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Non-alcoholic fatty liver is the leading cause of hepatic disease worldwide and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) due to cell injury, oxidative stress, and apoptosis. The kinins' role in the liver has been studied in experimental fibrosis, partial hepatectomy, and ischemia-reperfusion and is related to cell death and regeneration. We investigated its role in experimental NASH induced by a methionine-choline deficient diet for 4 weeks. After that, liver perfusion was performed, and bradykinin (BK) or des-Arg9-BK was infused. Cell death was evaluated by cathepsin-B and caspase-3 activity and oxidative stress by catalase (CAT), glutathione S-transferase, and superoxide dismutase (SOD) activities, as well as malondialdehyde and carbonylated proteins. In control livers, DABK increased CAT activity, which was reversed by antagonist DALBK. In the NASH group, kinins tend to decrease antioxidant activity, with SOD activity being significantly reduced by BK and DABK. Malondialdehyde levels increased in all NASH groups, but carbonylated protein did not. DABK significantly decreased cathepsin-B in the NASH group, while caspase-3 was increased by BK in control animals. Our results suggest that B1R and/or B2R activation did not induce oxidative stress but affected the antioxidant system, reducing SOD in the NASH group.
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Photobiomodulation (PBM) has therapeutic effects on wound healing, diabetic microangiopathy, and retinopathy. However, little is known about the use of PBM for the treatment of diabetes mellitus (DM). In this context, we aimed to evaluate the effects of PBM on pancreas morphology and insulin and glucose tolerance in an experimental model of DM. Thus, DM was induced by streptozotocin (STZ) (60 mg/kg). Subsequently, the rats were treated with PBM (808 nm and 30 J/cm2 ). After euthanasia, morphometric parameters and immunoreactivity for insulin and 8-OHdG were evaluated in the pancreas. The results showed that treated animals had higher values of body mass and higher values in the number of beta cells in the pancreas. In conclusion, PBM resulted in decreased weight loss in STZ-induced diabetic rats and presented a stimulatory effect on the pancreas of the treated animals, highlighting the promising effects of this therapy in the clinical condition of DM.
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Diabetes Mellitus Experimental , Insulinas , Terapia com Luz de Baixa Intensidade , Ratos , Animais , Ratos Wistar , Terapia com Luz de Baixa Intensidade/métodos , Pâncreas , Homeostase , Insulinas/uso terapêutico , Glucose , Glicemia , Insulina/uso terapêuticoRESUMO
BACKGROUND/AIM: It has been shown that the methionine-choline deficient (MCD) diet induces hepatocarcinogenesis, but not in extrahepatic organs, such as the testis, and pancreas, although may increase chemical-induced carcinogenesis in the colon, mammary gland, esophagus, and pancreas. Accumulating evidence suggests that salivary glands are very susceptible to stress conditions, such as radiation, hyperglycemia, and exposure to xenobiotics in vivo. This study aimed to analyze the histological changes on the major salivary glands (parotid, submandibular, and sublingual) after MCD diet administration. MATERIALS AND METHODS: Male Swiss mice were submitted to ad libitum access to the control (AIN-76) or MCD diet for 28 days. The rebound group received the MCD diet for 24 days and the control diet for 10 days. Using the AxioImager A2 microscope, the hematoxylin-eosin (HE) stained specimens (4 mm) were evaluated for tissue degeneration, nuclear hyperchromatism and atrophy. RESULTS: In the parotid gland from the MCD group, tissue degeneration, pyknosis, apoptosis and atrophy were observed, which remained in the rebound group, associated with hyperchromatism. In the submandibular gland from both MCD and rebound groups, severe tissue disorganization was associated with cell pleomorphism, hyperchromatic cells, apoptosis, increased eosinophilia, and inflammatory infiltrate. Finally, in the sublingual gland, there were no histological alterations in the experimental groups compared to the control. CONCLUSION: MCD can induce pre-neoplastic changes in the mouse parotid and submandibular glands, which are not reversed by a change in the diet.
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Colina , Metionina , Animais , Atrofia/patologia , Dieta , Masculino , Camundongos , Racemetionina , Glândulas Salivares/patologiaRESUMO
To evaluate, through a systematic review, the assessment of genotoxicity of glass ionomer cements in vitro and in vivo. A systematic review was performed with the problem, intervention, control, and outcomes (PICOS) strategy, aiming to answer the following question: "Can glass ionomer cements induce genetic damage in vitro and in vivo?" A systematic search was performed in the following electronic databases: PubMed (including MedLine), Web of Science, and Scopus. The quality of included studies was assessed using the Effective Public Health Practice Project (EPHPP). After the authors performed the review of all articles, a total of 13 manuscripts met all the inclusion criteria in the systematic review. Following the parameters of the EPHPP, eight articles were classified as strong or moderate quality. The other ones (five studies) were weak. Taken together our results demonstrated that, six studies reported genotoxicity of the modified glass ionomer cements tested and two studies concluded that the effect of genotoxicity was time dependent.
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Dano ao DNA , Cimentos de Ionômeros de Vidro , Cimentos de Ionômeros de Vidro/toxicidadeRESUMO
This systematic review (SR) with meta-analysis aimed to evaluate the scientific data related to cytogenetic damage in oral exfoliated cells of patients diagnosed with oral potentially malignant disorders (OPMDs). The SR was conducted according to the PRISMA-P guidelines. The PICOS (Participants, Intervention, Comparison, Outcome, and Study Design) strategy was used to answer the question: "Is micronucleus assay in oral exfoliated cells a suitable biomarker for predicting cancer risk in individuals with OPMDs?" The search strategy was performed in the following electronic databases: PubMed, Medline, Scopus and Web of Science. The comparisons were defined as standardized mean difference (SMD), and 95% confidence intervals (CI). The quality of included studies was assessed using the EPHPP (Effective Public Health Practice Project). The GRADE tool was also utilized to assess the quality of evidence of the SR. A total of 110 potentially relevant studies were selected through the search strategy. After screening titles and abstracts, 20 full-text manuscripts were assessed for eligibility and three observational studies were included in the meta-analysis. After reviewing the 20 studies, 13 were considered weak. The meta-analysis data revealed a statistically significant difference in oral micronucleated cells by patients with OPMDs when compared to control (SMD=1.77, 95% CI, 0.36-3.18, p = 0.01), with a Tau2 = 1.97; Chi2 = 66.64, and p < 0.001. Patients with OPMDs had a positive response related to mutagenicity in oral cells compared to control patients. However, SR was not able to validate the micronucleus assay as a putative biomarker in individuals with oral potentially malignant disorders since the majority of studies were considered weak based on high risk of bias.
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Neoplasias Bucais , Lesões Pré-Cancerosas , Biomarcadores , Humanos , Testes para MicronúcleosRESUMO
Lactulose is a nonabsorbable disaccharide commonly used in clinical practice to treat hepatic encephalopathy. However, its effects on neuropsychiatric disorders and motor behavior have not been fully elucidated. Male Wistar rats were bile-duct ligated, and 3 weeks after surgery, treated with lactulose administrated by gavage (1.43 or 3.57 g/kg), once a day for seven days. Plasma levels of ammonia, aspartate aminotransferase, total bilirubin, and creatinine were quantified and histopathological analysis of the livers was performed. Locomotor activity measurements were performed in an open field. The expression of water channel aquaporin-4 was investigated and the analysis of Fos protein immunoreactivity was used to evaluate the pattern of neural activation in brain areas related to motor behavior. Bile-duct ligated rats showed hyperammonemia, loss of liver integrity and function, impaired locomotor activity, reduced aquaporin-4 protein expression, and neuronal hyperactivity. Lactulose treatment was able to reduce ammonia plasma levels, despite not having an effect on biochemical parameters of liver function, such as aspartate aminotransferase activity and total bilirubin levels, or on the cirrhotic hepatic architecture. Lactulose was also able to reduce the locomotor activity impairments and to mitigate or reverse most changes in neuronal activation. Lactulose had no effect on reduced aquaporin-4 protein expression. Our findings confirm the effectiveness of lactulose in reducing hyperammonemia and neuronal hyperactivity in brain areas related to motor behavior, reinforcing the importance of its clinical use in the treatment of the symptoms of cirrhosis-associated encephalopathy.
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Comportamento Animal/efeitos dos fármacos , Hiperamonemia/tratamento farmacológico , Lactulose/farmacologia , Fígado/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Amônia/sangue , Animais , Aquaporina 4/metabolismo , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Creatinina/sangue , Modelos Animais de Doenças , Hiperamonemia/metabolismo , Hiperamonemia/patologia , Lactulose/uso terapêutico , Fígado/metabolismo , Fígado/patologia , Masculino , Neurônios/metabolismo , Neurônios/patologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos WistarRESUMO
AIM: To study hepatic vasoconstriction and glucose release induced by angiotensin (Ang)II or Epi in rats with pharmacological hypertension and spontaneously hypertensive rat (SHR). METHODS: Isolated liver perfusion was performed following portal vein and vena cava cannulation; AngII or epinephrine (Epi) was injected in bolus and portal pressure monitored; glucose release was measured in perfusate aliquots. RESULTS: The portal hypertensive response (PHR) and the glucose release induced by AngII of L-NAME were similar to normal rats (WIS). On the other hand, the PHR induced by Epi in L-NAME was higher whereas the glucose release was lower compared to WIS. Despite the similar glycogen content, glucose release induced by AngII was lower in SHR compared to Wistar-Kyoto rats although both PHR and glucose release induced by Epi in were similar. CONCLUSION: AngII and Epi responses are altered in different ways in these hypertension models. Our results suggest that inhibition of NO production seems to be involved in the hepatic effects induced by Epi but not by AngII; the diminished glucose release induced by AngII in SHR is not related to glycogen content.
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OBJECTIVE: The present study aimed to evaluate the in vivo response of a resistance training and low-level laser therapy (LLLT) on tibias and femurs of rats with diabetes mellitus (DM). MATERIALS AND METHODS: Forty male Wistar rats were randomly distributed into four experimental groups: control group (CG), diabetic group (DG), diabetic trained group (TG) and diabetic trained and laser irradiated group (TLG). DM was induced by streptozotocin (STZ) and after two weeks laser and resistance training started, performed for 24 sessions, during eight weeks. At the end of the experiment, animals were euthanized and tibias and femurs were removed for analysis. Histological, histomorphometrical, immunohistochemistry and mechanical analyses were performed. RESULTS: Trained groups, with or without laser irradiation, showed increased cortical area, bone density and biomechanical properties. The immunohistochemical analysis revealed that TG and TLG demonstrated an increased RUNX2 expression. RANK-L immunoexpression was similar for all experimental groups. CONCLUSION: In conclusion, it can be suggested that the resistance exercise program stimulated bone metabolism, culminating in increased cortical tibial area, bone mineral content, bone mineral density and biomechanical properties. Furthermore, the association of physical exercises and LLLT produced higher values for bone mineral content and stiffness. Consequently, these data highlight the potential of physical exercise in the management of bone loss due to DM and the possible extra osteogenic stimulus offered by lasertherapy. Further long-term studies should be carried out to provide additional information.
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Diabetes Mellitus/fisiopatologia , Fêmur/fisiologia , Fêmur/efeitos da radiação , Terapia com Luz de Baixa Intensidade/métodos , Treinamento Resistido/métodos , Tíbia/fisiologia , Tíbia/efeitos da radiação , Animais , Glicemia/análise , Densidade Óssea/fisiologia , Densidade Óssea/efeitos da radiação , Doenças Ósseas Metabólicas/fisiopatologia , Doenças Ósseas Metabólicas/prevenção & controle , Densitometria/métodos , Diabetes Mellitus/prevenção & controle , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Experimental/prevenção & controle , Imuno-Histoquímica , Masculino , Ligante RANK/análise , Distribuição Aleatória , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Estreptozocina , Fatores de Tempo , Resultado do TratamentoRESUMO
ABSTRACT Objective The present study aimed to evaluate the in vivo response of a resistance training and low-level laser therapy (LLLT) on tibias and femurs of rats with diabetes mellitus (DM). Materials and methods Forty male Wistar rats were randomly distributed into four experimental groups: control group (CG), diabetic group (DG), diabetic trained group (TG) and diabetic trained and laser irradiated group (TLG). DM was induced by streptozotocin (STZ) and after two weeks laser and resistance training started, performed for 24 sessions, during eight weeks. At the end of the experiment, animals were euthanized and tibias and femurs were removed for analysis. Histological, histomorphometrical, immunohistochemistry and mechanical analyses were performed. Results Trained groups, with or without laser irradiation, showed increased cortical area, bone density and biomechanical properties. The immunohistochemical analysis revealed that TG and TLG demonstrated an increased RUNX2 expression. RANK-L immunoexpression was similar for all experimental groups. Conclusion In conclusion, it can be suggested that the resistance exercise program stimulated bone metabolism, culminating in increased cortical tibial area, bone mineral content, bone mineral density and biomechanical properties. Furthermore, the association of physical exercises and LLLT produced higher values for bone mineral content and stiffness. Consequently, these data highlight the potential of physical exercise in the management of bone loss due to DM and the possible extra osteogenic stimulus offered by lasertherapy. Further long-term studies should be carried out to provide additional information.