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1.
Antioxidants (Basel) ; 9(8)2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32764528

RESUMO

Diabetic retinopathy (DR) is an important microvascular complication of diabetes and one of the leading causes of blindness in developed countries. Two large clinical studies showed that fenofibrate, a peroxisome proliferator-activated receptor type α (PPAR-α) agonist, reduces DR progression. We evaluated the protective effects of fenofibrate on retinal/choroidal vascular endothelial cells under oxidative stress and investigated the underlying mechanisms using RF/6A cells as the model system and paraquat (PQ) to induce oxidative stress. Pretreatment with fenofibrate suppressed reactive oxygen species (ROS) production, decreased cellular apoptosis, diminished the changes in the mitochondrial membrane potential, increased the mRNA levels of peroxiredoxin (Prx), thioredoxins (Trxs), B-cell lymphoma 2 (Bcl-2), and Bcl-xl, and reduced the level of B-cell lymphoma 2-associated X protein (Bax) in PQ-stimulated RF/6A cells. Western blot analysis revealed that fenofibrate repressed apoptosis through cytosolic and mitochondrial apoptosis signal-regulated kinase-1 (Ask)-Trx-related signaling pathways, including c-Jun amino-terminal kinase (JNK) phosphorylation, cytochrome c release, caspase 3 activation, and poly (ADP-ribose) polymerase-1 (PARP-1) cleavage. These protective effects of fenofibrate on RF/6A cells may be attributable to its anti-oxidative ability. Our research suggests that fenofibrate could serve as an effective adjunct therapy for ocular oxidative stress-related disorders, such as DR.

2.
J Diabetes Res ; 2014: 540326, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25525608

RESUMO

Adiponectin has been associated with increased risks of microvascular complications in diabetes; however, its role in the development of diabetic retinopathy (DR) is unknown. Fenofibrate is a lipid-lowering agent that has been shown to be capable of preventing DR progression. We investigated the expression of adiponectin and its receptors in DR and evaluated the effects of fenofibrate on their expression. The mRNA and protein levels of adiponectin and its receptors were elevated in retinas of streptozotocin-induced diabetic rats and were suppressed following fenofibrate treatment. Immunofluorescence staining demonstrated that adiponectin and adipoR1 were expressed in cells located within blood vessels, the retinal ganglion, and the inner nuclear layer. AdipoR1 was strongly expressed whereas adipoR2 was only weekly expressed in vascular endothelial cells. The in vitro experiments showed that adiponectin expression was induced by high glucose concentrations in RGC-5 and RAW264.7 cells and was suppressed following fenofibrate treatment. AdipoR1 and adipoR2 levels in RGC-5 cells were elevated in high glucose concentrations and suppressed by fenofibrate. Our results demonstrated that adiponectin may be a proinflammatory mediator in diabetic retinas and fenofibrate appears to modulate the expression of adiponectin and its receptors in diabetic retinas, effectively reducing DR progression.


Assuntos
Adiponectina/metabolismo , Anti-Inflamatórios/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/prevenção & controle , Fenofibrato/farmacologia , Mediadores da Inflamação/metabolismo , Retina/efeitos dos fármacos , Estreptozocina , Adiponectina/sangue , Adiponectina/genética , Animais , Humor Aquoso/metabolismo , Glicemia/metabolismo , Linhagem Celular , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/genética , Retinopatia Diabética/sangue , Retinopatia Diabética/etiologia , Retinopatia Diabética/genética , Feminino , Camundongos , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Receptores de Adiponectina/efeitos dos fármacos , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Retina/metabolismo
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