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1.
Histochem Cell Biol ; 161(3): 239-253, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37943325

RESUMO

Diabetes mellitus is a chronic metabolic disease characterized by persistent hyperglycemia, revealing a decrease in insulin efficiency. The sustained glucotoxic pancreatic microenvironment increases reactive oxygen species generation, resulting in chronic oxidative stress responsible for massive DNA damage. This triggers PARP-1 activation with both NAD+ and ATP depletion, affecting drastically pancreatic beta cells' energy storage and leading to their dysfunction and death. The aim of the present study is to highlight the main histological changes observed in pancreatic islets pre-treated with a unique NADH intraperitoneal injection in a streptozotocin-(STZ)-induced diabetes model. In order to adjust NADH doses, a preliminary study with three different doses, 500 mg/kg, 300 mg/kg, and 150 mg/kg, respectively, was conducted. Subsequently, and on the basis of the results of the aforementioned study, Wistar rats were randomly divided into four groups: non-diabetic control group, diabetics (STZ 45 mg/kg), NADH-treated group (150 mg/kg) 15 min before STZ administration, and NADH-treated group (150 mg/kg) 15 min after STZ administration. The effect of NADH was assessed by blood glucose level, TUNEL staining, histo-morphological analysis, and immunohistochemistry. The optimum protective dose of NADH was 150 mg/kg. NADH effectively decreased hyperglycemia and reduced diabetes induced by STZ. Histologically, NADH pre-treatment revealed a decrease in beta cell death favoring apoptosis over necrosis and therefore preventing inflammation with further beta cell destruction. Our data clearly demonstrate that NADH prior or post-treatment could effectively prevent the deleterious loss of beta cell mass in STZ-induced diabetes in rats and preserve the normal pancreatic islet's function.


Assuntos
Diabetes Mellitus Experimental , Hiperglicemia , Células Secretoras de Insulina , Ratos , Animais , NAD/efeitos adversos , Ratos Wistar , Estreptozocina/efeitos adversos , Injeções Intraperitoneais , Insulina/metabolismo , Hiperglicemia/tratamento farmacológico , Hiperglicemia/induzido quimicamente , Hiperglicemia/prevenção & controle , Diabetes Mellitus Experimental/metabolismo , Glicemia/metabolismo
2.
Cells ; 13(10)2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38786103

RESUMO

Cigarette smoke is one of the main factors in Chronic Obstructive Pulmonary Disease (COPD), a respiratory syndrome marked by persistent respiratory symptoms and increasing airway obstruction. Perturbed NAD+/NADH levels may play a role in various diseases, including lung disorders like COPD. In our study, we investigated the preventive effect of NADH supplementation in an experimental model of COPD induced by cigarette smoke extract (CSE). N = 64 mice randomly distributed in eight groups were injected with NADH (two doses of 100 mg/kg or 200 mg/kg) or dexamethasone (2 mg/kg) before being exposed to CSE for up to 9 weeks. Additionally, NADH supplementation preserved lung antioxidant defenses by preventing the functional loss of key enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase, and the expression levels of glutathione (GSH) (n = 4, p < 0.001). It also reduced oxidative damage markers, such as malondialdehyde (MDA) and nitrites (n = 4, p < 0.001). A marked increase in tissue myeloperoxidase activity was assessed (MPO), confirming neutrophils implication in the inflammatory process. The latter was significantly ameliorated in the NADH-treated groups (p < 0.001). Finally, NADH prevented the CSE-induced secretion of cytokines such as Tumor Necrosis Factor alpha (TNF-α), IL-17, and IFN-y (n = 4, p < 0.001). Our study shows, for the first time, the clinical potential of NADH supplementation in preventing key features of COPD via its unique anti-inflammatory and antioxidant properties.


Assuntos
Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , NAD , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Animais , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Doença Pulmonar Obstrutiva Crônica/etiologia , NAD/metabolismo , Camundongos , Pneumonia/prevenção & controle , Pneumonia/metabolismo , Pneumonia/patologia , Injeções Intraperitoneais , Fumaça/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Masculino , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Citocinas/metabolismo , Pulmão/patologia , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Peroxidase/metabolismo
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