Impact of glucotoxicity induced <i>in vivo</i> and <i>in vitro</i> in <i>Psammomys obesus</i>

Abstract

Objective: Chronic hyperglycemia characteristic of type diabetes 2 is responsible for the accelerated atherosclerosis with increased cardiovascular risk. In this study, we will propose to analyze the effect of a long-term of glucotoxicity in vivo in Psammomys obesus by addition of sucrose to 30% for 11 months and in vitro study of adventitial fibroblasts in the presence of D-glucose 0.6% for 7 days. Materials and methods: Evaluation of plasma biochemical parameters was carried out at the initial time and at the end of experiment. At autopsy, a morphological study of the aorta was performed after fixation in aqueous Bouin and staining with Masson's trichrome. The experimental glucotoxicity is induced by incubation of fibroblasts in DMEM enriched with D-glucose at 0.6% for 7 days. The impact of glucotoxicity is assessed in the intracellular compartments through dosage of total nitrite and malondialdehyde, a product of lipid peroxidation, and thanks to a morphological assay after fixation of cells with aqueous bouin and blood staining with May Grünwald Giemsa. The evaluation of cell proliferation is accomplished by cell counting. Collagens I and III of the extracellular compartment are characterized by SDS-PAGE. Results: Animals subjected to sucrose showed hyperglycemia associated with hyperinsulinemia, dyslipidemia, hyperproteinemia, increased CPK and VLDL-LDL and decreased HDL. Histology of aortas revealed endothelial cells hypertrophy, severe disorganization of intima and media. In the presence of glucose, the proliferation of fibroblasts increases very significantly (P = 2.34 × 10