NADH intraperitoneal injection prevents massive pancreatic beta cell destruction in a streptozotocin-induced diabetes in rats.
Histochem Cell Biol
; 161(3): 239-253, 2024 Mar.
Article
en En
| MEDLINE
| ID: mdl-37943325
ABSTRACT
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Experimental
/
Células Secretoras de Insulina
/
Hiperglucemia
Límite:
Animals
Idioma:
En
Revista:
Histochem Cell Biol
Asunto de la revista:
CITOLOGIA
/
HISTOCITOQUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Argelia