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Int. j. morphol ; 38(3): 804-810, June 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1098323


Honey is a natural antioxidant that its protective effects have been proven against ischemia-reperfusion (IR) injury. The aim of this study was to evaluate the ameliorative effect of Persian Honey, Apis mellifera meda skorikov, on gastrocnemius muscle IR injury. Eighty adult male Sprague-Dawley rats weighing 250-300 g were used. They were divided into ten groups (N=8 per group). The ischemia was conducted with a silk suture 6-0 using the slipknot technique. All groups were rendered in ischemic for 3 h, and reperfused for various times of 3 days (3-day reperfusion), 7 days (7-day reperfusion), 14 days (14-day reperfusion), and 28 days (28-day reperfusion). Half of the groups had experimental honey (5 %) treatment immediately after ischemia. After reperfusion, the rats, based on the grouping, were killed with high doses of anesthetic, and the gastrocnemius muscles were removed and fixed. After the tissue processing, the evaluation of edema and mast cells infiltration was performed with hematoxylin-eosin and toluidine blue staining, respectively. TNF-α was detected with immunohistochemistry method. The amount of TNF-α as an index of acute inflammatory except the 3rd day significantly decreased on the other day of reperfusion (7th, 147th and 287th days). The mast cells infiltration was significantly decreased on 77th and 147th days. The tissue edema was decreased significantly in honey administrated group in the comparison with placebo groups. Honey administration can reduce damage caused by ischemia-reperfusion in the rat gastrocnemius muscle.

La miel es un antioxidante natural; sus efectos protectores han sido probados contra la lesión por isquemiareperfusión (IR). El objetivo de este estudio fue evaluar el efecto de mejora de la miel persa Apis mellifera meda skorikov, en la lesión por IR del músculo gastrocnemio. Se utilizaron 80 ratas Sprague-Dawley macho adultas con un peso entre 250 y 300 g divididas en diez grupos (N = 8 por grupo). La isquemia se realizó con una sutura de seda 6-0 utilizando la técnica slipknot permaneciendo isquémicos durante 3 h. La reperfusión se realizó durante varios tiempos de 3 días, 7 días (reperfusión de 7 días), 14 días (reperfusión de 14 días) y 28 días (28 días reperfusión). La mitad de los grupos recibió tratamiento experimental con miel (5 %) inmediatamente después de la isquemia. Después de la reperfusión, las ratas, fueron sacrificadas con altas dosis de anestésico, y los músculos gastrocnemios fueron removidos y fijados. Después de procesar el tejido, se realizó la evaluación del edema y la infiltración de mastocitos se realizó con tinción de hematoxilina-eosina y azul de toluidina, respectivamente. TNF-α se detectó con el método de inmunohistoquímica. La cantidad de TNF-α como índice de inflamación inflamatoria aguda, excepto en el tercer día, disminuyó significativamente al día siguiente de la reperfusión (7, 14 y 28 días). La infiltración de mastocitos disminuyó significativamente a los 7 y 14 días. El edema tisular disminuyó significativamente en el grupo administrado con miel en comparación con los grupos placebo. El tratamiento con miel puede reducir el daño causado por la isquemia-reperfusión en el músculo gastrocnemio de la rata.

Animais , Masculino , Ratos , Traumatismo por Reperfusão/complicações , Apis mellifica/administração & dosagem , Músculo Esquelético/lesões , Mel , Imuno-Histoquímica , Traumatismo por Reperfusão/tratamento farmacológico , Apis mellifica/farmacologia , Ratos Sprague-Dawley , Músculo Esquelético/efeitos dos fármacos , Substâncias Protetoras
J. bras. nefrol ; 41(3): 315-322, July-Sept. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1040245


Abstract Introduction: It is hypothesized that increased macrophage migration inhibitory factor (MIF) expression may contribute to diabetic nephropathy (DN) pathogenesis. The aim of the present study was to investigate the renal effects of MIF inhibition in a diabetic experimental model. Methods: Eighteen male Wistar rats (230 ± 20 g) were divided into three groups: 1) control, 2) diabetic (STZ, 50 mg/kg, dissolved in saline, ip), 3) diabetic + MIF antagonist (p425, 1 mg/kg per day, ip, on the 21th day, for 21 consecutive days). The treatment started since we founwd a significant increase in urine albumin excretion (UAE) rate in the diabetic rats in comparison with the control rats. The rats were kept individually in metabolic cages (8 AM-2 PM) and urine samples were collected in the 21 and 42th day. At the end, blood and tissue samples were collected for biochemical (BS, UPE, urine GAG, BUN, Cr, Na, and K) and histological analyses. Results: The results of this study showed that MIF antagonist (p425) significantly decreased urine protein and GAG excretion, urine protein/creatinine ratio, and serum BUN and Cr in the streptozotocin-induced DN in the rats. Pathological changes were significantly alleviated in the MIF antagonist (p425)-administered DN rats. Conclusion: Collectively, these data suggested that MIF antagonist (p425) was able to protect against functional and histopathological injury in the DN.

Resumo Introdução: Supõe-se que elevações da expressão do fator de inibição da migração de macrófagos (MIF) possam contribuir para a patogênese da nefropatia diabética (ND). O objetivo do presente estudo foi investigar os efeitos renais da inibição do MIF em um modelo experimental diabético. Métodos: Dezoito ratos Wistar machos (230 ± 20g) foram divididos em três grupos: 1) controle, 2) diabético (STZ 50 mg/kg dissolvida em soro fisiológico, IP), 3) diabético + antagonista do MIF (p425 1 mg/kg por dia IP no 21o dia por 21 dias consecutivos). O tratamento começou após a identificação de aumento significativo na albuminúria nos ratos diabéticos em relação aos controles. Os ratos foram mantidos individualmente em gaiolas metabólicas (8h-14h) e amostras de urina foram colhidas no 21o e no 42o dia. Ao final do estudo, amostras de sangue e tecido foram colhidas para análises bioquímicas (BS, excreção urinária de proteína, excreção urinária de GAGs, BUN, Cr, Na e K) e histológicas. Resultados: O presente estudo demonstrou que o antagonista do MIF (p425) diminuiu significativamente proteinúria, excreção urinária de GAGs , relação proteína/creatinina na urina, BUN e Cr no grupo com ND induzida por estreptozotocina. As alterações patológicas foram significativamente abrandadas nos ratos com ND que receberam antagonista do MIF (p425). Conclusão: Coletivamente, os dados sugerem que o antagonista do MIF (p425) teve efeito protetor contra lesões funcionais e histopatológicas da ND.

Animais , Masculino , Ratos , Fatores Inibidores da Migração de Macrófagos/antagonistas & inibidores , Oxirredutases Intramoleculares/antagonistas & inibidores , Substâncias Protetoras/uso terapêutico , Substâncias Protetoras/farmacologia , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/terapia , Glicemia , Ratos Wistar , Estreptozocina/farmacologia , Creatinina/urina , Creatinina/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/urina , Diabetes Mellitus Experimental/sangue , Nefropatias Diabéticas/urina , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/sangue , Albuminúria/tratamento farmacológico , Modelos Animais de Doenças , Glicosaminoglicanos/urina , Rim/patologia , Ativação de Macrófagos
An. bras. dermatol ; 94(2): 198-203, Mar.-Apr. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1001146


Abstract BACKGROUND: Psoriasis is a systemic inflammatory disorder that involves complex pathogenic interactions between the innate and adaptive immune systems. The most accepted mechanism in the etiopathogenesis of psoriasis is the induction of inflammation with keratinocyte hyperproliferation. Granulysin (GNLY) is a cytolytic antimicrobial peptide (AMP) that is secreted together with granzyme and perforin from the granules of human cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. It has been immunohistochemically proven that the expression of granulysin is increased in lesions of psoriasis. OBJECTIVE: This study aimed to investigate the relationship between psoriasis disease and granulysin gene polymorphisms. METHODS: GNLY rs7908 and rs10180391 polymorphisms were studied by PCR-RFLP in 100 psoriasis patients under treatment in the Dermatology Polyclinic of Bulent Ecevit University. In addition, 100 healthy individuals with similar age and sex distribution were used as a control group. RESULTS: In the control group, GNLY rs7908 CC genotype was significantly higher than in psoriasis patients (P= 0.031; OR= 0.305; Cl= 0.305 (0.121 - 0.773). In our study, the genotype distributions in patients and control groups were GNLY rs7908 (SNP) GG (51%, 37%), GC (41%, 44%), CC (8%, 19%); GNLY rs10180391 (SNP) from the CC (41%, 44%), CT (42%, % 41), TT (17%, 15%). STUDY LIMITATIONS: The study only included Turkish patients. CONCLUSION: Our findings showed that GNLY rs7908 CC genotype and C allele had a protective effect against psoriasis and decreased the disease severity (according to PASI score), whereas rs10180391 SNP did not show any effective role in psoriasis pathogenesis.

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Psoríase/genética , Antígenos de Diferenciação de Linfócitos T/genética , Psoríase/etiologia , Índice de Gravidade de Doença , Estudos de Casos e Controles , Expressão Gênica , Substâncias Protetoras , Alelos , Genótipo
Acta cir. bras ; 34(2): e201900209, 2019. graf
Artigo em Inglês | LILACS | ID: biblio-989056


Abstract Purpose: To explore the effect of milk fat globule-epidermal growth factor 8 (MFG-E8) on sepsis-induced acute kidney injury (SAKI). Methods: Male C57BL/6 mice were randomized to control, sham, CLP, CLP+PBS, and CLP+rmMFG-E8 groups. SAKI was induced by cecal ligation and puncture (CLP). Recombinant mouse MFG-E8 (rmMFG-E8) (20 μg/kg) or PBS (vehicle) was administered intraperitoneally. Blood, urine and renal tissue were collected at 24 h after CLP. Blood samples were tested for serum kidney injury biomarker and cytokines. Urine samples were collected to detect KIM-1, and NGAL. Real-time PCR was tested for Bax and Bcl-2. TUNEL staining was used to determine renal apoptosis. Western blot was used to detect the expression of Bax, Bcl-2, and proteins in the NF-κB pathway. Results: MFG-E8 alleviated SAKI by decreasing serum Cre, BUN, urine KIM-1 and NGAL and by mitigating renal pathological changes significant (p < 0.05). IL-1β, IL-6, TNF-α were significantly inhibited by MFG-E8 (p < 0.05). Apoptosis induced by SAKI was markedly suppressed by MFG-E8. Finally, MFG-E8 attenuated the activation of the NF-��B signaling pathway in SAKI. Conclusion: MFG-E8 has beneficial effects on SAKI, which may be achieved by inhibiting the NF-κB pathway.

Animais , Masculino , Ratos , NF-kappa B/antagonistas & inibidores , Sepse/complicações , Substâncias Protetoras/uso terapêutico , Lesão Renal Aguda/prevenção & controle , Proteínas do Leite/uso terapêutico , Antígenos de Superfície/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Lesão Renal Aguda/etiologia , Camundongos Endogâmicos C57BL
Acta cir. bras ; 34(9): e201900901, 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1054695


Abstract Purpose: To evaluate the effects of tadalafil (TD) in preventing histological alterations of the corpus cavernosum caused by isolated lesions of cavernous nerve (ILCN) and artery (ILCA) in rats. Methods: Fifty male Wistar rats were randomly assigned in five groups: G1: control; G2: bilateral ILCN; G3: bilateral ILCA; G4: ILCN+TD; G5: ILCA+TD. The cavernous bodies were submitted to histomorphometry, immunohistochemistry and biochemical analysis. Results: Nerve density was significantly higher in G2 and G4 compared to control (22.62±2.84 and 19.53±3.47 vs. 15.72±1.82; respectively, p<0.05). Smooth muscle density was significantly lower in G2 and G3 in comparison to G1 (12.87±1.90 and 18.93±1.51 vs. 21.78±1.81, respectively; p<0.05). A significant decrease in the sinusoidal lumen area was observed in G2 compared to controls (5.01±1.62 vs. 9.88±3.66, respectively; p<0.05) and the blood vessel density was increased in G2 and G3 (29.32±4.13 e 20.80±2.47 vs. 10.13±2.71, p<0.05). Collagen density was higher in G3 compared to G1 (93.76±15.81 vs. 64.59±19.25; p<0.05). Conclusions: Histomorphometric alterations caused by ILCN were more intense than those produced by vascular injury, but the collagen analyses showed more fibrosis in animals with ILCA. TD was effective in preventing the majority of the alterations induced by the periprostatic bundle injury.

Animais , Masculino , Pênis/inervação , Pênis/irrigação sanguínea , Substâncias Protetoras/farmacologia , Inibidores da Fosfodiesterase 5/farmacologia , Traumatismos dos Nervos Periféricos/prevenção & controle , Tadalafila/farmacologia , Pênis/efeitos dos fármacos , Pênis/patologia , Prostatectomia/efeitos adversos , Imuno-Histoquímica , Distribuição Aleatória , Reprodutibilidade dos Testes , Colágeno/análise , Colágeno/efeitos dos fármacos , Ratos Wistar , Tecido Elástico/anatomia & histologia , Tecido Elástico/efeitos dos fármacos , Disfunção Erétil/prevenção & controle
Acta cir. bras ; 33(12): 1061-1066, Dec. 2018. tab
Artigo em Inglês | LILACS | ID: biblio-973491


Abstract Purpose: To investigate the role of atenolol in the gene expression of caspase 1 (Casp1) and Bcl2L1 on vascular endothelium of rat intestine after ischemia and reperfusion (IR). Methods: Eighteen adult male Wistar rats were randomly divided into 3 groups (n=6): SG (Sham group): no clamping of the superior mesenteric artery; IRG: IR plus saline group: IRG+At: IR plus Atenolol group. Rats from IRG and IRG+At were subjected to 60 min of intestinal ischemia and 120 min of reperfusion. Atenolol (2mg/kg) or saline were injected in the femoral vein 5 min before ischemia, 5 min and 55 min after reperfusion. Thereafter, intestinal segments were appropriately removed and processed for Endothelial Cell Biology Rat RT2 Profiler PCR Array. Results: the anti-apoptotic Bcl2L1 gene expression was significantly down-regulated (-1.10) in the IRG and significantly up-regulated in the IRG+At (+14.15). Meanwhile, despite Casp1 gene expression was upregulated in both groups, it was significantly higher in the IRG (+35.06) than the IRG+At (+6.68). Conclusions: Atenolol presents antiapoptotic effects on rat intestine subjected to IR partly by the up-regulation of the anti-apoptotic Bcl2L1 gene expression. Moreover, atenolol can mitigate the pro-apoptotic and pro-inflammatory effects of Casp1 gene on rat intestine after IR.

Animais , Masculino , Atenolol/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Expressão Gênica/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Caspase 1/efeitos dos fármacos , Proteína bcl-X/efeitos dos fármacos , Intestino Delgado/irrigação sanguínea , Fatores de Tempo , Endotélio Vascular , Distribuição Aleatória , Regulação para Baixo/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes , Resultado do Tratamento , Ratos Wistar , Artéria Mesentérica Superior , Apoptose/efeitos dos fármacos , Constrição , Citoproteção/efeitos dos fármacos , Caspase 1/genética , Proteína bcl-X/genética , Isquemia Mesentérica/prevenção & controle
Acta cir. bras ; 33(11): 983-990, Nov. 2018. graf
Artigo em Inglês | LILACS | ID: biblio-973479


Abstract Purpose: To investigate the efficacy and mechanisms of root tuber of Polygonum ciliinerve (Nakai) ohwi (rPC) which has been used to treat bacterial infection in traditional Chinese medicine. Methods: With the mouse model of Staphylococcus aureus (S. aureus) pneumonia, the phenotype of rPC treated mice, including body weight, mortality, lung slices and bacterial burden were evaluated. Furthermore, inflammatory factors in bronchoalveolar lavage (BAL) were determined by ELISA and the distribution of T cells in lung was assessed by immunofluorescence assay. Results: rPC treatment could dose-dependently reduce weight loss and mortality in S. aureus-infected mice. Upon 10 mg/ml rPC treatment, S. aureus-infected mice showed about 8 grams increase in body weight (P<0.001) and 50% enhancement in mortality. The integrity of lung tissue and bacterial burden were also improved by rPC treatment. Moreover, rPC was found to modulate the immune response in infection. Conclusion: rPC has therapeutic potential for S. aureus infections and pneumonia with immunomodulatory functions.

Animais , Pneumonia Estafilocócica/prevenção & controle , Staphylococcus aureus/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Substâncias Protetoras/farmacologia , Polygonum/química , Imunomodulação/efeitos dos fármacos , Antibacterianos/farmacologia , Pneumonia Estafilocócica/patologia , Pneumonia Estafilocócica/tratamento farmacológico , Fatores de Tempo , Ensaio de Imunoadsorção Enzimática , Líquido da Lavagem Broncoalveolar/química , Imuno-Histoquímica , Contagem de Colônia Microbiana , Reprodutibilidade dos Testes , Interleucina-6/análise , Fator de Necrose Tumoral alfa/análise , Resultado do Tratamento , Quimiocina CCL2/análise , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos Endogâmicos C57BL
Int. j. morphol ; 36(2): 395-401, jun. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-954127


We aimed to evaluate the effects of detorsion and Allium sativum (garlic oil) treatment on the ovarian reserve in an ovarian torsion model. Ovarian torsion may lead to loss of ovarian tissue and infertility. It is an experimental rat study that was carried out on 16 sets of ovaries each, one for treatment group and a control group. In the control group, the procedure involved only the surgically opening and closing the abdomen. Bilateral adnexal torsion/detorsion was performed after a 3-hour ischemia period for the detorsion-only group. The detorsion + Allium sativum group received a 5 ml/kg dose of Allium sativum intraperitoneally, 2 hours before surgery. After the second surgery, removed ovarian samples were evaluated for follicle counts, damage scores and other parameters. Primordial, preantral, small antral and large antral follicle counts were significantly higher in the detorsion + Allium sativum group. Degeneration, congestion, hemorrhage ,inflammation and total damage scores were significantly elevated in the detorsion only group compared to those for the detorsion + Allium sativum group. Finally, there was a significant correlation between AMH alterations and postoperative, preantral follicle count (p<0.05). As a conclusion detorsion + Allium sativum treatment may be effective in protecting the ovarian reserve after torsion.

Intentamos evaluar los efectos de la detorsión y el tratamiento con Allium sativum (aceite de ajo) en la reserva ovárica en un modelo de torsión ovárica. La torsión ovárica puede ocasionar pérdida de tejido ovárico e infertilidad. Este es un estudio experimental en ratas que se llevó a cabo en 16 sets de ovarios para cada grupo: tratamiento y control. En el grupo control, el procedimiento involucró solamente la apertura y el cierre quirúrgicos del abdomen. La torsión / detorsión anexial bilateral se realizó después de un período de isquemia de 3 horas para el grupo de solo detorsión. El grupo de detorsión + Allium sativum recibió una dosis de 5 ml / kg de Allium sativum por vía intraperitoneal, 2 horas antes de la cirugía. Después de la segunda cirugía, las muestras ováricas eliminadas se evaluaron para recuentos de folículos, puntajes de daño y otros parámetros. Los recuentos de folículos antrales primordiales, preantrales, antrales pequeños y grandes fueron significativamente mayores en el grupo con detorsión + Allium sativum. Los puntajes de degeneración, congestión, hemorragia, inflamación y daño total fueron significativamente elevados en el grupo de solo detorsión, en comparación con los del grupo de detorsión + Allium sativum. Finalmente, hubo una correlación significativa entre las alteraciones de AMH y el recuento de folículos preantrales postoperatorios (p <0,05). Como conclusión, el tratamiento con detorsión + Allium sativum puede ser eficaz para proteger la reserva ovárica después de la torsión.

Animais , Feminino , Ratos , Doenças Ovarianas/tratamento farmacológico , Ovário/efeitos dos fármacos , Sulfetos/administração & dosagem , Compostos Alílicos/administração & dosagem , Alho/química , Anormalidade Torcional , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras , Modelos Animais de Doenças , Reserva Ovariana/efeitos dos fármacos
Int. j. morphol ; 36(2): 447-453, jun. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-954135


Although Momordica charantia (MC) has preventive effects on tissue injuries, antioxidant capacity and protective effect of MC pulp and peel (MCP) on valproic acid (VPA)-testicular damage have never been reported. Fresh MCPs were aqueous extracted and determined for antioxidant capacity and momordicine I level by HPLC. Male rats were divided into 5 groups (control, VPA (500 mg/kgBW), MCP20/40/ or 80 mg/kgBW+VPA). In 30 experimental days, animals were pretreated with different doses of MCPs for 20 days before VPA injection for 10 consecutive days. Sperm concentration, testosterone hormone, and testicular histology of all groups were investigated. Expressions of testicular tyrosine phosphorylated and steroidogenic acute regulatory (StAR) proteins were examined by Western blot. Results showed that MCP contains TPC (39.24±0.65 ug/mg garlic acid), antioxidant capacities (FRAP=33.08±0.21 ug/ mg ascorbic acid equivalent, IC50 of DPPH=389.8±3.20 ug/ml), and momordicine I (404.9 mg/g MCP). Sperm concentration in MCP80+VPA group was increased as compared to VPA group. Testosterone level in MCP treated groups was significantly increased. MCP protected testicular damage and could prevent the decrease of StAR and a 50-kDa phosphorylated protein expression in VPAtreated testis. In conclusion, MCP has antioxidant activities and can prevent male reproductive toxicity in VPA-induced rats.

A pesar que la Momordica charantia (MC) tiene efectos preventivos sobre las lesiones en los tejidos, capacidad antioxidante y un efecto protector de la pulpa y la cáscara de MC (CMC) sobre el ácido valproico (AVP), aún no se ha informado efectos sobre el daño testicular. Las CMC frescas fueron extraídas de forma acuosa y se determinó la capacidad antioxidante y el nivel de Momordicina I por HPLC. Las ratas machos se dividieron en 5 grupos: control, AVP (500 mg/kg de peso corporal), CMC20 / 40 / u 80 mg/kg de peso corporal + AVP . En 30 días experimentales, los animales fueron pretratados con diferentes dosis de CMC durante 20 días antes de la inyección de AVP durante 10 días consecutivos. Se investigó la concentración de espermatozoides, la hormona testosterona y la histología testicular de todos los grupos. Las expresiones de proteínas reguladoras agudas (StAR) fosforiladas con tirosina y esteroidogénicas testiculares se examinaron mediante inmunotransferencia de tipo Western. Los resultados mostraron que CMC contiene TPC (39.24 ± 0.65 ug / mg de ácido de ajo), capacidades antioxidantes (FRAP = 33.08 ± 0.21 ug / mg de ácido ascórbico equivalente, IC50 de DPPH = 389.8 ± 3.20 ug / ml) y momordicina I (404.9 mg) / g CMC). La concentración de esperma en el grupo MCP80 + AVP aumentó en comparación con el grupo AVP. El nivel de testosterona en los grupos tratados con CMC aumentó significativamente. La CMC protegió el daño testicular y pudo prevenir la disminución de StAR y una expresión de proteína fosforilada de 50 kDa en los testículos tratados con AVP. En conclusión, la CMC tiene efectos antioxidantes y puede prevenir la toxicidad reproductiva en ratas machos inducidas por VPA.

Animais , Masculino , Ratos , Testículo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Momordica charantia , Antioxidantes/administração & dosagem , Tamanho do Órgão , Fenóis/análise , Espermatozoides/efeitos dos fármacos , Esteróis/análise , Testículo/patologia , Testosterona/análise , Extratos Vegetais/química , Western Blotting , Cromatografia Líquida de Alta Pressão , Ácido Valproico/toxicidade , Ratos Wistar , Substâncias Protetoras , Anticonvulsivantes/toxicidade
Acta cir. bras ; 33(4): 362-374, Apr. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-886283


Abstract Purpose: To investigate the prophylactic and therapeutical effects of sildenafil in a model of acute radiation proctitis (ARP). Methods: All experimental procedures of this study was examined by histopathological, immunohistochemical and transmission electron microscopic analysis. Results: Our histopathological evaluations indicated significant increases in lesion severity, cryptic apsis, cryptitis, cryptic distortion, reactive atypia and infiltration depth of the control (proctitis) group. While the prophylaxis group and the treatment group had significantly lower scores. High-dose group showed similar results as prophylaxis group. Histopathological findings of the prophylaxis group was more significant than the treatment group. Immunoreactivities of IL-1β, FGF-2, TNF- α and HIF-1α increased in the control group especially in the epithelial and cryptic regions. On the contrary, sildenafil application caused significant decreases of inflammatory markers in all treatment groups, specifically better results in the prophylaxis group. Conclusion: The sildenafil has anti-inflammatory effects on ARP, as well as protective effects against ARP and the protective effect of sildenafil surpasses its therapeutic effect histopathologically.

Animais , Proctite/etiologia , Proctite/tratamento farmacológico , Lesões Experimentais por Radiação/tratamento farmacológico , Profilaxia Pós-Exposição/métodos , Citrato de Sildenafila/farmacologia , Anti-Inflamatórios/farmacologia , Proctite/patologia , Lesões Experimentais por Radiação/patologia , Reto/patologia , Fatores de Tempo , Índice de Gravidade de Doença , Imuno-Histoquímica , Distribuição Aleatória , Reprodutibilidade dos Testes , Fator 2 de Crescimento de Fibroblastos/análise , Fator de Necrose Tumoral alfa/análise , Resultado do Tratamento , Substâncias Protetoras/farmacologia , Fator A de Crescimento do Endotélio Vascular/análise , Microscopia Eletrônica de Transmissão , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Interleucina-1beta/análise
Acta cir. bras ; 33(3): 207-215, Mar. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-886274


Abstract Purpose: To investigate whether oxymatrine (OMT) prevents hepatic fibrosis in rats by regulating liver transforming growth factor β1 (TGF-β1) level. Methods: Hepatic fibrosis was induced in rats by thioacetamide (TAA). Blood was collected at the end of week 12 to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and glutathione (GSH). Changes in liver tissue were observed after hematoxylin-eosin (HE) staining. Results: Fibrosis was confirmed by Masson's collagen staining. Liver TGF-β1 level was determined by ELISA. OMT significantly reduced serum ALT and AST but increased GSH levels in rats with hepatic fibrosis. Moreover, it significantly improved liver histology in rats with TAA-induced hepatic fibrosis. It significantly decreased liver TGF-β1 level compared to that in the untreated group. It also significantly reduced collagen deposition in rats. Conclusion: Oxymatrine is effective in protecting rats from thioacetamide-induced hepatic fibrosis by regulating TGF-β1 expression.

Animais , Masculino , Ratos , Quinolizinas/farmacologia , Substâncias Protetoras/farmacologia , Alcaloides/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Cirrose Hepática Experimental/prevenção & controle , Aspartato Aminotransferases/sangue , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/efeitos dos fármacos , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/metabolismo
Braz. J. Pharm. Sci. (Online) ; 54(1): e17529, 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-951902


Abstract The present study aimed to investigate the protective effects of silymarin (SMN), an antioxidant, on methotrexate (MTX)-induced damage in rat testes. Thirty-two Wistar albino rats were divided into four groups (n = 8): control, MTX (20 mg/kg, i.p. on days 1 and 5), SMN (200 mg/kg, orally), and MTX + SMN (20 mg/kg, i.p. on days 1 and 5 and SMN 200 mg/kg orally) groups. At the end of the 6-week trial period, histopathological, immunohistochemical, biochemical, and spermatological analyses were performed on testes tissues. Histopathologically, MTX-induced damage, including depletion of germ cell and loos of spermatozoa, was significantly improved with SMN treatment. Immunohistochemically, the immunoreactivity of glutathione peroxidase 1 (GPx1) and manganese superoxide dismutase 2 (SOD2) were detected more intensely in the MTX + SMN group than in the MTX group. Biochemical examinations revealed that SMN supplementation decreased the lipid peroxidation and increased enzymatic antioxidants in the SMN-treated rats. Spermatologically, significant differences were found in the density, motility, dead-to-live sperm ratio, and abnormal sperm rate in the MTX + SMN group compared to the MTX group. In conclusion, SMN seems to have protective effects as an antioxidant against MTX-induced damage in rat testes.

Animais , Masculino , Ratos , Silimarina/efeitos adversos , Testículo/anormalidades , Substâncias Protetoras/análise , Metotrexato/análise
Acta cir. bras ; 32(11): 949-955, Nov. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-886182


Abstract Purpose: To evaluate the effects of hypertonic saline solution associated to remote ischemic perconditioning in liver ischemia/reperfusion injury in rats. Methods: 25 male rats (Wistar) were distributed into five groups: Sham group (S); Ischemia/Reperfusion group (I/R) with 30 minutes of liver ischemia; Remote ischemic perconditioning group (Per) with three cycles of 10 minutes of I/R performed during liver ischemia; Hypertonic saline solution group (HSS) treated with hypertonic saline solution (4ml/kg); Remote ischemic perconditioning + Hypertonic saline solution group (Per+HSS) with both treatments. Results: Per+HSS group showed a lower degree of liver dysfunction in relation to I/R group, whereas the technique of remote ischemic perconditioning isolated or associated with saline solution significantly improved liver function and reduced histological damage. Conclusion: Remote ischemic perconditioning associated or not to saline solution promoted reduction of acute liver injury induced by ischemia/reperfusion.

Animais , Masculino , Solução Salina Hipertônica/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Precondicionamento Isquêmico/métodos , Substâncias Protetoras/farmacologia , Fígado/irrigação sanguínea , Albumina Sérica/análise , Distribuição Aleatória , Ratos Wistar , Estatísticas não Paramétricas , Modelos Animais de Doenças , Fígado/efeitos dos fármacos
Acta cir. bras ; 32(10): 796-806, Oct. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-886176


Abstract Purpose: To investigate the potential protective effects of erdosteine against the harmful effects of ischemia-reperfusion injury on the liver in an experimental rat model. Methods: Forty rats were divided into 4 groups. In the sham group, only the hepatic pedicle was mobilized. No other manipulation or treatment was performed. In the other groups, ischemia was achieved by clamping the hepatic pedicle for 60 min. After that, 90 min reperfusion was provided. In the control group, no treatment was given. In the perioperative treatment group, 100 mg/kg erdosteine was administered 2 hours before ischemia induction. In the preoperative treatment group, 100 mg/kg/day erdosteine was administered daily for ten days before the operation. At the end of the procedures, blood and liver samples were obtained for biochemical and histopathological assessment. Results: Treatment with erdosteine ameliorated the histopathological abnormalities when compared with the control group. Furthermore, this treatment significantly decreased the serum liver function test values. It was also found that erdosteine ameliorated the oxidative stress parameters in both the perioperative and preoperative treatment groups. Conclusion: The current study is the first to have shown the favorable effects of erdosteine on the harmful effects of experimental hepatic ischemia-reperfusion injury.

Animais , Feminino , Ratos , Tioglicolatos/administração & dosagem , Tiofenos/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Substâncias Protetoras/administração & dosagem , Fígado/irrigação sanguínea , Ratos Wistar , Modelos Animais de Doenças , Fígado/patologia
Acta cir. bras ; 32(10): 873-880, Oct. 2017. graf
Artigo em Inglês | LILACS | ID: biblio-886168


Abstract Purpose: To evaluate the ability of dexamethasone to protect against cisplatin (CDDP)-induced ototoxicity. Methods: Male Wistar rats were divided into the following three groups: 1) Control (C): 6 animals received intraperitoneal (IP) saline solution, 8 ml/kg/day for four days; 2) C + CDDP: 11 animals received 8 ml/kg/day of IP saline and, 90 min after saline administration, 8 mg/kg/day of IP CDDP for four days; and 3) DEXA15 + CDDP: 11 animals received IP dexamethasone 15 mg/kg/day and, 90 min after dexamethasone administration, received 8 mg/kg/day of IP CDDP for four days. Results: It was found that dexamethasone did not protect against weight loss in CDDP-exposed animals. The mortality rate was comparable with that previously reported in the literature. The auditory threshold of animals in the DEXA15 + CDDP group was not significantly altered after exposure to CDDP. The stria vascularis of animals in the DEXA15 + CDDP group was partially preserved after CDDP exposure. Conclusions: Dexamethasone at the dose of 15 mg/kg/day partially protected against CDDP-induced ototoxicity, based on functional evaluation by brainstem evoked response audiontry (BERA) and morphological evaluation by optical microscopy. However, dexamethasone did not protect against systemic toxicity.

Animais , Masculino , Ratos , Limiar Auditivo/efeitos dos fármacos , Dexametasona/uso terapêutico , Cisplatino/toxicidade , Cóclea/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Antineoplásicos/toxicidade , Ratos Wistar , Modelos Animais
Acta cir. bras ; 32(6): 429-439, June 2017. graf
Artigo em Inglês | LILACS | ID: biblio-886202


Abstract Purpose: To determine whether dexmedetomidine (DEX) could attenuate acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) in streptozotocin (STZ)-induced diabetic rats. Methods: Four groups each containing six rats were created (sham control(S), diabetes-sham (DS), diabetes I/R (DI/R), and diabetes-I/R-dexmedetomidine (DI/R-DEX). In diabetes groups, single-dose (65 mg/kg) STZ was administered intraperitoneally (i.p.). In Group DI/R, ischemia reperfusion was produced via 25 min of bilateral renal pedicle clamping followed by 48 h of reperfusion. In Group DI/R-DEX, 50 μg/kg dexmedetomidine was administered intraperitoneally 30 minutes before ischemia. Renal function, histology, apoptosis, the levels of TNF-α, IL-1β, and oxidative stress in diabetic kidney were determined. Moreover, expression of P38 mitogen-activated protein kinase (P38-MAPK), phosphorylated-P38-MAPK(p-P38-MAPK) and thioredoxin-interacting protein (TXNIP) were assessed. Results: The degree of renal I/R injury was significantly increased in DI/R group compared with S group and DS group. The levels of TNF-α, IL-1β, oxidative stress and apoptosis were found significantly higher in DI/R Group when compared with S Group and DS Group. The protein expression of p-P38-MAPK and TXNIP were significantly increased after I/R. All these changes were reversed by DEX treatment. Conclusion: The renoprotective effects of DEX-pretreatment which attenuates I/R-induced AKI were partly through inhibition of P38-MAPK activation and expression of TXINP in diabetic kidney.

Animais , Masculino , Ratos , Traumatismo por Reperfusão/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Dexmedetomidina/uso terapêutico , Diabetes Mellitus Experimental/complicações , Rim/efeitos dos fármacos , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas de Transporte/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Ratos Sprague-Dawley , Estreptozocina , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Rim/lesões , Rim/patologia
Acta cir. bras ; 32(6): 407-417, June 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-886210


Abstract Purpose: To investigate the hepatoprotective and antioxidant effeicacies of Silybum marianum's (silymarin, S) on University of Wisconsin (UW) and histidinetryptophan-ketoglutarate (HTK) preservation solutions. Methods: Thirty two Wistar albino adult male rats were used. Group 1: UW group, Group 2: UW + Silymarin group(S), Group 3: HTK group, Group 4: HTK + silymarin group (S), respectively. Silymarin was enforced intraperitoneally before the surgery. Biopsies were enforced in 0, 6 and 12.hours to investigate. Results: Biochemical parameters examined in alanine aminotransferase (ALT), furthermore superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in rats were also evaluated. Detected histopathological changings were substantially declining in the groups that received silymarin, cellular damage was decreased significantly in HTK + Silymarin group, according to other groups. It has been identified as the most effective group was HTK + silymarin group in evaluation of ALT, electron microscopic results, also decreased MDA and elevated in SOD, and CAT activity. Caspase 3 analysis showed a substantial lower apoptosis ratio in the silymarin groups than in the non-performed groups (p<0.05). Conclusion: Histidinetryptophan-ketoglutarate+silymarin group provides better hepatoprotection than other groups, by decreasing the hepatic pathologic damage, delayed changes that arise under cold ischemic terms.

Animais , Masculino , Ratos , Silimarina/uso terapêutico , Soluções para Preservação de Órgãos , Substâncias Protetoras/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Antioxidantes/uso terapêutico , Cloreto de Potássio , Procaína , Rafinose , Imuno-Histoquímica , Adenosina , Alopurinol , Ratos Wistar , Modelos Animais de Doenças , Glucose , Glutationa , Insulina , Manitol
J. appl. oral sci ; 25(3): 258-264, May-June 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-893623


Abstract Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is able to increase salivary calcium and phosphate levels at an acidic pH. Previous studies demonstrated that a CPP-ACP chewing gum was able to enhance the re-hardening of erosion lesions, but could not diminish enamel hardness loss. Therefore, there is no consensus regarding the effectiveness of CPP-ACP on dental erosion. Objective This in situ study investigated the ability of a CPP-ACP chewing gum in preventing erosive enamel loss. Material and Methods: During three experimental crossover phases (one phase per group) of seven days each, eight volunteers wore palatal devices with human enamel blocks. The groups were: GI - Sugar free chewing gum with CPP-ACP; GII - Conventional sugar free chewing gum; and GIII - No chewing gum (control). Erosive challenge was extraorally performed by immersion of the enamel blocks in cola drink (5 min, 4x/day). After each challenge, in groups CPP and No CPP, volunteers chewed one unit of the corresponding chewing gum for 30 minutes. Quantitative analysis of enamel loss was performed by profilometry (µm). Data were analyzed by Repeated-Measures ANOVA and Tukey's test (p<0.05). Results The use of chewing gum (CPP and No CPP) resulted in lower erosive enamel loss compared with the control group (p<0.05). CPP-ACP chewing gum (CPP) did not improve the protection against erosive enamel loss compared with conventional chewing gum (No CPP) (p>0.05). Conclusion The CPP-ACP chewing gum was not able to enhance the anti-erosive effect of conventional chewing gum against enamel loss.

Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Erosão Dentária/prevenção & controle , Caseínas/uso terapêutico , Goma de Mascar , Substâncias Protetoras/uso terapêutico , Esmalte Dentário/efeitos dos fármacos , Saliva/metabolismo , Remineralização Dentária , Cariostáticos/uso terapêutico , Cariostáticos/farmacologia , Caseínas/farmacologia , Reprodutibilidade dos Testes , Análise de Variância , Resultado do Tratamento , Estatísticas não Paramétricas , Estudos Cross-Over , Substâncias Protetoras/farmacologia , Testes de Dureza
Acta cir. bras ; 32(5): 376-387, May 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-837712


Abstract Purpose: To investigate whether modulating GSK-3β could attenuate myocardial ischemia reperfusion injury (MIRI) induced acute lung injury (ALI) and analyze the underlying mechanism. Methods: Male SD rats were subjected to MIRI with or without myocardial ischemic post-conditioning in the presence or absence of GSK-3β inhibitor. GSK-3β inhibitor was injected peritoneally 10min before MIRI. Lung W/D weight ratio, MPO, PMNs, histopathological changes, TUNEL, Bax, Bcl-2, IL-6, IL-8, IL-10, GSK-3β, and caspase-3 were evaluated in the lung tissues of all rats. Results: After MIRI, lung injury was significantly increased manifested as significant morphological changes and increased leukocytes in the interstitial capillaries, Lung W/D ratio, MPO, and PMN in BALF, which was associated with enhanced inflammation evidenced by increased expressions of IL-6, IL-8 and reduced expression of IL-10. MIRI significantly increased cell apoptosis in the lung as increased levels of apoptotosis, Bax, cleaved caspase-3, and reduced expression of Bcl-2 was observed, which was concomitant with reduced p-GSK-3β. All these changes were reversed/prevented by ischemic post-conditioning, while these beneficial effects of ischemic post-conditioning were abolished by GSK-3β inhibition. Conclusion: Myocardial ischemia reperfusion injury induces acute lung injury by induction of inflammation and cell apoptosis. Ischemic post-conditioning protects the lung from ALI following MIRI by increasing p-GSK-3β.

Animais , Masculino , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Substâncias Protetoras/metabolismo , Lesão Pulmonar Aguda/prevenção & controle , Pós-Condicionamento Isquêmico/métodos , Glicogênio Sintase Quinase 3 beta/metabolismo , Distribuição Aleatória , Regulação para Baixo , Interleucinas/metabolismo , Ratos Sprague-Dawley , Apoptose/efeitos dos fármacos , Peroxidase/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Substâncias Protetoras/farmacologia , Marcação In Situ das Extremidades Cortadas , Modelos Animais , Ativação Enzimática , Proteína X Associada a bcl-2/metabolismo , Caspase 3/metabolismo , Lesão Pulmonar Aguda/enzimologia , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta/farmacologia , Inflamação/metabolismo , Infarto do Miocárdio/patologia , Neutrófilos/enzimologia