AKT SIGNALING AND NITRIC OXIDE SYNTHASE AS POSSIBLE MEDIATORS OF THE PROTECTIVE EFFECT OF N-ACETYL-L-CYSTEINE IN PREDIABETES INDUCED BY SUCROSE

CASTRO MC; VILLAGARCÍA H; DI SARLI GUTIÉRREZ L; GONZÁLEZ ARBELÁEZ LF; SCHINELLA G; MASSA ML; FRANCINI F

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Lugar: Basel; Año: 2024 vol. 25 p. 1215 - 1227

1422-0067

the aim of this work was to evaluate possible mechanisms involved in the protective effect of N-acetyl-L-cysteine (NAC) on hepatic endocrine-metabolic, oxidative stress and inflammatory changes in prediabetic rats. For that, normal male Wistar rats (60 days old) were fed 21 days with sucrose 10% in the drinking water and 5 days of NAC administration (50 mg/kg, i.p.) and thereafter, we determined: serum glucose, insulin, transaminases, uric acid, and triglyceride levels; hepatic fructokinase and glucokinase activities, glycogen content, lipogenic gene expression; enzymatic and non-enzymatic oxidative stress, insulin signaling pathway and inflammatory markers. Results showed that alterations evinced in sucrose fed rats (hypertriglyceridemia, hyperinsulinemia, and high liver fructokinase activity together with increased liver lipogenic gene expression and ox-idative stress and inflammatory markers were prevented by NAC administration. P-endothelial nitric oxide synthase (P-eNOS)/eNOS and pAKT/AKT ratios, decreased by sucrose ingest, were restored after NAC treatment. In conclusion, the results suggest that NAC administration improve glucose homeostasis, oxidative stress, and inflammation in prediabetic rats probably mediated by modulation of the AKT/NOS pathway. Administration of NAC may be an effective complemen-tary strategy to alleviate or prevent oxidative stress and inflammatory responses observed in type 2 diabetes at early stages of its development (prediabetes).