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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.
Poult Sci ; 100(8): 101103, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34229218

RESUMO

Practical methods for preventing embryotoxicity in chickens that are caused by aflatoxin-B1 (AFB1) are currently rare. Binding absorbers are commonly used in feeding stuff to reduce laying hens' exposure to off-contaminated diets, thus reducing residue exposure to fertilized eggs. Nonetheless, several adsorbents have been shown to affect the use of nutrients and the absorption of minerals in poultry. Thus, seeking an effective strategy to counter or control embryotoxicity in broiler chicks caused by AFB1 is a problem. A total of 180 embryonated eggs were injected with 36 ng AFB1 with or without 5.90 mg L-methionine (Met) 30 embryonated eggs each, followed by incubation in an incubator until hatching time. The in ovo injection of Met significantly reduced toxicity caused by AFB1 in broiler embryos by enhancing the liver and kidney functions, lipid profiles, and alleviated oxidative stress during the incubation period. Furthermore, the relative gene expressions (SSTR5, TSH-ß, Bcl-2, GSH-Px, GST-a, and SOD in the liver) were up-regulated with in ovo injection of AFB1+Met compared to AFB1 alone. Moreover, there was a dowin-regulated trend in Bax, Caspases-3, Caspases-7, Caspases-9, CYP1A1, CYP2H1, and P53 gene expression with in ovo injection of AFB1+Met compared to AFB1 alone. The in ovo injection of Met led to less apoptotic cells in liver tissues. Such results might be necessary for the poultry industry as it is focused on managing the embryotoxicity of AFB1, which affecting poultry production and welfare. Results from this study demonstrated that in ovo Met injection could alleviate AF-induced toxicity in chicken embryos.


Assuntos
Antioxidantes , Galinhas , Aflatoxina B1/toxicidade , Animais , Apoptose , Embrião de Galinha , Feminino , Fígado , Metionina , Óvulo
3.
Int J Med Sci ; 17(18): 3098-3106, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173431

RESUMO

Background and objectives: Although diabetic-induced hepatotoxicity is less common, it can be included in the list of target organ pathologies associated with diabetes. This study aimed to investigate the potential therapeutic role of sacubitril/valsartan (LCZ696) in modulating oxidative and inflammatory injuries and liver fibrosis in STZ-induced hyperglycemic rats in comparison to valsartan alone. Materials and Methods: Following the induction of diabetes using a single dose of streptozotocin (STZ), STZ-induced hyperglycemic animals were administered LCZ696 or valsartan for 6 weeks. Glucose, transaminases, lipid profile, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin - 6 (IL-6), were estimated using the obtained serum. Oxidative stress biomarkers including thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) were measured in the liver homogenate. Additionally, the levels of TNF-α, IL-1ß, IL-6, and nuclear factor - kappa ß (NF-κB) levels were estimated in hepatic tissue. To assess the general histopathological changes, harvested liver tissue was treated with hematoxylin and eosin or Masson's trichrome staining to detect fibrosis. Results: STZ-induced hyperglycemic rats demonstrated high blood glucose, dyslipidemia, and significant elevation in hepatic transaminases, proinflammatory cytokines, NF-κB, lipid peroxidation, and hepatic fibrosis, with impairment in antioxidant enzymes. In STZ-induced hyperglycemic rats, the administration of LCZ696 ameliorated hyperglycemia, dyslipidemia, improved liver functions, and boosted antioxidants enzymes. Furthermore, LCZ696 therapy attenuated oxidation, inflammation, progression of liver injury, and hepatic fibrosis. LCZ696 was superior to valsartan in reducing AST, hepatic fibrosis, tissue IL-1ß, TNF-α and NF-κB. In addition, compared with the valsartan group, LCZ696 significantly increased the antioxidant parameters such as GSH, SOD, CAT and GPx. Conclusion: Collectively, our data demonstrated that LCZ696 could suppress the progression of diabetes-induced hepatic fibrosis, correlating with reduced oxidative stress, hepatic inflammation and NF-κB compared with valsartan alone.

4.
Nat Prod Res ; : 1-9, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32945198

RESUMO

Four undescribed cembranoids, sarcoroseolides A-D (1-4) along with nine reported related cembranoids (5-13) were isolated from the soft coral Sarcophyton roseum. The chemical structures of sarcoroseolides A-D were elucidated by extensive 1 D and 2 D NMR as well as HR-ESIMS spectroscopic data. Moreover, the geometric and absolute configurations were assigned by the modified Mosher's method and/or NOESY experiments. The extract and the isolated metabolites were evaluated for their potential anti-inflammatory and cytotoxic activities.

5.
PeerJ ; 8: e9196, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32596035

RESUMO

Background: Diabetic nephropathy (DN) is among the most common microvascular complications of diabetes resulting in end-stage renal disease and therefore search for candidates which can ameliorate the kidney function is needed simultaneously with standard diabetic pharmacotherapy. The current study was aimed to investigate the effect of long term sacubitril/valsartan therapy (LCZ696) in diabetic rats to assess its ameliorative impact against various pathological parameters such as oxidative stress, inflammation and glomerulosclerosis associated with chronic DN. Methods: A single dose (60 mg/kg/day) of STZ was used to induce type 1 diabetes in adult male wistar rats. 2 weeks after diabetes induction, these rats were treated orally with valsartan (31 mg/kg) or LCZ696 (68 mg/kg) for 6 weeks. At end of the treatment period, serum and kidney samples were collected and analyzed. The serum levels of glucose, insulin, urea, creatinine, TNF-α, IL-1ß, IL-6 and IL-10 levels were estimated. In renal tissue homogenate, the levels of inflammatory markers such as TNF-α, IL-1ß, IL-6, NF-kB along with oxidative stress biomarkers including thiobarbituric acid-reacting substances (TBARs), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) were assessed. Histological changes were observed in kidney. Results: Time course therapy withLCZ696 and valsartan in diabetic rats resulted in significant reduction of serum glucose, urea and creatinine levels (P < 0.05). Additionally, serum of treated diabetic rats showed a diminution in inflammatory (TNF-α, IL-1ß, IL-6) and increment in anti-inflammatory (IL-10) cytokines levels (P < 0.05). Tissue homogenate of the kidney extracted from LCZ696 and valsartan treated diabetic rats revealed a substantial reduction in the levels of inflammatory markers such as TNF-α, IL-1ß, IL-6, NF-kB and sufficient restoration of anti-oxidant enzyme levels (P < 0.05). Finally, in the histological sections of the kidney, prevention of renal injury was observed with limited necrosis and inflammatory cells infiltration. Conclusion: Present data suggest that LCZ696 has sufficient therapeutic potential to restrict DN progression through inhibiting inflammation, oxidative stress and glomerulosclerosis.

6.
Nat Prod Res ; : 1-7, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32498569

RESUMO

Glycyrrhiza inflata Batalin is among the three glycyrrhizin producing Glycyrrhiza species and can be distinguished from other species with regard to its retrochalcone contents. Seven retrochalcones, echinatin and licochalcones A, C, D, E, K, and L were isolated and characterized from the chloroform extract of G. inflata roots. Among the isolates, licochalcone L was found to be previously undescribed. Structure elucidation of these specialised metabolites was achieved through NMR and mass spectroscopic data analyses.

7.
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
8.
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
9.
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
10.
Nutrients ; 9(10)2017 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-29064407

RESUMO

Diabetic retinopathy (DR) is one of the leading causes of decreased vision and blindness worldwide. Diabetes-induced oxidative stress is believed to be the key factor that initiates neuronal damage in the diabetic retina leading to DR. Experimental approaches to utilize dietary flavonoids, which possess both antidiabetic and antioxidant activities, might protect the retinal damage in diabetes. The aim of this study was to investigate the potential protective effects of naringenin in the retina of streptozotocin-induced diabetic rats. Diabetic rats were orally treated and untreated with naringenin (50 mg/kg/day) for five weeks and retinas were analyzed for markers of oxidative stress, apoptosis and neurotrophic factors. Systemic effects of naringenin treatments were also analyzed and compared with untreated groups. The results showed that elevated levels of thiobarbituric acid reactive substances (TBARs) and decreased level of glutathione (GSH) in diabetic rats were ameliorated with naringenin treatments. Moreover, decreased levels of neuroprotective factors (Brain derived neurotrophic factor (BDNF)), tropomyosin related kinase B (TrkB) and synaptophysin in diabetic retina were augmented with naringenin treatments. In addition, naringenin treatment ameliorated the levels of apoptosis regulatory proteins; B cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax) and caspase-3 in the diabetic retina. Thus, the study demonstrates the beneficial effects of naringenin that possesses anti-diabetic, antioxidant and antiapoptotic properties, which may limit neurodegeneration by providing neurotrophic support to prevent retinal damage in diabetic retinopathy.


Assuntos
Apoptose/efeitos dos fármacos , Flavanonas/farmacologia , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Retina/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Glicemia/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Modelos Animais de Doenças , Glutationa/metabolismo , Hipoglicemiantes/farmacologia , Masculino , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Ratos , Ratos Wistar , Retina/metabolismo , Sinaptofisina/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
11.
J Hand Surg Am ; 42(11): 934.e1-934.e10, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28951098

RESUMO

Mangled upper extremity, as a result of trauma, is a life-altering event requiring a multidisciplinary approach for a successful outcome. All attempts are made to salvage the extremity and preserve function, which may require multiple complex procedures. This paper discusses the importance of a systematic reconstructive sequence and provides a review of commonly utilized techniques, supported with illustrative cases.


Assuntos
Traumatismos do Braço/diagnóstico , Traumatismos do Braço/cirurgia , Salvamento de Membro , Equipe de Assistência ao Paciente/organização & administração , Procedimentos Cirúrgicos Reconstrutivos/métodos , Algoritmos , Terapia Combinada/métodos , Feminino , Seguimentos , Fraturas Ósseas/cirurgia , Humanos , Escala de Gravidade do Ferimento , Masculino , Traumatismos dos Nervos Periféricos/cirurgia , Lesões dos Tecidos Moles/cirurgia , Resultado do Tratamento , Extremidade Superior/lesões , Extremidade Superior/cirurgia
12.
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
13.
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
14.
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
15.
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
16.
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
18.
J Orthop Surg Res ; 11: 46, 2016 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-27106260

RESUMO

BACKGROUND: Limited-incision total hip arthroplasty (THA) preserves hip abductors, posterior capsule, and external rotators potentially diminishing dislocation risk. However, potential complications also exist, such as component malposition. Specific implants have been manufactured that enhance compatibility with this technique, while preserving metaphyseal bone; however, little data exists documenting early complications and component position. The purpose was to evaluate primary THA using a curved, bone-sparing stem inserted through the anterior approach with respect to component alignment and early complications. METHODS: In a retrospective analysis of 108 cases, the surgical technique was outlined and the occurrence of intraoperative fractures, postoperative dislocations, infection, and limb length inequality was determined. Femoral stem and acetabular cup alignment was quantified using the initial postoperative radiographs. Patient follow-up averaged 12.9 (range 2 to 36) months. RESULTS: There were eight (7.4 %) complications requiring revision surgery in three (2.8 %) patients with three (2.8 %) infections and three (2.8 %) dislocations. Intraoperative complications included one calcar fracture above the lesser trochanter. Leg length inequality >5 mm was present in three (2.8 %) patients. Radiographic analysis showed that femoral neutral alignment was achieved in 95 hips (88.0 %). All femoral stems demonstrated satisfactory fit and fill and no evidence of subsidence, osteolysis, or loosening. An average abduction angle of 44.8° (± 5.3) and average cup anteversion of 16.2° (± 4.2) were also noted. CONCLUSIONS: Although the technique with this implant and approach is promising, it does not appear to offer important advantages over standard techniques. However, the findings merit further, long-term study.


Assuntos
Artroplastia de Quadril/métodos , Prótese de Quadril , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/instrumentação , Feminino , Seguimentos , Articulação do Quadril/diagnóstico por imagem , Humanos , Desigualdade de Membros Inferiores/etiologia , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Falha de Prótese , Infecções Relacionadas à Prótese/cirurgia , Radiografia , Reoperação , Estudos Retrospectivos
19.
Toxicol Mech Methods ; 25(5): 417-23, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26360969

RESUMO

Riboflavin (vitamin B2) is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is therefore required by all flavoproteins. Riboflavin also works as an antioxidant by scavenging free radicals. The present study was designed to evaluate the effects of riboflavin against acute lungs injury induced by the administration of a single intranasal dose (20 µg/rat) of lipopolysaccharides (LPS) in experimental rats. Administration of LPS resulted in marked increase in malondialdehyde (MDA) level (p < 0.01) and MPO activity (p < 0.001), whereas marked decrease in glutathione (GSH) content (p < 0.001), glutathione reductase (GR) (p < 0.001) and glutathione peroxidase (p < 0.01) activity. These changes were significantly (p < 0.001) improved by treatment with riboflavin in a dose-dependent manner (30 and 100 mg/kg, respectively). Riboflavin (100 mg/kg, p.o.) showed similar protective effects as dexamethasone (1 mg/kg, p.o.). Administration of LPS showed marked cellular changes including interstitial edema, hemorrhage, infiltration of PMNs, etc., which were reversed by riboflavin administration. Histopathological examinations showed normal morphological structures of lungs tissue in the control group. These biochemical and histopathological examination were appended with iNOS and CAT gene expression. The iNOS mRNA expression was increased significantly (p < 0.001) and levels of CAT mRNA expression was decreased significantly (p < 0.001) in the animals exposed to LPS, while treatment with riboflavin significantly (p < 0.01) improved expression of both gene. In conclusion, the present study clearly demonstrated that riboflavin caused a protective effect against LPS-induced ALI. These results suggest that riboflavin may be used to protect against toxic effect of LPS in lungs.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Antioxidantes/uso terapêutico , Lipopolissacarídeos/toxicidade , Riboflavina/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Antioxidantes/administração & dosagem , Catalase/genética , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Óxido Nítrico Sintase Tipo II/genética , Ratos Wistar , Riboflavina/administração & dosagem
20.
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
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