. In the experimental treatment groups APAP was administered orally at 1 g/kg and, in the APAP + 3-AB group, 3-AB was administered intraperitoneally at a dose of 20 mg/kg exactly 1 h after APAP treatment. Surviving animals were euthanized 48 h after initial APAP administration. Blood samples and liver tissues were collected for histopathological and biochemical analysis. RESULTS: A panel of oxidative stress parameters, as well as serum aspartate aminotransferase, alanine aminotransferase, neopterin, and nitrite/nitrate and histological injury scores, were significantly reduced among the APAP + 3-AB treatment group relative to the group treated with APAP alone (P < 0.05, APAP vs. APAP + 3-AB). CONCLUSION: The present study demonstrates that 3-AB inhibited APAP-induced hepatic injury and reduced neopterin levels. Results of the present study indicate that PARP inhibitors may be an effective adjuvant therapy resulting in improved outcomes in APAP-induced hepatotoxicity.
Assuntos
Benzamidas/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Inibidores Enzimáticos/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases , Substâncias Protetoras/farmacologia , Acetaminofen/toxicidade , Animais , Benzamidas/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/mortalidade , Inibidores Enzimáticos/uso terapêutico , Rim/efeitos dos fármacos , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Neopterina/sangue , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Ratos , Ratos Sprague-Dawley , Análise de SobrevidaRESUMO
OBJECTIVES: Renal involvement is common in sickle cell disease (SCD). Early demonstration of renal injury and commencement of appropriate treatment will increase survival and quality of life in these patients. We investigated renal manifestations in our pediatric and adult SCD patients and evaluated the role of cystatin C, Beta2 microglobulin (B2M), retinol-binding protein (RBP), N-acetyl-beta-D-glucosaminidase (NAG), and endothelin-1 (ET-1) to indicate renal damage. METHODS: The study involved 45 pediatric and 10 adult patients with SCD and 20 healthy children and 10 healthy adults as a control. All the patients were questioned for possible renal manifestations. 24-hour urine samples were collected and glomerular filtration rates (GFRs) were calculated by using creatinine (GFR(creatinine)), Schwartz formula (GFR(Schwartz)), and cystatin C (GFR(cystatin C)). Blood and urine samples were collected and serum cystatin C, urine B2M, RBP, NAG, and ET-1 levels were measured. RESULTS: Nocturnal enuresis and proteinuria were the most common renal manifestations in SCD patients. When the groups were compared in terms of GFR, GFR(creatinine) and GFR(Schwartz) levels were higher in group 1 and 2 patients than in control 1 and 2 patients (P < .05). Cystatin C, B2M, RBP, NAG, and ET-1 values were normal in both the patient and the control groups. However, B2M/creatinine levels were higher than 160 µg/mg creatinine levels in 10 patients. CONCLUSIONS: Serum cystatin C, urine NAG, RBP, and ET-1 levels were found to be insufficient for the evaluation of SCD nephropathy. Increased B2M/creatinie levels can be valuable in estimating possible glomerular and tubular damage in SCD.