Navegando por Palavras-chave "Chondroitin Sulfate"

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    Efeito Do Condroitim Sulfato Na Fibrogênese Hepática Induzida Por Ligadura Do Ducto Biliar Em Ratos
    (Universidade Federal de São Paulo (UNIFESP), 2017-10-26) Guedes, Pedro Luiz Rodrigues [UNIFESP]; Nagaoka, Márcia Regina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Background and Aims: One of the many causes of hepatic fibrosis is cholestasis, which causes cell death and triggers cytokines and chemokines release, leading to leukocyte infiltration and extracellular matrix deposition. The current treatment of hepatic fibrosis is based on withdrawal of the causing agent, so the investigation of new and effective strategies for the treatment of liver fibrosis is very important. Many studies highlight the action of chondroitin sulfate (CS) in different cell types, leading to the reduction of cytokines expression. The aim of this work was to analyze effects of CS on experimental model of extra-hepatic cholestasis induced by common bile duct ligation (BDL). Methods: Wistar rats (6-8 weeks) were submitted to BDL, treated with CS (120 mg/kg body) or vehicle for 1, 2, 7, 14, 21 or 28 days intraperitoneally, and then euthanized; sham animals were used as control. We analyzed serum alanine and aspartate aminotransferases (ALT and AST, respectively) activities and performed histomorphometric analysis on Picrosirius-stained liver specimens using the Axiovision software. To analyze cell death and inflammation, caspase-3 and cathepsin B activities on liver homogenates were measured using fluorometric substrates Ac-DEVD-AMC and Abz-GIVRAK(Dnp)-OH, respectively. Apoptosis was also evaluated by TUNEL assay and liver regeneration by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) using monoclonal primary anti-PCNA antibody. Statistical analysis of standardized values was performed by one-way ANOVA with Tukey’s post-hoc. Results are expressed by mean±SEM. Results: BDL rats presented ALT and AST serum activities 2-3 times greater than sham. BDL led to progressive fibrotic septa development, which was confirmed by measuring collagen content (% field) after 7 (11±1, n = 7), 14 (14±1, n = 10), 21 (23±1, n = 4) and 28 (34±3, n = 7) days of induction, while sham group preserved normal liver architecture. CS treatment reduced collagen content on BDL group after 21 days (14±1, n = 6) and significantly (p<0.0001) after 28 days (16±2, n = 6). There were no significant changes on cathepsin B activities of all studied groups. We verified increasing caspase-3 activity (fold sham) on BDL 2d (1.4±0.1, n = 5), 7d (2.2±0.6, n = 7) and 14d (3.3 ± 0.5, n = 10; ANOVA, p < 0.001) when compared to the respective sham groups. Interestingly, CS reduced significantly (p=0.043) the caspase-3 activity after 14 days of treatment (1,7 ±0.7, n = 9) when compared to BDL 14d group. BDL animals had a higher number of apoptotic cells per field (% of total) at 14d (0.58±0.04) than those at 7 (0.25±0.02), 21 (0.33±0.02)and 28 days groups (0.29±0.01). Treatment with CS reduced significantly (p = 0.030) the number of apoptotic cells in the 14d group (0.43±0.04). In addition, BDL led to an increase in the relative amount (% of total) of PCNA-labeled epithelial biliary cells and hepatocytes. Treatment with CS led increased amounts of marked hepatocytes at 14d (2.9±0.1 – ANOVA; p = 0.003) and 21d (3.5±0.2 - ANOVA; p < 0.001) when compared to non-treated groups (2.1±0.1 and 2.2±0.2 respectively). Conclusions: This work shows that CS may reduce first signs of apoptosis, slow down development of liver fibrosis and therefore cirrhosis, besides promoting liver regeneration on experimental model of common bile duct ligation.
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    Efeitos Da Fotobiomodulação E Dos Sulfatos De Glicosamina E Condroitina (Associados Ou Não) Na Cartilagem Articular Em Um Modelo Experimental De Osteoartrite Em Ratos
    (Universidade Federal de São Paulo (UNIFESP), 2017-09-01) Barros, Marcella Sanches Paes De [UNIFESP]; Renno, Ana Claudia Muniz [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Osteoarthritis (OA) is a degenerative joint disease prevalent in the elderly population and is most frequent in the knee joint. Currently, the therapeutic potential of photobiomodulation (FBM) and chondroprotectors, such as the glucosamine and chondroitin sulfates, is highlighted in the treatment of degenerative diseases affecting the joint cartilage. However there is no evidence of concomitant use of these treatments and what the possible interaction between them. Thus, the hypothesis supported was that the association of glucosamine and chondroitin sulfates to FBM may constitute a more effective therapeutic intervention to reduce morphological alterations in the joint cartilage associated with OA. In this way, the objective of this study was to evaluate the effects of FBM and glucosamine and chondroitin sulfates, associated or not, on the rat knee joint cartilage in an experimental model of OA by transection of the anterior cruciate ligament (TLCA). 43 male Wistar rats, separated into 5 groups: Control without lesion (GC); Control model of osteoarthritis - OA without treatment (OA); Model of OA and submitted to the FBM (OAL); Model of OA and treated with the combination of glucosamine and chondroitin sulfates (OAS); Model of OA, submitted to FBM and treated with glucosamine and chondroitin sulfates (OASL). The treatment started 48 hours after surgery for 29 consecutive days. A combination of glucosamine sulfate (500 mg/kg) and chondroitin sulfate (400 mg/kg), and FBM (AsGaAl, continuous = λ=808 nm, P=50 mW, beam area=0.028 cm 2, t= 28s, D=50 J/cm2; = 1.4 J, irradiance=17.8 mW/cm2) at 2 points of the left pelvic limb (lateral and medial face joint). The animals were euthanized 31 days after the surgical procedure. In order to evaluate and compare the effects of the treatments, qualitative histological analyzes were performed using the International Society of OA (OARSI) criteria, morphometric thickness and chondrocyte density, as well as analysis of the expression of Interleukin 1β (IL-1β) and 10 (IL-10), and type II collagen. The results of the present study showed that all treated groups presented better structural organization of joint cartilage and reduction of chondrocyte density. In addition, the OAS and OASL groups presented lower values in OARSI when compared to the other groups. Moreover, the OASL group showed a reduction in IL- 1β immunoexpression and an increase in the immunoexpression of IL-10 and type II collagen when compared to OA. Therefore, we can conclude that the glucosamine sulfate and chondroitin sulfate compound were effective in preventing cartilage degeneration, as well as its association with FBM promoted positive effects in the expression of factors related to the inflammatory process in the experimental model used.
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    Farmacocinética da associação de glucosamina e sulfato de condroitina em humanos sadios do sexo masculino
    (Sociedade Brasileira de Ortopedia e Traumatologia, 2005-01-01) Toffoletto, Odaly; Tavares, Agostinho [UNIFESP]; Casarini, Dulce Elena [UNIFESP]; Redublo, Beata Marie [UNIFESP]; Ribeiro, Artur Beltrame [UNIFESP]; Fundação Oswaldo Ramos Hospital do Rim e Hipertensão; Universidade Federal de São Paulo (UNIFESP)
    Osteoarthrosis is a chronic joint disease that, once patent, leads to a progressive functional disability. As proteochondroitin sulfates are the major contents of the cartilage, it is expected that the ingestion of glucosamine and chondroitin might improve the biological status of that tissue. As we could not find any studies on the pharmacokinetic profile of this association by oral administration route in human beings, the objective of this study was to evaluate it by using the association of glucosamine sulfate (GS) and chondroitin sulfate (CS) given to two groups of twelve healthy male volunteers (group I: one capsule containing 500 mg of GS and 400 mg of CS; group II: four capsules with the same content). Blood samples were collected at pre-determined time intervals up to 48 hours post-dosing. GS and CS were measured in plasma by the DMMB (1,9,dimethyl-dimethilene blue) method. Maximum concentration was achieved within 2 hours (average ± SE; 0.893±0.093 µg/ml, group I; and 2.222±0.313 µg/ml, group II). Areas under curve up to 48 hours were 10.803±0.965 µg-hr/ml and 38.776±2.981 µg-hr/ml for groups I and II, respectively. Both groups showed a second peak after 18 hours, indicating an enterohepatic flow. Our results indicate that this association is absorbed through the oral route by a saturable mechanism, which can enable its use in clinical treatments.
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    Glucosamine and chondroitin sulfate association increases tibial epiphyseal growth plate proliferation and bone formation in ovariectomized rats
    (Hospital Clinicas, Univ São Paulo, 2014-01-01) Wolff, Roberta Bastos; Universidade Federal de São Paulo (UNIFESP)
    OBJECTIVE: the growth plate consists of organized hyaline cartilage and serves as a scaffold for endochondral ossification, a process that mediates longitudinal bone growth. Based on evidence showing that the oral administration of glucosamine sulfate (GS) and/or chondroitin sulfate (CS) is clinically valuable for the treatment of compromised articular cartilage, the current study evaluated the effects of these molecules on the tibial epiphyseal growth plate in female rats.METHOD: the animals were divided into two control groups, including vehicle treatment for 45 days (GC45) and 60 days (GC60) and six ovariectomized (OVX) groups, including vehicle treatment for 45 days (GV45), GS for 45 days (GE45GS), GS+CS for 45 days (GE45GS+CS), vehicle for 60 days (GV60), GS for 60 days (GE60GS) and GS+CS for 60 days (GE60GS+CS). At the end of treatment, the tibias were dissected, decalcified and processed for paraffin embedding. Morphological and morphometric methods were employed for analyzing the distal tibial growth plates using picrosirius red staining and the samples were processed for histochemical hyaluronan detection. Morphometric analyses were performed using the 6.0ProPlus (R) Image system.RESULTS: Notably, after 60 days of treatment, the number of proliferative chondrocytes increased two-fold, the percentage of remaining cartilage increased four-fold and the percentage of trabecular bone increased threefold in comparison to the control animals.CONCLUSION: GS and CS treatment drugs led to marked cellular proliferation of the growth plate and bone formation, showing that drug targeting of the tibial epiphyseal growth plate promoted longitudinal bone growth.