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AIM: There is a need for effective treatments for non-alcoholic fatty liver disease (NAFLD) that are economically inexpensive, and have few side effects. The present study aimed to investigate exercise training and silymarin on hepatocyte death factors in rats with liver damage. METHODS: Forty-nine male Wistar rats were assigned to seven groups: sedentary control, fatty liver control (DEX), fatty liver + high-intensity interval training (HIIT), fatty liver + HIIT + silymarin (HIIT + SILY), fatty liver + continuous training (CT), fatty liver + CT + silymarin (CT + SILY), and fatty liver + silymarin (SILY). A subcutaneous injection of dexamethasone for 7 days was used to induce fatty liver in rats. Masson's trichrome and hematoxylin-eosin staining were done to evaluate hepatic injury. The hepatocyte apoptosis was determined by TUNEL assay. Real-Time PCR was conducted to evaluate the gene expressions of caspase-9, adenosine monophosphate-activated protein kinase (AMPKα1), mitofusin 2 (Mfn2), and damage-regulated autophagy modulator (DRAM). Liver tissue changes and serum levels of liver enzymes were also evaluated. RESULTS: Liver apoptosis was decreased in the CT, HIIT, HIIT + SILY and CT + SILY groups compared to the DEX group. Both continuous and high-intensity training models produced beneficial alterations in liver morphology and hepatic injuries that were significant in exercise training + silymarin group. This impact was accompanied by increased AMPKα1 and DRAM gene expression and decreased caspase-9 and Mfn2 gene expression. Liver enzyme levels were high in the DEX group and treatment with silymarin significantly reduced it. CONCLUSION: Silymarin supplementation combined with interval or continuous training substantially improves DEX-induced hepatic steatosis and hepatocyte injury mostly through suppressing liver apoptosis and upregulating autophagy, which may provide a novel perspective for NAFLD treatment.
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Apoptose , Autofagia , Dexametasona , Fígado , Hepatopatia Gordurosa não Alcoólica , Condicionamento Físico Animal , Ratos Wistar , Silimarina , Animais , Silimarina/farmacologia , Autofagia/efeitos dos fármacos , Dexametasona/farmacologia , Apoptose/efeitos dos fármacos , Masculino , Ratos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Modelos Animais de Doenças , Caspase 9/metabolismo , Caspase 9/genética , GTP Fosfo-Hidrolases/metabolismo , GTP Fosfo-Hidrolases/genética , Proteínas MitocondriaisRESUMO
Methotrexate (MTX), as a folic acid antagonist, is an effective drug in treating a wide range of malignancies and autoimmune diseases. However, the clinical use of MTX has been limited due to its side effects, the most common of which is hepatotoxicity. In this study, rats were randomly divided into six groups: three treatment groups received methotrexate and different doses of astaxanthin (AX) for 14 days. At the end of the study, blood samples were collected to determine serum levels of ALT, AST, ALP, and LDH. Also, liver tissues were isolated to evaluate antioxidant enzymes and markers of oxidative stress, histopathological damage, and expression of NF-E2-related transcription factor (Nrf2) and Heme oxygenase-1 (HO-1) genes. The results showed that administration of MTX significantly increased the levels of ALT, AST, ALP, and LDH in the blood, markers of oxidative stress, and histopathological damage in liver tissue and significantly reduced the levels of antioxidant enzymes and the expression of Nrf2 and HO-1 genes. On the other hand, treatment with AX decreased blood levels of ALT, AST, ALP, and LDH and oxidative stress markers and remarkably raises the activity of antioxidant enzymes and expression of Nrf2 and HO-1 genes in liver tissue. In addition, histopathological lesions were improved with AX administration. The findings of this study indicated that AX may be useful for the prevention of MTX-induced hepatotoxicity by improving oxidative and inflammatory changes.
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Doença Hepática Induzida por Substâncias e Drogas , Metotrexato , Ratos , Animais , Metotrexato/toxicidade , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Ratos Wistar , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fígado , Estresse Oxidativo , Doença Hepática Induzida por Substâncias e Drogas/metabolismoRESUMO
The aim of the current study was to determine protective effects of betaine on depressive-like behaviors in zinc oxide nanoparticles (ZnO NPs) exposed mice. Forty male mice randomly allocated into four experimental groups. Group 1 kept as control and groups 2-4 received oral administration of betaine (30 mg/kg), ZnO NPs (600 mg/kg), and ZnO NPs (600 mg/kg) 1 h after pre-administration of betaine (30 mg/kg) for 7 days, respectively. Then, forced swimming test (FST), tail suspension test (TST), open field test (OFT), and rotarod tests were done. Furthermore, serum malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) levels were determined. Hippocampal tissue samples were collected for histopathological assessment. According to the results, treatment with ZnO NPs significantly increased immobility time in the FST and TST (P<0.05). Betaine significantly decreased immobility time in the FST and TST (P<0.05). Pretreatment with betaine significantly decreased ZnO NPs-induced alterations in the FST and TST (P<0.05). The duration of staying on the rotarod and the numbers of crossings in the OFT significantly decreased in the mice that received ZnO NPs (P<0.05). These results were significantly improved in betaine+ZnO NPs treated mice as compared to the ZnO NPs group (P<0.05). Treatment with ZnO NPs significantly increased serum MDA level while decreased SOD and GPx compared to the control group (P<0.05). These changes were effectively ameliorated by pretreatment with betaine compared to the ZnO NPs group (P<0.05). No significant effect on serum TAC level was observed in all groups (PË0.05). Administration of ZnO NPs decreased the thickness of hippocampus and pyramidal neurons in the hippocampal dentate gyrus (DG) and CA1 regions were sparsely arranged. Pretreatment with betaine caused an improvement in the histological features of the hippocampus when compared with ZnO NPs-treated mice. Taken together, these results suggest that betaine has protective role against ZnO NPs-induced toxicity in mice.
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Nanopartículas , Óxido de Zinco , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Betaína/farmacologia , Glutationa Peroxidase , Masculino , Malondialdeído , Camundongos , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Óxido de Zinco/farmacologiaRESUMO
Aims:A controlled release drug delivery system loaded with buprenorphine and ketorolac was synthesized and used in the experimental model of bone defect and while evaluating the inflammatory response, the repair process in the defects was investigated.Materials and methods:To determine the effectiveness of the synthesized the mentioned systems, 5 groups were defined; the control group, the chitosan hydrogel receiving group (chitosan group), the ketorolac-loaded chitosan hydrogel group (ketorolac group), the buprenorphine-loaded chitosan hydrogel receiving group (buprenorphine group), and the chitosan hydrogel-loading group loaded with a combination of ketorolac and buprenorphine (ketorolac-buprenorphine group). Results:The results showed that the population of leukocytes (tWBC) and neutrophils on different days of the study in the control group compared to other groups had a significant increase (P < 0.05) while on day 7 of the study in the ketorolac group these parameters decreased significantly compared to other groups (P < 0.05). While examining the histological changes in the experimental defect created in the proximal tibia of rats at different times, some inflammatory indices such as total and differential leukocyte population, plasma concentrations of TNF-α and IL-6 were compared in different groups (P < 0.05). The various evaluated data showed that among the different groups, in the control and ketorolac-buprenorphine groups, there was the lowest and highest control of inflammatory response and bone repair, respectively.Conclusion:In the ketorolac group due to the impact of ketorolac on leukocyte populations the best bone healing can be expected among the different treatment groups.
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Buprenorfina , Quitosana , Animais , Preparações de Ação Retardada , Epífises , Hidrogéis , Cetorolaco , Ratos , TíbiaRESUMO
Mesenchymal stem cells (MSCs) own the capacity to secrete trophic factors as exosomes which play significant roles in regulating the functions of other cells and preventing inflammation. Due to the inflammatory process in chronic non-bacterial prostatitis (CNP) and the ambiguity in the treatment of this disease, the present study was aimed to investigate the therapeutic use of adipose-derived MSC exosomes in an animal model of CNP. MSCs were first isolated from rat subcutaneous adipose tissue, and exosomes were extracted from them. Specific features of exosomes were characterized by a scanning electron microscope, western blot technique, and Dynamic Light Scattering methods. To establish CNP in rats, intraprostatic injection of Freund's complete adjuvant was done. After confirmation of prostatitis, intraprostatic injections of exosomes were performed for treatment. Histological evaluation revealed that treatment with exosomes resulted in a relative improvement of lesions caused by CNP. The expression of p-NF-κB and p-IκBα proteins along with inflammatory markers was significantly increased in the CNP group, which treatment with exosomes significantly reduced their expression as well as IL-1ß and TNF-α proteins. The antioxidant effects of exosomes were also determined by significantly regulating glutathione peroxidase and superoxide dismutase activity and malondialdehyde levels in these animals. Our results cautiously suggest the therapeutic effects of MSC-derived exosomes against CNP-induced prostatitis through their antioxidant and anti-inflammatory activities, which should be further considered in the future.
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Tecido Adiposo/metabolismo , Exossomos , Células-Tronco Mesenquimais/metabolismo , Prostatite , Animais , Doença Crônica , Exossomos/metabolismo , Exossomos/transplante , Masculino , Prostatite/metabolismo , Prostatite/terapia , RatosRESUMO
Cells translate the mechanosensing of extracellular matrix component dysregulation and stiffness into the signal transduction including Osteopontin (OPN) through the Hippo pathway. But how extracellular matrix (ECM) component dysregulation and stiffness are ultimately linked to transitional cell carcinoma (TCC) development remains poorly understood. This study was aimed to evaluate the possible links between ECM component alteration after cancer surgery and OPN and Yes-associated protein (YAP) expression in TCC and adjacent tissues. In this study, we used 50 TCC (25 newly diagnosed and 25 recurrent) and 50 adjacent tissues to determine the tissue stiffness using atomic force microscopy. The mRNA expression of SPP1, Indian hedgehog (IHH), and YAP was also determined using qRT-PCR. Western blotting and ELISA were performed to assess the tissue and serum levels of OPN, respectively. To assess the glycoproteins and elastic fibers content, Periodic Acid Schiff, and Verhoeff-Van Gieson Staining were performed, respectively. Matrix stiffness was markedly higher in TCCs than adjacent tissues (p < 0.05). Gene expression analysis showed that YAP, SPP1, and IHH genes were upregulated in TCC tissues (p < 0.05). Additionally, the OPN protein overexpression was observed in the tissue and the serum of TCC patients (p < 0.05). We also found that glycoproteins, elastic fibers content of recurrent TCC tissues was remarkably higher as compared to adjacent tissues (p < 0.05). Our results suggest that glycoproteins and elastic fibers content modulation and ECM stiffness may upregulates the expression of YAP, SPP1 and IHH genes, and possibly contribute to the TCC development and relapse.
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Carcinoma de Células de Transição/genética , Matriz Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Recidiva Local de Neoplasia/genética , Osteopontina/genética , Neoplasias da Bexiga Urinária/genética , Proteínas de Sinalização YAP/genética , Idoso , Carcinoma de Células de Transição/sangue , Estudos de Casos e Controles , Elastina/metabolismo , Feminino , Expressão Gênica , Proteínas Hedgehog/genética , Via de Sinalização Hippo/genética , Humanos , Masculino , Recidiva Local de Neoplasia/sangue , Osteopontina/sangue , Proteoglicanas/metabolismo , Regulação para Cima/genética , Neoplasias da Bexiga Urinária/sangueRESUMO
OBJECTIVE: Bladder cancer is the 9th leading cause of human urologic malignancy and the 13th cause of death worldwide. Increased collagen cross-linking, NIDOGEN1 expression and consequently stiffness of extracellular matrix (ECM) may be responsible for the mechanotransduction and regulation of transcriptional co-activator with PDZ-binding motif (TAZ) and transforming growth factor ß1 (TGF-ß1) signaling pathways, resulting in progression of tumorigenesis. The present study aimed to assess whether type 1 collagen expression is associated with TAZ nuclear localization. MATERIALS AND METHODS: In this case-control study, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analysis were performed to evaluate the activation of the TAZ pathway in patients with bladder cancer (n=40) and healthy individuals (n=20). The ELISA method was also conducted to measure the serum concentrations of TGF-ß1. Masson's trichrome staining was carried out to histologically evaluate the density of type 1 collagen. RESULTS: Our findings that the expression levels of COL1A1, COL1A2, NIDOGEN1, TAZ, and TGF-ß1 genes were overexpressed in patients with bladder cancer, and their expression levels were positively associated with the grade of bladder cancer. The immunohistochemical analysis demonstrated that the nuclear localization of TAZ was markedly correlated with high-grade bladder cancer. We also found that TAZ nuclear localization was substantially higher in cancerous tissues as compared with normal bladder tissues. Masson's trichrome staining showed that the tissue density of type I collagen was considerably increased in patients with bladder cancer as compared with healthy subjects. CONCLUSION: According to our findings, it seems the alterations in the expression of type I collagen and NIDOGEN1, as well as TAZ nuclear localization influence the progression of bladder cancer. The significance of TGF-ß1 and TAZ expression in tumorigenesis and progression to high-grade bladder cancer was also highlighted. However, a possible relationship between TGF-ß1 expression and the Hippo pathway needs further investigations.
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The purpose of this study was to evaluate the neuroprotective effect of local implantation of a controlled delivery system of chitosan hydrogel loaded with selenium nanoparticles in rats with spinal cord injury (SCI). For this purpose, 60 adult female rats were randomly divided into three equal groups. In all three groups, SCI was induced by aneurysm clamping at the level of thoracic vertebrae under inhaled anesthesia with isoflurane. In one group after spinal cord injury, chitosan hydrogels loaded with selenium nanoparticles (treatment group), and in the other group, only chitosan hydrogels (positive control group) were placed at the site of injury. In the last group (negative control), no material was placed in the injury site. Hematoxylin-eosin and glial fibrillary acidic protein (GFAP) staining evaluated histological changes at the site of injury on days 3, 7, 21, and 28 after surgery. Evaluations show that hemorrhage and inflammation also have a marked decrease in inflammatory cells at different times in the treatment group. This decrease was also seen in the chitosan group but was less severe than in the treatment group. The formation of nerve fibers was also observed in the treatment group over time of injury. Immunohistochemical studies of damaged tissue showed higher expression of GFAP protein in the astrocytes of the treatment group than in the other two groups and the chitosan group compared with the negative control group. A controlled drug delivery system containing selenium nanoparticles seems to play a role in the protection of nerve cells through its anti-inflammatory effect.
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Quitosana , Nanopartículas , Selênio , Traumatismos da Medula Espinal , Animais , Quitosana/uso terapêutico , Sistemas de Liberação de Medicamentos , Feminino , Hidrogéis/uso terapêutico , Ratos , Ratos Sprague-Dawley , Selênio/uso terapêutico , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológicoRESUMO
Changes in the cellular microenvironment play a critical role in the development of bladder cancer (BC). Yes-associated protein (YAP), a central mediator of the Hippo pathway, functions as a nuclear sensor of mechanotransduction that can be induced by stiffness of the extracellular matrix (ECM), including stiffness resulting from surgical manipulations. We aimed to clarify the possible association between surgically-related ECM stiffness and YAP activation in BC patients. We compared 30 bladder cancer tissues with grade II (n = 15 recurrent and n = 15 newly diagnosed) with 30 adjacent healthy tissues. Atomic force microscopy showed that patients with recurrent BC had stiffer ECM than newly diagnosed patients (P < 0.05). Gene expression profiles showed that ß1 integrin (ITGB1), focal adhesion kinase (FAK), CDC42, and YAP were upregulated in cancerous tissues (P < 0.05); additionally, ß1 integrin activation was confirmed using a specific antibody. Nuclear localization of YAP was higher in recurrent cancerous tissues compared with newly diagnosed and it was positively associated with higher stiffness (P < 0.05). Our results suggest that postsurgery-induced ECM stiffness can influence integrin-FAK-YAP activity and thereby YAP trafficking to the nucleus where it contributes to BC progression and relapse.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Mecanotransdução Celular/fisiologia , Fatores de Transcrição/metabolismo , Microambiente Tumoral/fisiologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/cirurgia , Proteínas Adaptadoras de Transdução de Sinal/química , Idoso , Biomarcadores Tumorais/química , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Fatores de Transcrição/química , Neoplasias da Bexiga Urinária/patologia , Proteínas de Sinalização YAPRESUMO
Tyrosine kinase inhibitors (TKIs) have been developed as therapeutic compounds for inhibiting the progression of liver fibrosis. In the present study, the simultaneous treatment of Nilotinib (TKIs) and Losartan was studied. Forty rats were divided into eight groups of fibrosis induced by carbon tetrachloride (CCl4) and therapeutics (Nilotinib, Losartan, and combination therapy). In the end, serum parameters of the liver and gene expression analysis of transforming growth factor-ß1, its receptors (TßRII), platelet-derived growth factor, its receptors (PDGFRß), matrix metalloproteinases (MMP-2 and MMP-9), tumor necrosis factor-α, cytochrome P450 2E1, and collagen1 type 1 were performed. The oxidant/antioxidant factors were also analyzed. Histopathology analysis along with α-SMA immunohistochemistry and hydroxyproline evaluation was also conducted for a more in-depth study. The overall results indicated a better therapeutic effect of co-treatment of Nilotinib-Losartan in comparison with the treatment of each of them alone. Interestingly, some gene and protein factors and fibrotic indices were reduced even to the normal levels of the control group. The results of this study suggest that co-administration of these two combinations, strengthens their anti-fibrotic properties and, due to the routine use of these compounds against AML and blood pressure, these compounds can be used with caution against human liver fibrosis.
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Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Tetracloreto de Carbono/toxicidade , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/prevenção & controle , Losartan/uso terapêutico , Proteínas Tirosina Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Quimioterapia Combinada , Losartan/administração & dosagem , Losartan/farmacologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Proteínas Tirosina Quinases/administração & dosagem , Proteínas Tirosina Quinases/farmacologia , Pirimidinas/administração & dosagem , Pirimidinas/farmacologia , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta1/análise , Aumento de Peso/efeitos dos fármacosRESUMO
This study was conducted with the objective of identifying the types of gross and histopathological lesions in lungs of sheep slaughtered between March 2013 to February 2014 at Kermanshah abattoir, west of Iran. A total of 1200 slaughtered sheep lungs was inspected during the study period. Pulmonary lesions were detected in 445 (37.08%) carcasses, grossly. Lesions were further subjected for detail histopathological examinations. On microscopic examination, most lungs had more than one type of lesions and thirteen different lesions were observed. The most common lesions were bronchopneumonia (13.33%), pulmonary emphysema (4.25%), hydatid cyst (4.16%), interstitial pneumonia (3.58%), abscess (3.33%), atelectasis (2.83), Pleurisy (1.66), bronchiectasis (1.41), verminous pneumonia (0.91%) and pulmonary adenomatosis (0.25%). The highest prevalence of pulmonary lesions was observed in the winter, which differences were significant in compared to other seasons (P=0.007). This study demonstrates that lung diseases and lesions represent a serious problem and may continue to be a drawback to livestock industry and may pose health risks to meat consumers from contrasting zoonotic diseases in western Iran. So designing of serious prevention and treatment programs are very important in our region.
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Pneumopatias/patologia , Pulmão/patologia , Doenças dos Ovinos/patologia , Animais , Irã (Geográfico) , OvinosRESUMO
Feline lower urinary tract diseases are known to be life threatening conditions in cats, especially when they occur as obstructive diseases in males. Early diagnosis and treatment is necessary, otherwise it may lead to death. A 3-year-old male Persian cat was referred to the clinic with a history of anuria, lethargy, loss of appetite and exploratory cystotomy 6 months ago due to urethral obstruction following urolithiasis. Urinary bladder was enlarged and painful on palpation and urine accumulation was observed in ultrasonography. Biochemical and hematological analyses revealed hypocalcemia, hyperphosphatemia and hyperkalemia and increase in blood urea nitrogen, creatinine, white blood cell (WBC), red blood cell (RBC) and hematocrit. Urine analysis showed a turbid appearance, protein 1+, blood 3+, pH reduction, increased WBCs and RBCs and presence of bacteria, calcium oxalate crystals and epithelial cells. Urine culture reveled Staphylococcus saprophyticus. Postoperatively, microscopic examinations of the urinary bladder biopsy showed pathological lesions of bacterial cystitis. Based on these findings, bacterial cystitis and urethral obstruction due to post-operative urinary tract infections were diagnosed. For treatment, electrolyte imbalances were corrected firstly, cystotomy was performed and a catheter was conducted into the urethra; then, urethra was flushed and obstruction was resolved. Ampicillin was effective in reducing the bacterial count in urine. Despite the fact that cystotomy is a common procedure in veterinary medicine, clinicians should be aware of its complications such as post-operative urinary tract infections.
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Osteoma is an uncommon bone tumor in avian species and other animals. A 2-year-old male canary (Serinus canaria) with a history of an oval mass in the left wing for several months was examined. Radiographs showed a radio-opaque mass. Upon the bird's owner request, the canary was euthanatized and submitted for necropsy. The histopathologic examination revealed numerous trabeculae consisting of both woven and lamellar bone covered by one to several rows of normal osteoblasts. The trabeculae were closely packed, having only small intertrabecular spaces which contained proliferating osteoblasts, sinusoids and myeloid tissue. Based on clinical, radiographic, and histopathologic findings, the mass was diagnosed as extraskeletal osteoma. To the best of authors' knowledge, extraskeletal osteoma has not been reported in in avian species so far, and this is the first report of osteoma tumor in the birds. However, benign tumors of bones are extremely rare in the birds, osteoma should be considered as a differential diagnosis in the birds with bone lesions.
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CONTEXT: The active ingredients of traditional medical herbs have been the focus of scientific interests. OBJECTIVE: This study was designed to explore the mechanisms of actions of parthenolide on nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: Thirty-five male Wistar rats were fed high-fat diet (HFD) for eight weeks with or without an intraperitoneal injection of parthenolide to develop NAFLD. Liver triacylglycerol (TG), total antioxidant capacity (TAC), total oxidative status (TOS), thiobarbituric acid reactant substances (TBARs), total thiol groups and tumor necrosis factor alpha (TNF-α) and cytochrome P4502E1 (CYP2E1) levels as well as liver ALT, AST and catalase activities were determined. In addition, quantitative real-time PCR was performed to obtain hepatic gene expression levels of TNF-α, CYP2E1 and nuclear factor-κB (NF-κB). RESULTS: HFD caused a significant weight gain and increased liver TG content as well as alteration in ALT and AST activities, which were attenuated after administration of parthenoide (p < .05). Weakened liver antioxidant system (TAC, total thiol groups and catalase activity) and increased oxidative stress markers (TBARs and TOS) were mainly ameliorated by parthenolide treatment (p < .05). Increased hepatic TNF-α, NF-κB and CYP2E1 at the both gene expression and protein levels were found associated with necroinflammatory changes in histopathological observations and were abrogated almost completely after parthenolide treatment. Oxidative and inflammatory changes observed in HFD fed rats were indicative of NAFLD, which were suppressed with parthenolide treatment. CONCLUSIONS: Based on these results, parthenolide might be a candidate agent for preventing NAFLD due to its anti-inflammatory and anti-oxidative potency.
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Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Substâncias Protetoras/farmacologia , Sesquiterpenos/farmacologia , Alanina Transaminase/metabolismo , Animais , Antioxidantes/farmacologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Fígado/metabolismo , Masculino , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Triglicerídeos/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVES: Dasatinib, a potent and broad-spectrum tyrosine kinase inhibitor, is approved for the treatment of imatinib-resistant chronic myelogenous leukemia. The aim of this study was to evaluate the anti-fibrotic, anti-inflammatory and antioxidant effects of this agent against CCl4-induced hepatic fibrosis and oxidative status. MATERIALS AND METHODS: Experimental fibrosis was induced in Wistar male rats by 12 weeks of CCl4 administration (i.p.). During the last 8 weeks of injection, rats were gavaged daily with Dasatinib (10 mg/kg). To evaluate anti-inflammatory and anti-fibrotic effects of Dasatinib, histopathological examination of liver tissue was performed and serum ALT and AST activities, oxidant, antioxidant parameters and hepatic tumor necrosis factor alpha (TNF-α) were examined. Moreover, transforming growth factor (TGF-ß1), platelet derived growth factor (PDGF) and TNF-α mRNA expressions were also evaluated by real time polymerase chain reaction. RESULTS: Dasatinib administration induced a significant reduction of ALT and AST activities (p < .001) and Malondialdehyde (MDA) content in CCl4 injected rats (p < .05). Concomitantly hepatic protein and mRNA expression of TNF-α, mRNA expression of TGF-ß1 and PDGF were increased due to CCl4 intoxication (p < .001), but Dasatinib treatment could significantly ameliorate these mediators at the level of gene expression (p < .01) and protein level of TNF-α (p < .001). The necro-inflammatory changes in histopathological finding, nitric oxide and hydroxyproline level were also increased during 12 weeks of CCl4 administration which was significantly attenuated by Dasatinib (p < .01). DISCUSSION AND CONCLUSION: Our findings indicate that Dasatinib can be cautiously an anti-fibrotic, anti-inflammatory and anti-oxidative agent in clinical setting.
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Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Intoxicação por Tetracloreto de Carbono/tratamento farmacológico , Dasatinibe/farmacologia , Cirrose Hepática/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Intoxicação por Tetracloreto de Carbono/imunologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/imunologia , Masculino , Estresse Oxidativo/imunologia , Ratos , Ratos WistarRESUMO
Hydatidosis is one of the important zoonotic diseases that cause considerable economic losses and public health problems worldwide. This study was conducted to determine the prevalence Echinococcus granulosus in people and slaughtered animals in Kermanshah province, west of Iran. Hospitals data and meat-inspection records in Kermanshah abattoir were used in this study. A total number of 32,130 slaughtered livestock (7000 cattle, 19,950 sheep and 5180 goats) was inspected in the 3-year period and overall 2043 (6.35 %) were infected. The highest and lowest prevalence was recorded in cattle and goats, respectively. In human, Cystic echinococcosis affected more females (54 %) than males (46 %) with a 1.17 male to female ratio. Rate of disease in urban and rural regions were 46 and 54 %, respectively. The youngest and the oldest patient operated were 7 and 87 years old, respectively, and the age group 21-40 years (41.2 %) were the most affected. A significantly higher number of hydatid cysts were recorded in the liver than in other sites. The ratio of hepatic hydatidosis to pulmonary hydatidosis was 2.46. The results showed that hydatidosis is of great importance in this area and serious attention is needed to prevent and control the disease.
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Cysticercusovis, the intermediate stage of a canine tapeworm, Taenia ovis, produces cystic lesions in the skeletal and cardiac muscle of sheep which, if numerous, will result in the condemnation of an entire carcass. This study was carried out between March 2013 and March 2014 to estimate the prevalence of Taenia oviscysticercosis in sheep slaughtered at the Kermanshah municipal abattoir, in western Iran. Of 69,198 sheep examined, 833 (1.27 %) were infected with cysticerci of Taenia ovis. The prevalence of C. ovis was significantly higher in males than females (P < 0.05). Seasonal analysis revealed significantly higher prevalence in spring (1.8 %) than other seasons (P < 0.005). The heart muscles (29.7 %), diaphragm (18.8 %), masseter muscles (18.2 %) and tongue (15.5 %) were the main predilection sites of the cysts. The cysts of ovinecysticercosis were also identified on the triceps, intercostal muscles, thigh muscles, intestinal mucosa, liver and Spleen. This parasite caused extensive damage resulting in infiltrative, degenerative changes, necrosis and exudation mainly in the vicinity of cysts. The results indicate that the prevalence of C. ovis in this area is high. Therefore improving the standard of disease prevention and control on farms is necessary.
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A retrospective study was carried out from 2008 to 2013 to estimate the prevalence of hydatidosis in ruminants slaughtered at the Kermanshah municipal abattoir, in western Iran. A total number of 663,633 livestock (393,585 sheep, 81,080 goats and 188,968 cattle) slaughtered in the 5-year period and overall 9,524 (1.43 %) livers and 13,147 (1.98 %) lungs were condemned. The lungs were more frequently infected with hydatid cysts than the livers in all animal species. The average prevalence of hydatidosis was 2.7 % in this area. The prevalence of Echinococcus granulosus infection recorded in the present study was generally lower than those reported from other regions of Iran. Greater awareness among farmers, destruction of organs containing hydatid cysts, prevention of access of dogs to raw offals and implementation of national rabies control program could be responsible factors. The results showed a significant difference (p < 0.001) in the prevalence of hydatidosis among studied animals with higher prevalence in cattle than sheep, with the lowest prevalence recorded in goats. However the annual prevalence of liver and lung condemnations due to hydatidosis was decreased in some years, but the overall trend had a variable pattern in the prevalence of hydatidosis over the study period. Data showed a significant seasonal pattern for hydatidosis in all studied animals. Liver and lung condemnations due to hydatidosis were higher in the fall for sheep and cattle, whereas in goats were higher in summer. This could be attributed to various factors such as sources of slaughtered animals, changes in management practice and ecological factors. The current results suggest that a systematic investigation that lead to a disease control strategy is required to reduce the economic and public health consequences of hydatidosis. In addition, the present survey provides baseline data for the future monitoring of this potentially important parasitic disease in the region.
RESUMO
In the present study, we described cyto-histopathological features and immunophenotyping of the large B-cell lymphoma in an 8-year-old mixed breed dog with applying the World Health Organization (WHO) system of classification of canine lymphomas. In fine-needle aspiration (FNA), lymph nodes were involved by neoplastic cells of intermediate to large size with deep blue cytoplasm; consist of centroblasts, immunoblast and medium-sized cells. Histopathologically, the follicles and sinuses of lymph nodes were replaced by sheets of numerous immunoblasts (less than 90.0% of total cells) and centroblasts. Numerous mitotic figures were also observed. Immunohistochemical analysis presented that the neoplastic cells express B-cell phenotype CD20 and CD79a, but do not stain for T phenotype CD3. On the basis of cytology, histopathology and immunohistochemical findings, the present tumor was diagnosed as diffuse large B-cell lymphoma, high-grade centroblastic type (DLBCL-CB) according to WHO histological classification. Applying this classification system for diagnosis of canine lymphomas is very useful and has a high accuracy and consistency. However, further co-operative studies between clinicians and pathologists should be performed, in order to improve the effectiveness of this classification.
RESUMO
Heterotopic ossification is the process of pathologic bone formation in soft tissue structures that usually do not form bone. An immature golden eagle ( Aquila chrysaetos ) was examined 2 months after a gunshot wound in the right wing. A solid oval mass with a gun pellet at its core was found attached to the ulna by a bony pedicle and was surgically excised. Heterotopic ossification secondary to gunshot and fragment wounds in the right ulna was diagnosed based on clinical, radiographic, and histopathologic findings. This report is the first to describe heterotopic ossification occurring around a gun pellet in a bird.