Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 601
Int. j. morphol ; 39(2): 407-415, abr. 2021. ilus, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1385337


SUMMARY: Amiodarone (AMD), an orally powerful antidysrhythmic medication that has caused hepatotoxicity on long-term administration, is commonly used across the world. Silymarin ameliorative effects (SLM); this research elucidated the magnitude of the damage to the liver tissue in AMD. We divided 24 albino rats evenly into four groups given daily doses by gastric tube for eight weeks as follows; the 1st group acted as a control group; the 2nd group received SLM; the 3rd group received AMD; and the 4th group received AMD parallel to SLM. Liver tissues prepared for light, electron microscopic and serum samples screened for biomarkers (I)liver injury enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST); (II) oxidative and antioxidant stress, malondialdehyde (MDA) and superoxide dismutase (SOD); and (III) inflammatory markers, tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6). The findings showed that AMD caused hepatic histological changes that included congestion of the blood vessels, leucocytic infiltration and cytoplasmic vacuolation. Ultrastructural degeneration of the mitochondria, endoplasmic reticulum swelling, nuclear pyknosis and increased fat droplets and lysosomes were observed. The biochemical findings showed an increase in the AMD group's ALT and AST activities. The group of rats treated with AMD and SLM, increased the improvements in histology and ultrastructure, while the ALT and AST levels were reduced. Our findings collectively agreed that SLM has a protective impact on AMD hepatotoxicity which can be due to its antioxidant properties.

RESUMEN: La amiodarona (AMD) es un fuerte medicamento antiarrítmico administrado por vía oral que ha causado hepatotoxicidad en la administración a largo plazo utilizado con frecuencia en todo el mundo. Efectos de mejora de la silimarina (SLM); esta investigación analizó la magnitud del daño al tejido hepático en la DMAE. Dividimos 24 ratas albinas de manera uniforme en cuatro grupos que recibieron dosis diarias por sonda gástrica durante ocho semanas de la siguiente manera; el primer grupo fue designado como grupo control; el segundo grupo recibió SLM; el tercer grupo recibió AMD; y el cuarto grupo recibió AMD en paralelo a SLM. Se prepararon tejidos hepáticos para muestras de suero, microscopía de luz y electrónica y se analizaron para biomarcadores (I) enzimas de daño hepático, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST); (II) estrés oxidativo y antioxidante, malondialdehído (MDA) y superóxido dismutasa (SOD); y (III) marcadores inflamatorios, factor de necrosis tumoral alfa (TNF-a) e interleucina-6 (IL-6). Los hallazgos mostraron que la DMAE genera cambios histológicos hepáticos que incluyen congestión de los vasos sanguíneos, infiltración leucocítica y vacuolación citoplásmica. Se observó una degeneración ultraestructural de las mitocondrias, aumento del retículo endoplásmico, picnosis nuclear y aumento de gotitas de grasa y lisosomas. Los hallazgos bioquímicos mostraron un aumento en las actividades de ALT y AST del grupo AMD. El grupo de ratas tratadas con AMD y SLM, aumentó las mejoras en histología y ultraestructura, mientras que se redujeron los niveles de ALT y AST. Nuestros hallazgos coincidieron colectivamente en que SLM tiene un impacto protector sobre la hepatotoxicidad de AMD debido a sus propiedades antioxidantes.

Animals , Female , Rats , Silymarin/administration & dosage , Protective Agents/administration & dosage , Chemical and Drug Induced Liver Injury/drug therapy , Amiodarone/toxicity , Liver/drug effects , Aspartate Aminotransferases/analysis , Rats, Inbred Strains , Silymarin/pharmacology , Superoxide Dismutase , Microscopy, Electron , Interleukin-6 , Tumor Necrosis Factor-alpha , Oxidative Stress , Protective Agents/pharmacology , Alanine Transaminase/analysis , Liver/enzymology , Liver/ultrastructure , Malondialdehyde , Anti-Arrhythmia Agents/toxicity
Mem. Inst. Oswaldo Cruz ; 115: e190364, 2020. tab, graf
Article in English | LILACS | ID: biblio-1091242


Oral transmission of Chagas disease has been increasing in Latin American countries. The present study aimed to investigate changes in hepatic function, coagulation factor levels and parasite load in human acute Chagas disease (ACD) secondary to oral Trypanosoma cruzi transmission. Clinical and epidemiological findings of 102 infected individuals attended in the State of Pará from October 2013 to February 2016 were included. The most common symptoms were fever (98%), asthenia (83.3%), face and limb edema (80.4%), headache (74.5%) and myalgia (72.5%). The hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of 30 ACD patients were higher compared with controls, and this increase was independent of the treatment with benznidazole. Moreover, ACD individuals had higher plasma levels of activated protein C and lower levels of factor VII of the coagulation cascade. Patients with the highest parasite load had also the most increased transaminase levels. Also, ALT and AST were associated moderately (r = 0.429) and strongly (r = 0.595) with parasite load respectively. In conclusion, the present study raises the possibility that a disturbance in coagulation and hepatic function may be linked to human ACD.

Animals , Male , Female , Adult , Aspartate Aminotransferases/blood , Protein C/analysis , Factor VIIa/analysis , Chagas Disease/physiopathology , Alanine Transaminase/blood , Liver/physiopathology , Brazil/epidemiology , Biomarkers/blood , Case-Control Studies , Acute Disease , Prospective Studies , Chagas Disease/enzymology , Chagas Disease/blood , Chagas Disease/transmission , Parasite Load , Liver/enzymology , Middle Aged
Braz. j. infect. dis ; 23(6): 381-387, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1089317


ABSTRACT Setting: Treatment of tuberculosis (TB) can result in Drug-Induced Liver Injury (DILI) since hepatotoxic metabolites are formed during the biotransformation of isoniazid (INH).DILI can be related to the genetic profile of the patient. Single nucleotide polymorphisms in the CYP2E1 gene and GSTM1 and GSTT1 deletion polymorphisms have been associated with adverse events caused by INH. Objective: To characterize the genetic polymorphisms of CYP2E1, GSTT1 and GSTM1 in TB carriers. Design: This is an observational prospective cohort study of 45 patients undergoing treatment of TB. PCR-RFLP and multiplex-PCR were used. Results: The distribution of genotypic frequency in the promoter region (CYP2E1 gene) was: 98% wild genotype and 2% heterozygous. Intronic region: 78% wild genotype; 20% heterozygous and 2% homozygous variant. GST enzyme genes: 24% Null GSTM1 and 22% Null GSTT1. Patients with any variant allele of the CYP2E1 gene were grouped in the statistical analyses. Conclusion: Patients with the CYP2E1 variant genotype or Null GSTT1 showed higher risk of presenting DILI (p = 0.09; OR: 4.57; 95% CI: 0.75-27.6). Individuals with both genotypes had no increased risk compared to individuals with one genotype.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Tuberculosis, Pulmonary/drug therapy , Genetic Predisposition to Disease/genetics , Chemical and Drug Induced Liver Injury/genetics , Antitubercular Agents/adverse effects , Polymorphism, Genetic , Tuberculosis, Pulmonary/enzymology , Prospective Studies , Cytochrome P-450 CYP2E1 , Cytochrome P-450 Enzyme System/genetics , Chemical and Drug Induced Liver Injury/enzymology , Cytochrome P450 Family 2 , Genotype , Liver/drug effects , Liver/enzymology , Antitubercular Agents/therapeutic use
Acta cir. bras ; 33(11): 954-963, Nov. 2018. tab, graf
Article in English | LILACS | ID: biblio-973477


Abstract Purpose: The effect of a prophylactic oleuropein-rich diet before anesthesia accompanied by the widely-used steroid-based neuromuscular drug rocuronium on mast cell activation was investigated in the study. Methods: 14 rabbits used in the study. The rabbits in the oleuropein group were given oleuropein-rich extract added to the animals' water at doses of 20 mg/kg oleuropein for 15 days orally. After 15 days, all rabbits in the two groups were given general anesthesia with rocuronium of 1 mg/kg. After 1 day, animals were sacrificed and the liver tissue sections stained with H&E, toluidine blue and tryptase for immunohistochemical study. Results: There was no statistically significant difference between ALT, AST and albumin averages of the oleuropein and control groups (p> 0.05). The tryptase average of the control group was higher than the tryptase average of the oleuropein group and this difference was statistically significant (p=0.003). The T. blue average in the oleuropein group was higher than the control group. However, there was no statistically significant difference between groups (p=0.482). Conclusions: Rocuronium adverse effects, like hypersensitivity and anaphylaxis, may limit routine use of this substance. The use of oleuropein reduced the number of inflammatory cells and prevented degranulation.

Animals , Male , Rabbits , Neuromuscular Nondepolarizing Agents/adverse effects , Iridoids/administration & dosage , Rocuronium/adverse effects , Anesthesia, General/adverse effects , Mast Cells/drug effects , Anti-Inflammatory Agents/administration & dosage , Aspartate Aminotransferases/blood , Serum Albumin/analysis , Random Allocation , Cell Degranulation/drug effects , Cell Aggregation/drug effects , Reproducibility of Results , Chromatography, High Pressure Liquid , Diet Therapy/methods , Alanine Transaminase/blood , Drug-Related Side Effects and Adverse Reactions/prevention & control , Pre-Exposure Prophylaxis/methods , Liver/drug effects , Liver/enzymology , Mast Cells/pathology
Braz. j. biol ; 78(2): 281-288, May-Aug. 2018. tab, graf
Article in English | LILACS | ID: biblio-888879


Abstract Knowledge of specific enzyme activity, along with animal habits and digestive capacity is essential in formulating an appropriate diet for any species. In this study, we evaluated and characterized the activity of digestive enzymes present in the liver, intestine, and stomach of Paralichthys orbignyanus. The effects of pH and temperature on enzyme activity were also evaluated via the use of specific substrates. The use of specific substrates and inhibitors showed strong evidence of the presence of trypsin (BApNA= 0.51 ± 0.2 mU mg-1), chimotrypsin (SApNA= 2.62 ± 1.8 mU mg-1), and aminopeptidases (Leu-p-Nan =0.9709 ± 0.83 mU mg-1) in the intestine. Optimum pH for the activity of trypsin, chemotrypsin, leucino aminopeptidase, amilase, and pepsin were 9.5, 9.0, 8.0, 7.5, and 3.5, respectively, while optimum temperatures were 50, 50, 50, 40, and 45 °C, respectively. These results provide additional information regarding the biology of Brazilian flounder and can be used as a basis for further studies regarding fish feeding physiology.

Resumo O conhecimento da atividade enzimática é essencial para formular uma correta dieta específica para espécie, além de estarem correlacionadas com o hábito da alimentação e capacidade digestive. Neste estudo determinamos e caracterizamos a atividade enzimática presente no intestino, estômago e fígado do linguado Paralichthys orbignyanus. Os efeitos da temperatura e pH sobre a atividade enzimática também foram avaliados utilizando substratos específicos. O uso de substratos e inibidores específicos mostrou uma forte evidência da presença da tripsina (BApNA = 0,51 ± 0,2 mU mg-1), quimotripsina (SAPNA = 2,62 ± 1,8 mU mg-1), e as aminopeptidases (Leu-p-Nan = 0,97 ± 0,83 mU mg-1) no intestino. O pH ótimo observado para a atividade de tripsina, quimotripsina, leucino aminopeptidase, amilase e pepsina foi 9,5, 9,0, 8,0, 7,5 e 3,5, respectivamente. A temperatura ótima observada foi 50, 50, 50, 40 e 45 °C, respectivamente. Estes resultados fornecem informações adicionais sobre a biologia do linguado brasileiro e pode ser usado como base para novos estudos sobre fisiologia alimentar.

Animals , Flounder/physiology , Fish Proteins/metabolism , Fish Proteins/chemistry , Gastrointestinal Tract/enzymology , Aminopeptidases/metabolism , Aminopeptidases/chemistry , Temperature , Enzyme Stability , Brazil , Serine Endopeptidases/metabolism , Serine Endopeptidases/chemistry , Hydrogen-Ion Concentration , Liver/enzymology
Acta cir. bras ; 33(5): 439-445, May 2018. graf
Article in English | LILACS | ID: biblio-949344


Abstract Purpose: To investigate the effects of capsiate treatment on hepatic hyperplasia in partially hepatectomized rats. Methods: The animals were divided into a Capsiate group (CPH), a Capsiate Post-Partial Hepatectomy group (CPPH) and a Partial Hepatectomy Control group (PH). CPH and CPPH animals received 60 mg/kg/day Capsiate for 30 days. Next, the rats underwent partial hepatectomy. CPPH animals continued to receive treatment for 48 h after partial hepatectomy. Liver tissue and intracardiac blood samples were obtained 24 or 48 h after PH. Results: Capsiate treatment interfered with hepatic parameters, reducing the number of mitoses and apoptosis and increasing blood ALT and alkaline phosphatase concentrations. Conclusion: Capsiate treatment preceding hepatic surgery may compromise the initial period of postoperative recovery.

Animals , Male , Rats , Capsaicin/analogs & derivatives , Hepatectomy , Liver/enzymology , Aspartate Aminotransferases/metabolism , Capsaicin/pharmacology , Rats, Wistar , Apoptosis/drug effects , Alanine Transaminase/metabolism , Alkaline Phosphatase/metabolism , Liver/drug effects , Liver/pathology , Liver Regeneration/drug effects , Mitosis/drug effects
Braz. j. med. biol. res ; 51(4): e6980, 2018. graf
Article in English | LILACS | ID: biblio-889067


Hormones regulate hepatic gene expressions to maintain metabolic homeostasis. Ectonucleotide pyrophosphatase/phosphodiesterase 1 has been thought to interfere with insulin signaling. To determine its potential role in the regulation of metabolism, we analyzed its gene (Enpp1) expression in the liver of rats experiencing fasting and refeeding cycles, and in primary rat hepatocytes and human hepatoma HepG2 cells treated with insulin and dexamethasone using northern blot and real-time PCR techniques. Hepatic Enpp1 expression was induced by fasting and reduced by refeeding in the rat liver. In primary rat hepatocytes and HepG2 hepatoma cells, insulin reduced Enpp1 mRNA abundance, whereas dexamethasone induced it. Dexamethasone disrupted the insulin-reduced Enpp1 expression in primary hepatocytes. This is in contrast to the responses of the expression of the cytosolic form of phosphoenolpyruvate carboxykinase gene to the same hormones, where insulin reduced it significantly in the process. In addition, the dexamethasone-induced Enpp1 gene expression was attenuated in the presence of 8-Br-cAMP. In conclusion, we demonstrated for the first time that hepatic Enpp1 is regulated in the cycle of fasting and refeeding, a process that might be attributed to insulin-reduced Enpp1 expression. This insulin-reduced Enpp1 expression might play a role in the development of complications in diabetic patients.

Humans , Animals , Male , Rats , Pyrophosphatases/genetics , RNA, Messenger/drug effects , Dexamethasone/pharmacology , Phosphoric Diester Hydrolases/genetics , Glucocorticoids/pharmacology , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Liver/enzymology , Pyrophosphatases/biosynthesis , Pyrophosphatases/drug effects , Insulin Resistance , RNA, Messenger/metabolism , Gene Expression Regulation, Enzymologic/drug effects , Enzyme Induction/drug effects , Fasting/metabolism , Rats, Sprague-Dawley , Phosphoric Diester Hydrolases/biosynthesis , Phosphoric Diester Hydrolases/drug effects , Hep G2 Cells , Real-Time Polymerase Chain Reaction
Acta cir. bras ; 32(8): 633-640, Aug. 2017. graf
Article in English | LILACS | ID: biblio-886223


Abstract Purpose: To evaluate the effect of hyperin in cisplatin-induced liver injury in mice. Methods: Mice were pretreated with hyperin at doses of 25 mg/kg and 50 mg/kg, respectively, for six days, and intraperitoneal injection of cisplatin (40 mg/kg) was administrated one hour after the final intragastrication of hyperin. Twenty-four hours later, blood and liver were collected for further research. Results: A single injection of cisplatin (40 mg/kg) for 24 h significantly increased serum alanine and aspartate aminotransferases (ALT/AST) and gamma glutamyl transferase (GGT) activities, whileas hyperin reversed cisplatin-induced such increases. Liver histopathological examination further demonstrated the protection of hyperin against cisplatin-induced liver injury. Further results showed hyperin reversed cisplatin-induced the increase in content of malondialdehyde (MDA) and the decrease in level of total antioxidant capacity (T-AOC) in liver. Moreover, hyperin increased the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione-s transferase (GST) in cisplatin-induced liver. Conclusion: Hyperin inhibits cisplatin-induced hepatic oxidative stress, which contributes greatly to the amelioration of cisplatin-induced liver injury in mice.

Animals , Male , Quercetin/analogs & derivatives , Aspartate Aminotransferases/metabolism , Cisplatin/adverse effects , Chemical and Drug Induced Liver Injury/prevention & control , Antineoplastic Agents/adverse effects , Antioxidants/pharmacology , Quercetin/therapeutic use , Quercetin/pharmacology , Reference Values , Lipid Peroxidation , Catalase/analysis , Random Allocation , Reproducibility of Results , Cisplatin/antagonists & inhibitors , Oxidative Stress/drug effects , Alanine Transaminase/metabolism , Chemical and Drug Induced Liver Injury/pathology , Glutathione/analysis , Glutathione Peroxidase/analysis , Glutathione Transferase/analysis , Liver/drug effects , Liver/enzymology , Liver/pathology , Malondialdehyde/analysis , Mice, Inbred ICR , Antioxidants/therapeutic use
Acta cir. bras ; 32(3): 194-202, Mar. 2017. tab, graf
Article in English | LILACS | ID: biblio-837694


Abstract Purpose: To investigate the effects of lycopene and resveratrol pretreatment on hepatic hyperplasia in partially hepatectomized rats. Methods: The lycopene group and the resveratrol group received 40 mg/kg/day of lycopene or resveratrol, respectively (dissolved in olive oil or in saline solution, respectively) and administered via a gastric tube for 30 days. The partially hepatectomzed (PH) control groups received saline or olive oil via a gastric tube for 30 days, respectively, and the normal control group received no treatment. Liver tissue and intracardiac blood samples were obtained 24, 36 or 48 h after PH. Results: No areas of fibrosis were detected. No significant changes in mitotic index, in the number of apoptosis events or in aspartate aminotransferase and alanine aminotransferase levels were observed. Conclusions: Lycopene and resveratrol pretreatment did not interfere on hepatic hyperplasia in partially hepatectomized rats.

Animals , Male , Stilbenes/pharmacology , Carotenoids/pharmacology , Hepatectomy/methods , Liver/surgery , Liver/drug effects , Antioxidants/pharmacology , Aspartate Aminotransferases/blood , Time Factors , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Apoptosis/drug effects , Oxidative Stress/drug effects , Alanine Transaminase/blood , Liver/enzymology , Liver/pathology , Liver Regeneration/drug effects , Mitotic Index
Mem. Inst. Oswaldo Cruz ; 112(2): 146-154, Feb. 2017. graf
Article in English | LILACS | ID: biblio-841766


BACKGROUND Leishmaniasis is a parasitosis caused by several species of the genus Leishmania. These parasites present high resistance against oxidative stress generated by inflammatory cells. OBJECTIVES To investigate oxidative stress and molecular inflammatory markers in BALB/c mice infected with L. amazonensis and the effect of antioxidant treatment on these parameters. METHODS Four months after infection, oxidative and inflammatory parameters of liver, kidneys, spleen, heart and lungs from BALB/c mice were assessed. FINDINGS In liver, L. amazonensis caused thiol oxidation and nitrotyrosine formation; SOD activity and SOD2 protein content were increased while SOD1 protein content decreased. The content of the cytokines IL-1β, IL-6, TNF-α, and the receptor of advanced glycation endproducts (RAGE) increased in liver. Treatment with the antioxidant N-acetyl-cysteine (20 mg/kg b.w) for five days inhibited oxidative stress parameters. MAIN CONCLUSIONS L. amazonensis induces significant alterations in the redox status of liver but not in other organs. Acute antioxidant treatment alleviates oxidative stress in liver, but it had no effect on pro-inflammatory markers. These results indicate that the pathobiology of leishmaniasis is not restricted to the cutaneous manifestations and open perspectives for the development of new therapeutic approaches to the disease, especially for liver function.

Animals , Mice , Acetylcysteine/pharmacology , Leishmania mexicana , Leishmaniasis, Cutaneous/metabolism , Leishmaniasis, Cutaneous/pathology , Oxidative Stress/drug effects , Oxidative Stress/physiology , Free Radical Scavengers/pharmacology , Liver/drug effects , Liver/enzymology , Mice, Inbred BALB C
Rev. Soc. Bras. Med. Trop ; 49(6): 693-697, Dec. 2016. tab, graf
Article in English | LILACS | ID: biblio-829668


Abstract: INTRODUCTION: Dengue fever is a viral disease transmitted by the Aedes aegypti Linn. (1792) (Diptera: Culicidae) mosquito, which is endemic in several regions of Brazil. Alternative methods for the control of the vector include botanical insecticides, which offer advantages such as lower environmental contamination levels and less likelihood of resistant populations. Thus, in this study, the ability of botanical insecticide formulations to inhibit the activity of the liver enzymes serum cholinesterase and malate dehydrogenase was evaluated. METHODS: Inhibition profiles were assessed using in vitro assays for cholinesterase and malate dehydrogenase activity and quantitated by ultraviolet-visible spectroscopy at 410nm to 340nm. RESULTS Insecticide products formulated from cashew nutshell liquid [A] and ricinoleic acid [B] showed cholinesterase activity levels of 6.26IU/mL and 6.61IU/mL, respectively, while the control level for cholinesterase was 5-12IU/mL. The products did not affect the level of 0.44IU/mL established for malate dehydrogenase, as the levels produced by [A] and [B] were 0.43IU/mL and 0.45IU/mL, respectively. CONCLUSIONS Our findings show that in vitro testing of the formulated products at concentrations lethal to A. aegypti did not affect the activity of cholinesterase and malate dehydrogenase, indicating the safety of these products.

Humans , Animals , Ricinoleic Acids/pharmacology , Cholinesterase Inhibitors/pharmacology , Cholinesterases/drug effects , Anacardium/chemistry , Insecticides/pharmacology , Liver/enzymology , Malate Dehydrogenase/antagonists & inhibitors , Spectrophotometry, Ultraviolet , In Vitro Techniques , Ricinoleic Acids/isolation & purification , Aedes , Insect Vectors/drug effects , Insecticides/isolation & purification
Acta cir. bras ; 31(3): 168-175, Mar. 2016. graf
Article in English | LILACS | ID: lil-777089


ABSTRACT PURPOSE : To investigate the effects of thiamine pyrophosphate (TPP) against desflurane induced hepatotoxicity. METHODS : Thirty experimental animals were divided into groups as healthy (HG), desflurane control (DCG) , TPP and desflurane group (TDG). 20 mg/kg TPP was injected to intraperitoneally TDG. After one hour of TPP administration, desflurane was applied for two hours. After 24 hours, liver tissues of the animals killed with decapitation were removed. The oxidant/antioxidant levels and ALT, AST and LDH activities were measured. The histopathological examinations were performed in the liver tissues for all rats. RESULTS : Notwithstanding the levels of oxidants and liver enzymes were significantly increased (p<0.0001), antioxidant levels were significantly decreased in DCG (p<0.0001). On contrary to the antioxidant parameters were increased (p<0.05) the oxidant parameters and liver enzymes were decreased in TDG (p<0.0001). Whereas multiple prominent, congestion, hemorrhage and dilatation were observed in sinusoids and lymphocyte-rich inflammation results in the centrilobular and portal areas of liver tissue in DCG, these findings were observed less frequently in TDG. CONCLUSİON : Thiamine pyrophosphate prevented liver oxidative damage induced with desflurane and may be useful in prophylaxis of desflurane induced hepatotoxicity.

Animals , Male , Thiamine Pyrophosphate/therapeutic use , Anesthetics, Inhalation/adverse effects , Protective Agents/pharmacology , Chemical and Drug Induced Liver Injury/prevention & control , Isoflurane/analogs & derivatives , Aspartate Aminotransferases/drug effects , Aspartate Aminotransferases/metabolism , Rats, Wistar , Peroxidase/drug effects , Oxidative Stress/drug effects , Alanine Transaminase/drug effects , Alanine Transaminase/metabolism , Chemical and Drug Induced Liver Injury/metabolism , Glutathione/drug effects , Glutathione/metabolism , Isoflurane , L-Lactate Dehydrogenase/drug effects , L-Lactate Dehydrogenase/metabolism , Liver/enzymology , Liver/pathology , Malondialdehyde/metabolism , Nitric Oxide/metabolism
Braz. j. med. biol. res ; 49(11): e5238, 2016. graf
Article in English | LILACS | ID: lil-797893


Early nutrition plays a long-term role in the predisposition to chronic diseases and influences the metabolism of several drugs. This may happen through cytochromes P450 (CYPs) regulation, which are the main enzymes responsible for the metabolism of xenobiotics. Here, we analyzed the effects of maternal protein restriction (MPR) on the expression and activity of hepatic offspring’s CYPs during 90 days after birth, using Wistar rats as a mammal model. Hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2 and CYP2E1 mRNA and protein expression, and associated catalytic activities (ECOD, EROD, MROD, BROD, PROD and PNPH) were evaluated in 15-, 30-, 60-, and 90-day-old offspring from dams fed with either a 0% protein (MPR groups) or a standard diet (C groups) during the 10 first days of lactation. Results showed that most CYP genes were induced in 60- and 90-day-old MPR offspring. The inductions detected in MPR60 and MPR90 were of 5.0- and 2.0-fold (CYP1A2), 3.7- and 2.0-fold (CYP2B2) and 9.8- and 5.8– fold (CYP2E1), respectively, and a 3.8-fold increase of CYP2B1 in MPR90. No major alterations were detected in CYP protein expression. The most relevant CYP catalytic activities’ alterations were observed in EROD, BROD and PNPH. Nevertheless, they did not follow the same pattern observed for mRNA expression, except for an induction of EROD in MPR90 (3.5-fold) and of PNPH in MPR60 (2.2-fold). Together, these results suggest that MPR during lactation was capable of altering the expression and activity of the hepatic CYP enzymes evaluated in the offspring along development.

Animals , Female , Rats , Cytochrome P-450 Enzyme System/metabolism , Diet, Protein-Restricted , Lactation/metabolism , Liver/enzymology , Aryl Hydrocarbon Hydroxylases/metabolism , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP1A2/metabolism , Cytochrome P-450 CYP2B1/metabolism , Cytochrome P-450 CYP2E1/metabolism , Models, Animal , Rats, Wistar , Steroid Hydroxylases/metabolism , Time Factors
Rio de Janeiro; s.n; 2016. 68 p. ilus, tab.
Thesis in Portuguese | LILACS | ID: biblio-983468


É conhecido que processos inflamatórios podem modular a expressão e atividade deenzimas CYPs. Não é claro, entretanto, o modo pelo qual estímulos inflamatórios regulam aexpressão dessas enzimas. Neste trabalho investigamos a hipótese de que as células deKupffer do fígado exerceriam um papel na modulação dos CYPs hepáticos em resposta àinflamação exacerbada ou sepse. O cloreto de gadolínio, é um inibidor seletivo das células deKupffer, conhecido por atenuar o quadro de inflamação exacerbada, quandoadministradopreviamente ao estímulo inflamatório, em diferentes modelos animais. Algunsautores sugeriram que as células de Kupffer atuariam como intermediários na modulação daatividade de CYPs hepáticos desencadeada por estímulos inflamatórios. Há estudos quesugerem que a diminuição da população das células de Kupfferatenua ou elimina a regulaçãodas CYPs hepáticas por estímulos inflamatórios.Além disso, estudos em culturas dehepatócitos in vitro, na ausência de células de Kupffer, tem constatado a regulação negativa daexpressão de CYPs hepáticas após estimulação com LPS. Nessa linha, o objetivo destepresente trabalho é investigar o papel das células de Kupffer na regulação da atividade deenzimas hepáticas de biotransformação de xenobióticos (CYPs) após estimulação inflamatóriacom LPS. Para isso, os níveis séricos de transaminases, e a histopatologia foram empregadospara avaliar o efeito do tratamento com diferentes doses de GdCl3sobre o tecido hepático.Noexperimento principal para investigar o papel das células de Kupffer, os ratos foram alocadosao acaso em quatro grupos. Foram quantificadosmarcadores bioquímicos no soro dos animaispara evidenciar danos ao tecido hepático causados pelos tratamentos e realizado o examehistopatológico...

It is known that inflammatory processes may modulate the expression and activity ofCYP enzymes. The mode by which inflammatory stimuli regulate CYP expression andactivity, however, remains unclear. Kupffer cells are resident macrophages in the liver andthus play an important role in a systemic inflammatory process or in sepsis. Gadoliniumchloride (GdCl3) has been reported to selectively kill an/or inhibit the activity of Kupffercells. Along this line, it has also been described that Gd decreases exacerbated inflammatoryresponses when it is administered prior to inflammatory stimuli in various animal models.Therole of Kupffer cells in the modulation of CYPs activity triggered by inflammatory stimuli,however, is not entirely clear in the literature. There are studies suggesting that a reduction inthe population of Kupffer cells attenuates the down-regulation of hepatic CYPs induced byinflammatory stimuli. However, GdCl3 was also described to decrease liver CYP activityirrespective of whether it depletes or not Kupffer cells. Moreover, in vitro studies showed thatLPS down-regulates the expression of CYP forms in hepatocyte cell lines in culture (in theabsence of Kupffer cells). To investigate whether Kupffer cells play a role in the regulation ofthe activity of liver xenobiotic biotransformation enzymes (CYPs) by inflammatorystimulation with LPS. The activity of transaminases in the blood serum (a marker for liverinjury) was determined and liver histopathology was evaluated in female Wistar rats. In a setof preliminary tests, rats were treated with different doses of GdCl3 or with LPS for selectingdoses and euthanasia time in the main experiment. In the main study experimental groups.Treatment associated liver injury was evaluated by levels of transaminases and alkalinephosphatase in the blood serum and by liver histopathology examination...

Animals , Mice , Kupffer Cells/enzymology , Liver/enzymology , Xenobiotics/metabolism , Endotoxins , Euthanasia , Gadolinium
Article in English | WPRIM | ID: wpr-56139


Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease characterized by hepatocellular inflammation, necrosis, and fibrosis, which can progress to cirrhosis and fulminant hepatic failure. The standard treatment for AIH includes corticosteroids alone or in combination with azathioprine. Although most patients achieve remission using the standard regimen, some patients do not respond due to either drug intolerance or refractory disease; in such cases alternative immunosuppressive agents should be explored. The second-line therapies are cyclophilin inhibitors such as cyclosporine A or tacrolimus, and nowadays mycophenolate mofetil (MMF) is widely used if azathioprine-based therapies are not tolerated. Although these are recommended as an alternative to the first-line regimen, there is insufficient evidence for the efficacy of second-line therapies, with the evidence based mainly on expert opinion. Therefore, we report an AIH patient receiving the standard regimen in whom remission did not occur due to side effects to azathioprine, but was successfully treated with MMF in combination with corticosteroids as an alternative to the standard regimen.

Female , Humans , Middle Aged , Alanine Transaminase/analysis , Alopecia/etiology , Antibiotics, Antineoplastic/therapeutic use , Aspartate Aminotransferases/analysis , Azathioprine/adverse effects , Hepatitis, Autoimmune/drug therapy , Liver/enzymology , Mycophenolic Acid/therapeutic use , Pancytopenia/etiology , Prednisolone/therapeutic use
Pesqui. vet. bras ; 35(9): 781-787, Sept. 2015. tab, graf
Article in English | LILACS | ID: lil-767741


Infection with Escherichia coli (E. coli) is a common disease in poultry industry. The use of antibiotics to treat diseases is facing serious criticism and concerns. The medicinal plants may be effective alternatives because of their multiplex activities. The aim of this study was to investigate the effects of cinnamon extract on the levels of liver enzymes, tumor necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-κB) gene expressions in liver of broiler chickens infected with E. coli. Ninety Ross-308 broilers were divided into healthy or E. coli-infected groups, receiving normal or cinnamon extract (in concentrations of 100 or 200mg/kg of food) supplemented diets. E. coli suspension (108cfu) was injected subcutaneously after 12 days cinnamon administration. Seventy-two hours after E. coli injection, the blood samples were taken for biochemical analysis of liver enzymes in serum (spectrophotometrically), and liver tissue samples were obtained for detection of gene expression of inflammatory markers TNF-α and NF-κB, using real-time PCR. Infection with E. coli significantly increased the levels of TNF-α and NF-κB gene expressions as well as some liver enzymes including creatine-kinase (CK), lactate-dehydrogenase (LDH), alanine-transferase (ALT) and aspartate-transferase (AST) as compared with control group (P<0.05). Pre-administration of cinnamon extract in broilers diet (in both concentrations) significantly reduced the tissue levels of TNF-α and NF-κB gene expressions and enzymes CK and ALT in serum of broiler chickens inoculated with E. coli in comparison with E. coli group (P<0.05 and P<0.01). The levels of LDH and AST were significantly decreased only by 200mg/kg cinnamon extract in infected broilers. The level of alkaline-phosphatase (ALP) was not affected in any groups. Pre-administration of cinnamon extract in diets of broiler chickens inoculated with E. coli could significantly reduce the gene expression levels...

Infecção ocasionada por Escherichia coli (E. coli) é uma enfermidade comum na indústria avícola. O uso de antibióticos para tratar doenças bacterianas vem enfrentando sérias críticas e preocupações. As plantas medicinais podem ser alternativas eficazes por causa de suas atividades sinérgicas. O objetivo deste estudo foi investigar os efeitos do extrato de canela sobre os níveis de as enzimas hepáticas bem como sobre a expressão dos genes relativos, fator de necrose tumoral-alfa (TNF-α) e fator nuclear -kappa B (NF-κB) em fígado de frangos de corte infectados com E. coli. Noventa frangos Ross-308 foram divididos em grupos saudáveis ou infectados com E. coli, que receberam dietas controle ou com suplementação contendo extrato de canela (em concentrações de 100 ou 200 mg/kg de alimento). Suspensão de E. coli (108UFC) foi injetado por via subcutânea, após 12 dias de administração do extrato de canela. Setenta e duas horas após a injeção de E. coli, amostras de sangue foram colhidas para análise bioquímica das enzimas do fígado no soro (espectrofotometria), e amostras de tecido de fígado foram obtidas para a determinação da expressão de genes de marcadores inflamatórios TNF-α e NF-κB, através PCR em tempo real. A infecção com E. coli aumentou significativamente os níveis de expressão dos genes TNF-α e NF-κB, assim como algumas enzimas hepáticas, incluindo creatina-quinase (CK), lactato-desidrogenase (LDH), alanina-transferase (ALT) e aspartato-transferase (AST), em comparação com o grupo de controle (P<0.05). A pré-administração do extrato de canela na dieta dos frangos (em ambas as concentrações) reduziu significativamente os níveis de expressão tecidual de TNF-α e NF-kB, da mesma forma que das enzimas CK e ALT no soro de frangos infectados com E. coli, em comparação com o grupos somente infectado com E. coli (P<0.05 e P<0.01). Os níveis de LDH e AST foram significativamente menores apenas para o grupo suplementado com extrato de canela na concentração...

Animals , Cinnamomum zeylanicum , Escherichia coli/pathogenicity , Tumor Necrosis Factor-alpha , Galliformes/microbiology , NF-kappa B , Alanine Transaminase , Aspartate Aminotransferases , Creatine Kinase , Liver/enzymology , Alkaline Phosphatase , L-Lactate Dehydrogenase , Plants, Medicinal , Real-Time Polymerase Chain Reaction/veterinary
Clinics ; 70(5): 350-355, 05/2015. tab, graf
Article in English | LILACS | ID: lil-748270


OBJECTIVE: Sacrococcygeal pilonidal sinus is common in young men and may recur over time after surgery. We investigated whether a factor exists that can aid in the determination of the preferred technique between the early Limberg flap and Karydakis flap techniques for treating recurrent pilonidal sinus. MATERIALS AND METHODS: This prospective and randomized study enrolled 71 patients with recurrent pilonidal sinus in whom the Limberg flap or Karydakis flap techniques were applied for reconstruction after excision. Patients were divided into two groups as follows: 37 patients were treated with the Limberg flap technique and 34 patients were treated with the Karydakis flap technique. Fluid collection, wound infection, flap edema, hematoma, partial wound separation, return to daily activities, pain score, complete healing time, painless seating and patient satisfaction were compared between the groups. NCT02287935. RESULTS: The development rates of total fluid collection, wound infection, flap edema, hematoma, and partial wound separation were 9.8%, 16%, 7%, 15% and 4.2%, respectively; total flap necrosis was not observed in any patient (p<0.001). During the average follow-up of 28 months, no patients (0%) developed recurrent disease. The two groups differed with respect to early surgical complications (p<0.001). CONCLUSION: In this study, use of the Limberg flap was associated with lower complication rates, shorter length of hospital stay, early return to work, low pain score, high patient satisfaction and better complete healing duration. Therefore, we recommend the Limberg flap for treatment of recurrent pilonidal sinus. .

Animals , Male , Rats , Aryldialkylphosphatase/genetics , Environmental Pollutants/toxicity , Gene Expression Regulation, Enzymologic/drug effects , Liver/drug effects , Polychlorinated Biphenyls/toxicity , Antioxidants/metabolism , Aryldialkylphosphatase/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Dose-Response Relationship, Drug , Lipid Peroxidation/drug effects , Liver/enzymology , Malondialdehyde/metabolism , Rats, Sprague-Dawley , Thiobarbituric Acid Reactive Substances/metabolism
J. bras. pneumol ; 41(2): 151-160, Mar-Apr/2015. tab, graf
Article in English | LILACS | ID: lil-745914


OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD). METHODS: This was a retrospective study of patients with interstitial lung disease (ILD), positive antinuclear antibody (ANA) results (≥ 1/320), with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD). RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89%) and anti-SSA (anti-Ro, 27%). The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05). Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria. .

OBJETIVO: Descrever as características de uma coorte de pacientes com colagenose pulmão dominante (CPD). MÉTODOS: Estudo retrospectivo de pacientes com doença pulmonar intersticial (DPI), anticorpo antinuclear (ANA) positivo (≥ 1/320), com ou sem autoanticorpos específicos, e com a presença de ao menos uma manifestação clínica sugestiva de doença do tecido conjuntivo (DTC). RESULTADOS: Dos 1.998 avaliados, 52 preencheram inicialmente os critérios para o diagnóstico de CPD: 37% eram homens; a média de idade ao diagnóstico era de 56 anos e a mediana do tempo de seguimento era de 48 meses. Durante o seguimento, 8 pacientes preencheram os critérios para um diagnóstico definitivo de DTC. Os 44 pacientes restantes formaram o grupo CPD, no qual as manifestações extratorácicas mais prevalentes foram artralgia, doença do refluxo gastroesofágico e fenômeno de Raynaud. Os autoanticorpos mais prevalentes nesse grupo foram ANA (89%) e anti-SSA (anti-Ro, 27%). A média de CVF no início e na última avaliação foi de 69,5% e 74,0% do predito, respectivamente (p > 0,05). Pneumonia intersticial não específica e pneumonia intersticial usual foram identificadas em 45% e 9% das TCARs, respectivamente; 36% das TCARs eram não classificáveis. Uma prevalência semelhante foi identificada na histologia. Dilatação esofágica difusa foi identificada em 52% das TCARs. Capilaroscopia subungueal foi realizada em 22 pacientes; 17 apresentavam um padrão de esclerodermia. CONCLUSÕES: No grupo CPD, houve predominância feminina, e os pacientes apresentaram alterações espirométricas leves ao diagnóstico, com diferentes padrões de DPI, em sua maioria não classificáveis, tanto em TCAR como na histologia. Estabilidade funcional foi identificada no seguimento. A dilatação esofágica em TCAR e o padrão de esclerodermia na capilaroscopia subungueal foram achados frequentes que poderiam servir como critérios diagnósticos. .

Adult , Humans , Middle Aged , Fatty Liver/metabolism , Hydrocortisone/metabolism , Liver/metabolism , /genetics , /metabolism , Case-Control Studies , Disease Progression , Fatty Liver/complications , Fatty Liver/enzymology , Fatty Liver/urine , Gene Expression Regulation, Enzymologic , Hydrocortisone/urine , Liver/enzymology , Liver/pathology , Models, Biological , Non-alcoholic Fatty Liver Disease , Obesity/complications , Obesity/urine , Real-Time Polymerase Chain Reaction , RNA, Messenger/genetics , RNA, Messenger/metabolism
Rev. paul. pediatr ; 33(1): 63-71, Jan-Mar/2015. tab
Article in English | LILACS | ID: lil-744703


OBJECTIVE : To verify the correlation between body fat location measurements with the body mass index (BMI), body fat percentage (BF%) and height, according to the nutritional status in female adolescents. METHODS : A controlled cross-sectional study was carried out with 113 adolescents (G1: 38 with normal weight, but with high body fat level, G2: 40 with normal weight and G3: 35 overweight) from public schools in Viçosa-MG, Brazil. The following measures were assessed: weight, height, waist circumference (WC), umbilical circumference (UC), hip circumference (HC), thigh circumference, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), waist-to-thigh ratio (WTR), conicity index (CI), sagittal abdominal diameter (SAD), coronal diameter (CD), central (CS) and peripheral skinfolds (PS). The BF% was assessed by tetrapolar electric bioimpedance. RESULTS : The increase in central fat, represented by WC, UC, WHtR, SAD, CD and CS, and the increase in peripheral fat indicated by HC and thigh circumference were proportional to the increase in BMI and BF%. WC and especially the UC showed the strongest correlations with adiposity. Weak correlation between WHR, WTR, CI and CS/PS with adiposity were observed. The height showed correlation with almost all the fat location measures, being fair or weak with waist measurements. CONCLUSIONS : The results indicate colinearity between body mass and total adiposity with central and peripheral adipose tissue. We recommend the use of UC for assessing nutritional status of adolescents, as it showed the highest capacity to predict adiposity in each group, and also showed fair or weak correlation with height. .

OBJETIVO: Verificar a correlação entre medidas de localização da gordura corporal com índice de massa corporal (IMC), percentual de gordura corporal (%GC) e estatura, de acordo com o estado nutricional em adolescentes do sexo feminino. MÉTODOS: Realizou-se estudo transversal controlado, com 113 adolescentes (G1: 38 eutróficas mas com gordura corporal elevada; G2: 40 eutróficas e G3: 35 com excesso de peso), de 14 a 19 anos, de escolas públicas de Viçosa-MG. Aferiu-se peso, estatura, circunferência da cintura (CC), circunferência umbilical (CUm), circunferência do quadril (CQ), circunferência da coxa, relação cintura/quadril (RCQ), relação cintura/estatura (RCE), relação cintura/coxa (RCC), índice de conicidade (IC), diâmetro abdominal sagital (DAS), diâmetro coronal (DC), pregas cutâneas centrais (PCC) e periféricas (PCP). Avaliou-se o %GC por bioimpedância elétrica tetrapolar. RESULTADOS: O aumento da gordura central, representada pela CC, CUm, RCE, DAS, DC e PCC, e o aumento da gordura periférica indicado pela CQ e da coxa foram proporcionais ao aumento do IMC e %GC. A CC e principalmente CUm apresentaram as correlações mais fortes com a adiposidade, enquanto RCQ, RCC, IC e PCC/PCP as mais fracas. A estatura apresentou correlação com praticamente todas as medidas de localização de gordura, sendo de fraca a regular com as medidas da cintura. CONCLUSÕES: Os resultados indicam colinearidade entre massa corporal e adiposidade total com tecido adiposo central e periférico. Recomenda-se o emprego da CUm na avaliação do estado nutricional de adolescentes, pois ela apresentou maior capacidade para predizer adiposidade em cada grupo, além de correlação fraca a regular com a estatura. .

Animals , Rats , Drug Design , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/metabolism , Hydroxamic Acids/pharmacology , Dose-Response Relationship, Drug , Histone Deacetylase Inhibitors/chemistry , Histone Deacetylase Inhibitors/chemical synthesis , Hydroxamic Acids/chemistry , Hydroxamic Acids/chemical synthesis , Liver/enzymology , Molecular Structure , Structure-Activity Relationship
Mem. Inst. Oswaldo Cruz ; 110(1): 145-147, 03/02/2015. graf
Article in English | LILACS | ID: lil-741613


Trichuris trichiura is a soil-transmitted helminth which is prevalent in warm, moist, tropical and subtropical regions of the world with poor sanitation. Heavy whipworm can result either in Trichuris dysenteric syndrome - especially in children - or in a chronic colitis. In heavy infections, worms can spread proximally and may cause ileitis. Here we provide first microscopic evidence for a T. trichiura adult worm embedded in the rectum of a post-Colonial Brazilian adult mummy. During Colonial and post-Colonial times, many European chroniclers described a parasitic disease named Maculo whose symptomatology coincides with heavy helminthiasis. Based on our findings and on comparison of ancient textual evidence with modern description of heavy whipworm, we feel confident in considering that the two syndromes are expressions of the same pathological condition.

Animals , Female , Male , Mice , Dietary Supplements , Diabetes Mellitus, Experimental/diet therapy , Hyperglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Liriope Plant/chemistry , Plant Tubers/chemistry , Polysaccharides/therapeutic use , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Dietary Supplements/adverse effects , Ethnopharmacology , Gene Expression Regulation, Enzymologic , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/isolation & purification , Insulin Resistance , Liver Glycogen/metabolism , Liver/enzymology , Liver/metabolism , Liver/pathology , Medicine, Chinese Traditional , Pancreas/metabolism , Pancreas/pathology , Plant Extracts/administration & dosage , Plant Extracts/adverse effects , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Polysaccharides/administration & dosage , Polysaccharides/adverse effects , Polysaccharides/isolation & purification , Random Allocation , Rats, Wistar , Toxicity Tests, Acute