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1.
Nutrients ; 13(7)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34371877

RESUMO

Pathological mechanisms underlining diabetic bone defects include oxidative damage and insulin/IGF-1 imbalance. Morin is a bioflavonoid with antioxidant and anti-diabetic effects. This study evaluates morin's protective effects against altered bone histomorphometry in diabetic rats through assessing insulin/IGF-1 pathway as a potential mechanism. Diabetic animals were administered two morin doses (15 and 30 mg/kg) for 5 weeks. Different serum hepatic and renal functions tests were assessed. Bone density and histomorphometry in cortical and trabecular tissues were evaluated histologically. The expressions of insulin, c-peptide and IGF-1 were estimated. In addition, the enzymatic activities of the major antioxidant enzymes were determined. Diabetic-associated alterations in serum glucose, aminotransferases, urea and creatinine were attenuated by morin. Diabetic bone cortical and trabecular histomorphometry were impaired with increased fibrosis, osteoclastic functions, osteoid formation and reduced mineralization, which was reversed by morin; particularly the 30 mg/kg dose. Insulin/IGF-1 levels were diminished in diabetic animals, while morin treatment enhanced their levels significantly. Diabetes also triggered systemic oxidative stress noticeably. The higher dose (30 mg/kg) of morin corrected the endogenous antioxidant enzymatic activities in diabetic rats. Findings indicate the potential value of morin supplementation against hyperglycemia-induced skeletal impairments. Activation of insulin/IGF-1 signaling could be the underlining mechanism behind these effects.


Assuntos
Antioxidantes/farmacologia , Glicemia/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Fêmur/efeitos dos fármacos , Flavonoides/farmacologia , Hipoglicemiantes/farmacologia , Fator de Crescimento Insulin-Like I/metabolismo , Insulina/sangue , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/patologia , Fêmur/metabolismo , Fêmur/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Transdução de Sinais , Estreptozocina
2.
J Periodontal Res ; 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34363706

RESUMO

OBJECTIVES: This study aimed to evaluate the effect of habitual caffeine (CAF) intake on stability, bone regeneration, and expression of bone markers at the bone-implant interface. BACKGROUND: Studies show that habitual CAF alters bone health and remodeling. Yet, there is no information regarding CAF effects on osseointegration of bone-anchored implants. METHODS: Wistar rats were divided into two groups: one received tap drinking water alone (control) and the other received tap water with CAF (300 mg/L). After 12 weeks, their tibiae received screw-shaped titanium implants. After another 12 weeks, CAF (n = 5) and control (n = 5) animals were sacrificed and the implant stability was evaluated using a removal torque (RTQ) device. Thereafter, the implants were processed for gene expression analysis, and the implantation sites were harvested for histology. Implants with the surrounding bone were dissected en bloc and subjected to micro-computed tomography (micro-CT). RESULTS: The results showed that implants in the CAF group had an 87% significant increase in RTQ compared to the control. Further, micro-CT revealed a higher proportion of mineralized bone filling the implant threads in the CAF group. The molecular analysis indicated higher expression of bone formation (ALP), remodeling (CatK), and vascularization (VEGF) genes in implant-adherent cells in the CAF group. Histology suggested increased vascularity in the tissue surrounding the implant in the CAF group. CONCLUSIONS: Within the limit of this study, it is concluded that habitual CAF intake conveys a positive, promoting effect on long-term osseointegration. Clinical studies are worth pursuing to verify this experimental observation.

3.
Biomed Res Int ; 2021: 5518195, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33954171

RESUMO

The incidence of periodontal diseases is associated with multiple comorbidities that influence a patient's treatment planning. This study evaluates the relation between periodontal disease and multiple comorbidities reported in the Saudi population from the Eastern province. This study was conducted on 190 patients, who visited the periodontology clinics at Imam Abdulrahman Bin Faisal University, Saudi Arabia. Demographic data, smoking habits, past medical and dental histories, blood pressure, random blood glucose, and recent haemoglobin A1c were recorded. A comprehensive periodontal examination included the number of missing teeth, pocket depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and mobility of all teeth except third molars. Radiographic bone loss was measured on standardized full-mouth periapical radiographs. Multivariable regression models were calculated aiming to see the association between different comorbidities and alveolar bone loss with confounders controlled. Out of 190 periodontitis patients, 56 (29.5%) were males and 134 (70.5%) were females. More than half of the patients (60%) were between 26 and 50 years, 30% of them had diabetes, and 18% were smokers. The risk of alveolar bone loss was higher in persons who had diabetes and those who had both diabetes and coronary heart disease than those who did not, although the association was not statistically significant (B = 1.26, 95%CI = -0.30, 2.82, and B = 2.86, 95%CI = -1.25, 6.96, respectively). The risk of alveolar bone loss was significantly higher among persons with diabetes and hypertension (B = 2.82 and 95%CI = 0.89, 4.75). Collectively, the risk of alveolar bone loss in periodontitis patients increases with diabetes in the presence of other comorbidities regardless of smoking or gender.


Assuntos
Doenças Periodontais/epidemiologia , Adolescente , Adulto , Perda do Osso Alveolar/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Arábia Saudita/epidemiologia , Fumar/epidemiologia , Adulto Jovem
4.
Redox Rep ; 25(1): 51-58, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32396454

RESUMO

ABSTRACTObjectives: This study explores the protective role of losartan (LT) against oxidative and inflammatory damages in different physiological systems including heart, liver, and kidney tissue in hypercholesterolemic rats.Methods: After induction of hypercholesterolemia by high cholesterol diet for 6 weeks, LT was administered for 4 weeks. In serum, the levels of lipoproteins, aminotransferases, creatine kinases, urea, apoptosis, and inflammatory markers were measured. In cardiac, hepatic, and renal tissues, lipid peroxidation product and GSH as well as antioxidant enzymatic activities were assayed. Finally, histopathological assessment evaluated the structural damage in cardiac, hepatic, and renal tissues.Results: Serum markers of cardiac, hepatic, and renal toxicities including creatine kinases, aminotransferases, and urea were attenuated by LT in hypercholesterolemic animals. Moreover, LT markedly corrected the elevated levels of lipoproteins, apoptosis, and inflammatory biomarkers. Hypercholesterolemia-induced lipid peroxidation, low GSH levels, and diminished activities of antioxidant enzymes were prominently improved in LT treated animals. Histopathological alterations by hypercholesterolemia in heart, liver, and kidney tissues were ameliorated by LT.Conclusion: This study confirmed the pathological enrollment of renin-angiotensin system in hypercholesterolemia-associated metabolic alterations. LT had a significant cardiac, hepatic, and renal protective role against these impairments through down-regulation of oxidative damage, inflammation and necrosis.


Assuntos
Anti-Hipertensivos/farmacologia , Colesterol na Dieta/toxicidade , Hipercolesterolemia/complicações , Inflamação/tratamento farmacológico , Losartan/farmacologia , Estresse Oxidativo , Sistema Renina-Angiotensina/efeitos dos fármacos , Animais , Hipercolesterolemia/induzido quimicamente , Hipercolesterolemia/patologia , Inflamação/etiologia , Inflamação/patologia , Masculino , Ratos , Ratos Wistar
5.
Med Princ Pract ; 28(2): 178-185, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30537701

RESUMO

OBJECTIVE: Diabetic complications involve multiple pathological pathways, including hyperglycemia-induced oxidative stress and inflammation. Combination therapy is usually employed to improve treatment outcomes and to lower potential adverse effects. In this study, we evaluated the effects of antidiabetic and antihypertensive agents, glibenclamide (GLI) and losartan (LT), on diabetes mellitus (DM)-associated metabolic changes in rats. MATERIALS AND METHODS: Streptozotocin-induced diabetic animals were orally treated with GLI 5 mg/kg and/or LT 25 mg/kg for 4 weeks. Blood glucose, insulin, aspartate aminotransferase, alanine aminotransferase, urinary creatinine, and urea levels were measured. Serum, liver, and kidney values of inflammatory markers, such as interleukin-1ß, tumor necrosis factor alpha, and interleukin-6 were assessed, along with lipid peroxidation products (e.g., thiobarbituric acid reactive substances), endogenous antioxidants (e.g., glutathione), as well as antioxidant enzyme activities (e.g., catalase, superoxide dismutase, and glutathione peroxidase). Finally, histological changes in liver and kidney tissues were evaluated. RESULTS: DM markedly induced systemic, hepatic, and renal inflammation and lowered antioxidant defense mechanisms. Treatment of diabetic rats with either GLI or LT significantly improved liver and kidney functions and histological structure. Moreover, both medications reduced signs of oxidative stress and inflammation in blood, liver, and kidney samples. Combining GLI and LT showed similar protective potential against systemic, hepatic, and renal oxidative stress and inflammation. CONCLUSION: Adding LT to GLI therapy revealed prospective antioxidant and anti-inflammatory action, while no synergistic or additive effects were observed.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Glibureto/farmacologia , Hipoglicemiantes/farmacologia , Losartan/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Glutationa Redutase/efeitos dos fármacos , Estudos Prospectivos , Ratos , Superóxido Dismutase/metabolismo
6.
Biomed Pharmacother ; 97: 1303-1310, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29156519

RESUMO

Estrogen deficiency following menopausal provokes alveolar bone loss, remodeling and inflammation. Eugenol is a phenolic compound with wide dental applications and anti-inflammatory properties. In the present study, the potential protective role of eugenol against alveolar bone deformities was investigated in an ovariectomized (OVX) rodent model. Two doses of eugenol (2.5 and 5 mg/kg/d) were administered to OVX animals for 12 weeks. In Serum, markers of bone metabolism and pro-inflammatory cytokines were estimated using ELISA. Alveolar bone morphometry was analyzed using high-resolution micro-computed tomography (CT). Bone histological analysis (H&E stain) was also performed. Alveolar bone expression of osteoclastogenesis modulating factors, such as osteoprotegerin (OPG), receptor activator of nuclear factor kappa-b ligand (RANKL) and inflammatory mediators, were measured using immunohistochemistry. Eugenol failed to correct elevated body weights and uterine atrophy in OVX rats. The significant elevation of bone metabolic markers and inflammatory cytokines in OVX animals were markedly improved by eugenol treatment, particularly the higher dose. Eugenol treatment considerably attenuated morphometric trabecular alterations of the alveolar bone and improved alveolar resorption and gingival infiltration. Alveolar bone of OVX animals showed augmented expression of RANKL, OPG and inflammatory cytokines, which were corrected by eugenol treatment. Alveolar bone loss and remodeling associated with estrogen insufficiency was ameliorated by eugenol owing to its anti-inflammatory properties, suggesting an extra dental impact for eugenol.


Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Osso e Ossos/efeitos dos fármacos , Eugenol/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Estrogênios/deficiência , Eugenol/administração & dosagem , Feminino , Mediadores da Inflamação/metabolismo , Menopausa , Ovariectomia , Ratos , Ratos Wistar , Microtomografia por Raio-X
7.
Sci Rep ; 7(1): 2293, 2017 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-28536469

RESUMO

The local and systemic renin angiotensin system (RAS) influences the skeletal system micro-structure and metabolism. Studies suggested angiotensin 1-7 (Ang(1-7)) as the beneficial RAS molecule via Mas receptor activation. This study examines the function of Ang(1-7) in bone micro-architecture and metabolism in an ovariectomized (OVX) rodent model of osteoporosis. OVX rats showed structural and bone metabolic degeneration in parallel with suppressed expressions of the angiotensin converting enzyme-2 (ACE-2)/Ang(1-7)/Mas components. The infusion of Ang(1-7) markedly alleviated the altered bone metabolism and significantly enhanced both trabecular (metaphyseal) and cortical (metaphyseal-diaphyseal) morphometry. Urinary and bones minerals were also improved in OVX rats by Ang(1-7). The infusion of the heptapeptide enhanced ACE-2/Mas receptor expressions, while down-regulated AngII, ACE, and AngII type-1 receptor (AT1R) in OVX animals. Moreover, Ang(1-7) markedly improved osteoprotegerin (OPG) and lowered receptor activator NF-κB ligand (RANKL) expressions. The defensive properties of Ang(1-7) on bone metabolism, structure and minerals were considerably eradicated after blockage of Mas receptor with A-779. Ang(1-7)-induced up-regulated ACE-2/Ang(1-7)/Mas cascade and OPG expressions were abolished and the expressions of ACE/AngII/AT1R and RANKL were provoked by A-779. These findings shows for the first time the novel valuable therapeutic role of Ang(1-7) on bone health and metabolism through the ACE-2/Mas cascade.


Assuntos
Angiotensina I/farmacologia , Osteoporose/prevenção & controle , Ovariectomia/efeitos adversos , Fragmentos de Peptídeos/farmacologia , Peptidil Dipeptidase A/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Enzima de Conversão de Angiotensina 2 , Animais , Western Blotting , Feminino , Humanos , Tamanho do Órgão/efeitos dos fármacos , Osteoporose/etiologia , Osteoporose/metabolismo , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Útero/efeitos dos fármacos , Útero/patologia
8.
Biomed Pharmacother ; 92: 58-68, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28531801

RESUMO

The local role of the renin angiotensin system (RAS) was documented recently beside its conventional systemic functions. Studies showed that the effector angiotensin II (AngII) alters bone health, while inhibition of the angiotensin converting enzyme (ACE-1) preserved these effects. The newly identified Ang1-7 exerts numerous beneficial effects opposing the AngII. Thus, the current study examines the role of Ang1-7 in mediating the osteo-preservative effects of ACEI (captopril) through the G-protein coupled Mas receptor using an ovariectomized (OVX) rat model of osteoporosis. 8 weeks after the surgical procedures, captopril was administered orally (40mgkg-1 d-1), while the specific Mas receptor blocker (A-779) was delivered at infusion rate of 400ngkg-1min-1 for 6 weeks. Bone metabolic markers were measured in serum and urine. Minerals concentrations were quantified in serum, urine and femoral bones by inductive coupled plasma mass spectroscopy (ICP-MS). Trabecular and cortical morphometry was analyzed in the right distal femurs using micro-CT. Finally, the expressions of RAS peptides, enzymes and receptors along with the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) were determined femurs heads. OVX animals markedly showed altered bone metabolism and mineralization along with disturbed bone micro-structure. Captopril significantly restored the metabolic bone bio-markers and corrected Ca2+ and P values in urine and bones of estrogen deficient rats. Moreover, the trabecular and cortical morphometric features were repaired by captopril in OVX groups. Captopril also improved the expressions of ACE-2, Ang1-7, Mas and OPG, while abolished OVX-induced up-regulation of ACE-1, AngII, Ang type 1 receptor (AT1R) and RANKL. Inhibition of Ang1-7 cascade by A-779 significantly eradicated captopril protective effects on bone metabolism, mineralization and micro-structure. A-779 also restored OVX effects on RANKL expression and ACE-1/AngII/AT1R cascade and down-regulated OPG expression and ACE-2/Ang1-7/Mas pathway. In line with the clinical observations of the bone-preservative properties following ACE-1 inhibition, local activation of ACE-2/Ang1-7/Mas signaling and suppressed osteoclastogenesis seem responsible for the osteo-preservative effect of captopril, which could offers a potential therapeutic value in treatment of disabling bone and skeletal muscular diseases.


Assuntos
Angiotensina II/análogos & derivados , Angiotensina I/antagonistas & inibidores , Conservadores da Densidade Óssea/antagonistas & inibidores , Osso e Ossos/efeitos dos fármacos , Captopril/antagonistas & inibidores , Osteoporose Pós-Menopausa/tratamento farmacológico , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/toxicidade , Transdução de Sinais/efeitos dos fármacos , Administração Oral , Angiotensina I/metabolismo , Angiotensina II/administração & dosagem , Angiotensina II/toxicidade , Enzima de Conversão de Angiotensina 2 , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Biomarcadores/sangue , Biomarcadores/urina , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/química , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Captopril/administração & dosagem , Captopril/uso terapêutico , Preparações de Ação Retardada , Feminino , Fêmur , Humanos , Osteólise/induzido quimicamente , Osteólise/prevenção & controle , Osteoporose Pós-Menopausa/induzido quimicamente , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/metabolismo , Ovariectomia , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Ratos Wistar , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismo , Espectrofotometria Atômica , Microtomografia por Raio-X
9.
Cancer Chemother Pharmacol ; 80(1): 55-64, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28502039

RESUMO

PURPOSE: The present study examined the possible involvement of the lipoxygenase (LOX) pathway in cisplatin (CPT)-induced nephrotoxicity. METHODS: Wistar albino rats were challenged with CPT IP injection (7.5 mg/kg) and were sacrificed after one week. Signs of renal dysfunction, including urea and creatinine clearance levels and renal histological structure, were investigated. Gene and protein expression levels of different LOX pathway enzymes and products, including 5-LOX, 12-LOX, 15-LOX, 5-LOX activating protein (FLAP), leukotriene A4 hydrolase (LTA4 hydrolase), leukotriene C4 synthase (LTC4 synthase), LTB4 receptor, and cysteinyl (cys) LT receptor types 1 and 2, were also determined in the kidneys using real-time PCR and western blotting, respectively. The serum and kidney levels of LTB4 and inflammatory markers were also estimated. RESULTS: CPT renal toxicity was established as the creatinine and urea clearance levels were significantly reduced, while the serum levels of creatinine and urea were markedly increased. We reported a considerable up-regulation in the mRNA and protein expression levels of 5-LOX, FLAP, 12-LOX, LTA4 hydrolase, LTC4 synthase, LTB4 receptor, and Cys LT receptor types 1 and 2, while 15-LOX expression did not significantly change in the CPT group. Additionally, LTB4 and inflammatory indicators in serum and renal levels were elevated significantly in the CPT group. Histopathological examination clearly showed the nephrotoxic changes in the renal tissues of CPT-challenged animals. CONCLUSIONS: Our findings suggested, for the first time, the participation of LOX enzymes and products in the signaling pathway leading to CPT-associated nephrotoxicity, which could be the foundation stone for combining LOX pathway attenuators with CPT therapy to decrease CPT-associated renal toxicity.


Assuntos
Cisplatino/toxicidade , Nefropatias/induzido quimicamente , Leucotrienos/metabolismo , Lipoxigenase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Western Blotting , Creatinina/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Nefropatias/fisiopatologia , Testes de Função Renal , Leucotrieno B4/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real
10.
Eur J Pharmacol ; 807: 44-55, 2017 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-28442323

RESUMO

The renin angiotensin system (RAS) regulates numerous systemic functions and is expressed locally in skeletal tissues. Angiotensin1-7 (Ang1-7) is a beneficial member of the RAS, and the therapeutic effects of a large number of angiotensin receptors blockers (ARBs) are mediated by an Ang1-7-dependent cascade. This study examines whether the reported osteo-preservative effects of losartan are mediated through the angiotensin converting enzyme2 (ACE-2)/Ang1-7/Mas pathway in ovariectomized (OVX) rats. Sham and OVX animals received losartan (10mg/kg/d p.o.) for 6 weeks. A specific Mas receptor blocker (A-779) was delivered via mini-osmotic pumps during the losartan treatment period. Serum and urine bone metabolism biomarker levels were measured. Bone trabecular and cortical morphometry were quantified in distal femurs, whereas mineral contents were estimated in ashed bones, serum and urine. Finally, the expression of RAS components, the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) was determined. Losartan significantly improved the elevated bone metabolism marker levels and altered trabecular and cortical structures in OVX animals, and restored normal urinary and skeletal mineral levels. Mas receptor inhibition significantly abolished all osteo-protective effects of losartan and enhanced the deleterious effects of OVX. Losartan enhanced OVX-induced up-regulation of ACE-1, AngII, angiotensin type 1 (AT1) receptor and RANKL expression, and increased ACE-2, Ang1-7, Mas and OPG expression in OVX animals. However, A-779 significantly eradicated the effects of losartan on RAS components and RANKL/OPG expression. Thus, Ang1-7 are involved in the osteo-preservative effects of losartan via Mas receptor, which may add therapeutic value to this well-known antihypertensive agent.


Assuntos
Angiotensina II/análogos & derivados , Angiotensina I/metabolismo , Fêmur/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Angiotensina II/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Enzima de Conversão de Angiotensina 2 , Animais , Feminino , Fêmur/citologia , Fêmur/metabolismo , Fêmur/fisiologia , Losartan/farmacologia , Minerais/sangue , Minerais/urina , Ratos , Ratos Wistar
11.
Biomed Pharmacother ; 87: 575-582, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28081469

RESUMO

In the current investigation, the potential alleviating effects of tianeptine against bone loss induced in ovariectomized (OVX) rats was determined. Two weeks following a bilateral ovariectomy operation, tianeptine treatment (12.5 and 25mg/kg/twice/d) was initiated and continued for twenty-eight consecutive days. Changes in serum and urinary bone turnover biomarkers and osteoclastogenesis-inducing factors were estimated. The femoral bone mineral content was estimated using inductively-coupled-plasma mass spectrometry. Morphometric alterations of distal femoral bones were observed in the cortical and trabecular structures using micro-CT. Finally, femur bones were assessed for histopathological changes. The lack of estrogen significantly increased the levels of bone turnover biomarkers and inflammatory mediators. Mineral concentrations in the femoral bones were reduced in the OVX group. Furthermore, the femoral bone micro-architecture determined using micro-CT and histopathology were significantly altered by estrogen deficiency. Tianeptine, particularly the higher dose, corrected the elevated levels of bone metabolic products and pro-inflammatory cytokines. Tianeptine also improved mineral concentrations in femoral bones and the disturbed morphometric and histopathological features in OVX rats. In conclusion, tianeptine alleviated the osteoporotic changes in OVX animals, which may be via inhibition of the hypothalamic-pituitary-adrenal axis stress and osteoclastogenesis-provoking factors, suggesting attenuation of bone matrix degradation and osteoclast stimulation.


Assuntos
Antidepressivos/farmacologia , Osteoporose/tratamento farmacológico , Tiazepinas/farmacologia , Animais , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Citocinas/metabolismo , Estrogênios/metabolismo , Feminino , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Inflamação/metabolismo , Osteoporose/metabolismo , Ovariectomia/métodos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Ratos , Ratos Wistar
12.
Oxid Med Cell Longev ; 2016: 5436745, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27239252

RESUMO

Background and Objective. High-cholesterol diet (HCD) intends to increase the oxidative stress in liver tissues inducing hepatotoxicity. Rutin is a natural flavonoid (vitamin p) which is known to have antioxidative properties. The aim of the present study was to investigate the potential effects of Rutin on hypercholesterolemia-induced hepatotoxicity in rats. Materials and Methods. Male Wistar rats were divided into four groups: G-I control, G-II Rutin, G-III HCD, and G-IV Rutin + HCD. The liver functions and lipid profile were used to evaluate the HCD-induced hepatotoxicity. Quantitative real time-PCR was carried out to evaluate the expression levels of genes in TGF-ß/Smad signaling pathway. Results. Rutin in combination with HCD showed a significant protective effect against hepatotoxicity. HCD caused significant increase in the mRNA expression of transforming growth factor beta (TGF-ß), Mothers Against Decapentaplegic Homolog 2 (Smad-2), Mothers Against Decapentaplegic Homolog 4 (Smad-4), Bcl-2-binding component 3 (Bbc3), caspase-3, P53 and Interleukin-6 (IL-6) and decrease in the expression levels of Cyclin depended kinase inhibitor (P21) and Interleukin-3 (IL-3) in hepatic cells. Conclusion. TGF-ß/Smad signaling pathway is involved in HCD-induced hepatotoxicity and Rutin inhibits the hepatotoxicity via suppressing this pathway. Therefore, Rutin might be considered as a protective agent for hepatotoxicity.


Assuntos
Colesterol/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Hepatopatias/tratamento farmacológico , Rutina/uso terapêutico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Peso Corporal/efeitos dos fármacos , Caspase 3/metabolismo , Interleucinas/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hepatopatias/sangue , Hepatopatias/enzimologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos Wistar , Rutina/farmacologia , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo
13.
BMC Complement Altern Med ; 15: 204, 2015 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-26122042

RESUMO

BACKGROUND: Diabetes mellitus with the successive generation of reactive oxygen species signifies a major risk factor for testicular dysfunction. Antioxidant supplements are one of the best options to prevent such disorder. In the present study, lutein as dietary supplement has been used to explore its potential protective effects against diabetes-induced oxidative stress in testicular cells. METHODS: Diabetes was induced using a single i.p. injection of streptozotocin (STZ). Lutein was mixed with rat chow powder and supplemented to diabetic rats for 5 weeks. Serum testosterone levels were estimated. In testicular cells, thiobarbituric acid reactive substances (TBARS), total sulfhydryl groups (T-GSH), non-protein sulfhydryl groups (NP-SH), superoxide dismutase (SOD) and catalase (CAT) activities were measured. Pro-inflammatory mediators like tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) were measured in the testis. Nucleic acids and total protein (TP) levels were also estimated in testicular cells. Histopathological changes were evaluated in testis. RESULTS: Serum testosterone level was significantly decreased in diabetic animals compared to controls. Diabetes markedly reduced T-GSH, NP-SH, CAT and SOD, while TBARS, TNF-α and IL-1ß levels were increased in the diabetic testis compared to non-diabetic controls. Lutein supplementation, significantly and dose dependently increased the serum testosterone level. The elevated TBARS levels were significantly decreased compared to diabetic group, while the decreased levels of T-GSH and NP-SH and activities of CAT and SOD were found increased by lutein treatments in dose dependent manner. Lutein pretreatment also inhibited the TNF-α and IL-1ß levels compared to diabetic group. The decreased values of nucleic acids and total protein in diabetic group were also significantly increased in lutein supplemented groups. The histopathological evaluation revealed protection the damaged testicular cells in the diabetic rats by lutein supplementation. CONCLUSION: These findings showed that lutein has potential beneficial effects in diabetes-induced testicular damage, probably through its antioxidant and anti-inflammatory properties.


Assuntos
Suplementos Nutricionais , Luteína/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Luteína/administração & dosagem , Masculino , Ratos , Estreptozocina/efeitos adversos
14.
Neurol Res ; 37(10): 924-33, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26187552

RESUMO

OBJECTIVES: Present study aims to investigate the ameliorative effects of naringenin (NG) on experimentally induced diabetic neuropathy (DN) in rats. METHODS: Diabetes was induced by single intraperitoneal injection of streptozotocin (STZ, 60  g/kg). Naringenin (25 and 50 mg/kg/day) treatment was started 2 weeks after the diabetes induction and continued for five consecutive weeks. Pain threshold behaviour tests were performed at the end of the treatment. Serum levels of glucose, insulin and pro-inflammatory cytokines were assessed. In sciatic tissues, markers oxidative stress, cytokines and neurotrophic factors were measured. RESULTS: NG treatments showed significant decrease in paw-withdrawal (P < 0.01) and tail-flick latency (P < 0.01). The drug attenuated the diabetic-induced changes in serum glucose, insulin and pro-inflammatory cytokines including tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6). In sciatic nerve, the diabetic-induced alterations in interleukins and oxidative stress biomarkers were significantly attenuated by NG. Decreased sciatic expressions of insulin growth factor (IGF) and nerve growth factor (NGF) in diabetic rats were also ameliorated by NG. Diabetes-induced dysregulated levels of nitric oxide (NO), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were ameliorated by NG. Histological analysis showed that NG corrected the altered sciatic changes in diabetic animals. DISCUSSION: We suggest that neuro-protective effect of NG molecules in sciatic nerve of diabetic rats, through its anti-diabetic as well as antioxidant and anti-inflammatory properties.


Assuntos
Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/prevenção & controle , Flavanonas/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Animais , Glicemia , Citocinas/sangue , Neuropatias Diabéticas/induzido quimicamente , Modelos Animais de Doenças , Insulina/sangue , Masculino , Fator de Crescimento Neural/metabolismo , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia , Estreptozocina
15.
Drug Dev Res ; 76(4): 204-14, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26109469

RESUMO

Preclinical Research This study evaluated the effects of the carvedilol, a nonselective ß-adrenoceptor anatgonist with α1-adrenoceptor antagonist activity, in a rat model of experimentally induced ulcerative colitis (UC). UC was produced using acetic acid (AA) in animals previously treated with carvedilol (30 mg/kg po, qd) for seven days. Mucus content, lipid peroxidation (LPO) products, sulfhydryl groups, antioxidant enzyme activities, proinflammatory cytokines, prostaglandin E2 and nitric oxide levels were measured in colonic tissues and histopathological changes were assessed. LPO and proinflammatory biomarkers were markedly increased, while mucus content, sulfhydryl groups and enzymatic activities were inhibited in animals administered AA. Pretreatment with carvedilol attenuated LPO elevation, mucus content and sulfhydryl group inhibitions. Antioxidant enzymatic activity and proinflammatory biomarker levels were also restored in carvedilol-pretreated animals. Colonic protection associated with carvedilol pretreatment was further confirmed by histopathological assessment and found to be similar to the standard therapy of mesalazine (100 mg/kg po qd), suggesting that the effects of carvedilol action may be attributable to its anti-inflammatory and antioxidant properties.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Carbazóis/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Propanolaminas/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Carbazóis/farmacologia , Carvedilol , Colite Ulcerativa/metabolismo , Colo/metabolismo , Citocinas/metabolismo , DNA/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Masculino , Malondialdeído/metabolismo , Muco/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Propanolaminas/farmacologia , RNA/metabolismo , Ratos Wistar , Compostos de Sulfidrila/metabolismo
16.
J Mol Neurosci ; 56(2): 440-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25929832

RESUMO

Diabetic retinopathy is widely recognized as a neurodegenerative disease of the eye. Increased oxidative stress has been considered the central factor in damaging neural retina in diabetes. Flavonoids, being powerful antioxidants, play protective roles in several oxidative stress-mediated neurodegenerative diseases. In this study, we analyzed the neuroprotective effects of a potential flavonoid, rutin, in the diabetic rat retina. Diabetes was induced in male Wistar rats by single injection of streptozotocin (65 mg/kg). In age-matched control (non-diabetic) and 1 week of diabetic rats, rutin (100 mg/kg/day) was orally administered and continued for 5 weeks. In another group of diabetic rats, only saline was supplemented. After treatments, retinas from all the groups were isolated and analyzed for potential neurotrophic factors and apoptotic and oxidative stress markers using biochemical and immunoblotting techniques. Our results indicate that rutin possesses antidiabetic activity, as blood glucose level decreased and insulin level increased in diabetic rats. In the diabetic retina, rutin supplementation enhanced the reduced levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glutathione (GSH) (P < 0.05), and reduced the level of thiobarbituric acid-reactive substances (TBARS) (P < 0.05). In addition, rutin treatment showed antiapoptotic activity by decreasing the level of caspase-3 and increasing the level of Bcl-2 in the diabetic retina. These results suggest the effectiveness of rutin in ameliorating the levels of neuroprotective factors in diabetic retina. Therefore, rutin might be a potential flavonoid that can prevent the retinal damage and subsequently the development of diabetic retinopathy.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Rutina/uso terapêutico , Animais , Apoptose , Glicemia/metabolismo , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Fatores de Crescimento Neural/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Retina/efeitos dos fármacos , Retina/metabolismo , Rutina/farmacologia
17.
Neurosciences (Riyadh) ; 20(2): 115-23, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25864063

RESUMO

OBJECTIVE: To evaluate the potential therapeutic value of telmisartan (TMT) against diabetic neuropathy (DN) and associated pain in Wistar rats. METHODS: Peripheral DN was induced by a single intraperitoneal streptozotocin injection (55 mg/kg), and 3 weeks later TMT treatment was started (5 and 10 mg/kg/day), and continued for 4 weeks. Mechanical nociceptive threshold, motor coordination, and thermal nociceptive threshold tests were performed before and after TMT treatment. In serum, glucose, pro-inflammatory cytokines including tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 were assessed. Nerve growth factor (NGF) levels and histopathological changes were estimated in the sciatic nerve. This study was conducted at the Experimental Animal Care Center, Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia between January 2013 and May 2014. RESULTS: We observed a significant reduction in mechanical nociceptive threshold, motor coordination, and thermal nociceptive threshold in diabetic animals. The TMT treatment significantly enhanced the reduced mechanical nociceptive threshold. The untreated diabetic animals revealed a significant decrease in sciatic NGF, which was markedly attenuated by TMT. The elevated serum levels of cytokines in diabetic animals were inhibited by the TMT treatments. Histopathological evaluation showed obvious nerve degeneration in the diabetic group that was eliminated in the TMT treated diabetic groups. CONCLUSION: Telmisartan has a potential neuro-protective effect on peripheral DN; this is mediated through its anti-inflammatory effects and its dual properties as an angiotensin receptor blocker, and a partial peroxisome proliferator activator receptor-gamma ligand.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Benzimidazóis/uso terapêutico , Benzoatos/uso terapêutico , Neuropatias Diabéticas/complicações , Neuropatias Diabéticas/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Animais , Citocinas/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Neuropatias Diabéticas/patologia , Hiperalgesia/patologia , Inflamação/patologia , Masculino , Atividade Motora/efeitos dos fármacos , Medição da Dor/efeitos dos fármacos , Estimulação Física , Ratos , Ratos Wistar , Nervo Isquiático/patologia , Telmisartan
18.
Acta Pharmacol Sin ; 36(2): 209-20, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25544359

RESUMO

AIM: Depression is a risk factor for impaired bone mass and micro-architecture, but several antidepressants were found to increase the incidence of osteoporotic fractures. In the present study we used ovariectomized (OVX) rats as a model of osteoporosis to investigate the effects of the antidepressant bupropion on the femoral bones. METHODS: OVX animals were treated with bupropion (30, 60 mg·kg(-1)·d(-1)) for six weeks. Bone turnover biomarkers (urinary DPD/Cr ratio, serum BALP, OC, TRAcP 5b, CTX and sRANKL levels) and inflammatory cytokines (TNF-α, IL-1ß and IL-6) were determined using ELISA. Inductively coupled plasma mass spectroscopy (ICP-MS) was used to determine the femoral bone mineral concentrations. The cortical and trabecular morphometric parameters of femoral bones were determined using micro-CT scan and histopathology. RESULTS: In OVX rats, the levels of bone turnover biomarkers and inflammatory cytokines were significantly elevated and femoral bone Ca(2+) and PO4(3-) concentrations were significantly reduced. Moreover, cortical and trabecular morphometric parameters and histopathology of femoral bones were severely altered by ovariectomy. Bupropion dose-dependently inhibited the increases in bone turnover biomarkers and inflammatory cytokines. OVX rats treated with the high dose of bupropion showed normal mineral concentrations in femoral bones. The altered morphometric parameters and histopathology of femoral bones were markedly attenuated by the treatment. CONCLUSION: Bupropion exerts osteo-protective action in OVX rats through suppressing osteoclastogenesis-inducing factors and inflammation, which stabilize the osteoclasts and decrease bone matrix degradation or resorption.


Assuntos
Antidepressivos/efeitos adversos , Bupropiona/efeitos adversos , Osteoporose/fisiopatologia , Animais , Densidade Óssea/efeitos dos fármacos , Feminino , Fêmur/efeitos dos fármacos , Ovariectomia/métodos , Ratos , Ratos Wistar
19.
BMC Complement Altern Med ; 14: 49, 2014 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-24507431

RESUMO

BACKGROUND: Overproduction of free radicals and decreased antioxidant capacity are well-known risk factors for inflammatory bowel diseases. Gymnema sylvestre (GS) leaves extract is distinguished for its anti-diabetic, antioxidant and anti-inflammatory properties. Present study is designed to evaluate the preventative activities of GS against acetic acid (AA)-induced ulcerative colitis in Wistar rats. METHODS: Experimentally ulcerative colitis (UC) was induced by AA in animals pretreated with three different doses of GS leaves extract (50, 100, 200 mg/kg/day) and a single dose of mesalazine (MES, 300 mg/kg/day) for seven days. Twenty four hours later, animals were sacrificed and the colonic tissues were collected. Colonic mucus content was determined using Alcian blue dye binding technique. Levels of thiobarbituric acid reactive substances (TBARS), total glutathione sulfhydryl group (T-GSH) and non-protein sulfhydryl group (NPSH) as well as the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were estimated in colon tissues. Colonic nucleic acids (DNA and RNA) and total protein (TP) concentrations were also determined. Levels of pro-inflammatory cytokines including interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) as well as prostaglandin E2 (PGE2) and nitric oxide (NO) were estimated in colonic tissues. The histopathological changes of the colonic tissues were also observed. RESULTS: In AA administered group TBARS levels were increased, while colonic mucus content, T-GSH and NP-SH, SOD and CAT were reduced in colon. Pretreatment with GS inhibited TBARS elevation as well as mucus content, T-GSH and NP-SH reduction. Enzymatic activities of SOD and CAT were brought back to their normal levels in GS pretreated group. A significant reduction in DNA, RNA and TP levels was seen following AA administration and this inhibition was significantly eliminated by GS treatment. GS pretreatment also inhibited AA-induced elevation of pro-inflammatory cytokines, PGE2 and NO levels in colon. The apparent UC protection was further confirmed by the histopathological screening. CONCLUSION: The GS leaves extract showed significant amelioration of experimentally induced colitis, which may be attributed to its anti-inflammatory and antioxidant property.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Colite Ulcerativa/prevenção & controle , Colo/efeitos dos fármacos , Gymnema sylvestre , Fitoterapia , Extratos Vegetais/uso terapêutico , Ácido Acético , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Catalase/metabolismo , Colite/induzido quimicamente , Colite/metabolismo , Colite/prevenção & controle , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colo/metabolismo , Glutationa/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Extratos Vegetais/farmacologia , Folhas de Planta , Ratos Wistar , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico , Fator de Necrose Tumoral alfa/metabolismo
20.
Neurol Sci ; 35(7): 1003-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24413816

RESUMO

Diabetes-induced damages in brain are known as diabetic encephalopathy, which is well characterized by cellular, molecular and functional changes in the brain of diabetic subjects and rodents. However, little is known about the mechanism of damages and the therapeutic strategies in ameliorating those damages in the diabetic brain. In this study, we utilized a flavonoid, morin which is emerging as a potent drug against a wide range of free radical-mediated as well as neurodegenerative diseases. Morin (15 and 30 mg/kg body weight/day) was orally administered to two different groups of rats after 1 week of diabetes induction, and continued for five consecutive weeks. Two other untreated groups of diabetic and non-diabetic rats were used to compare with drug-treated groups. After drug treatments, cerebral cortex of the brain harvested and analyzed for different factors. Morin supplementation especially at high dose increased the levels of insulin, reduced glutathione, superoxide dismutase and catalase activities, and decreased fasting glucose and thiobarbituric acid reactive substances in the diabetic brain compared to untreated diabetic rats (P < 0.05). Morin also significantly decreased the level of inflammatory markers (TNFα, IL1ß, IL-6) in the diabetic brain compared to untreated diabetic rats. Furthermore, the drug influenced an increase in the level of neurotrophic factors (BDNF, NGF and IGF-1) in the diabetic brain compared to untreated diabetic rats (P < 0.05). Thus, our results indicate a beneficial effect of morin by decreasing oxidative stress, inflammation and increasing the neurotrophic support in the diabetic brain, which may ameliorate diabetic encephalopathy.


Assuntos
Antioxidantes/uso terapêutico , Diabetes Mellitus Experimental , Flavonoides/uso terapêutico , Inflamação , Fatores de Crescimento Neural/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Catalase/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Flavonoides/farmacologia , Glutationa/metabolismo , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
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