Author(s)

Berdja Sihem, Smail Leila, Othmani Kheira, Neggazi Samia, Hamlat Nadjiba, Boumaza Saliha, Sahraoui Abdelhamid, Kacimi Ghouti, Haffaf El Mahdi, Benazzoug Yasmina, Aouichat Bouguerra Souhila

.
Laboratory of Cellular and Molécular Physiopathology, Institute of Natural Sciences, University of Technological Sciences, Houari Boumediene, Algiers, Algeria.

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^-5), the rate of malonaldehyde, nitrite and total density of chains α2 (I) and α1 (I + III) extra-cellular collagens I and III increased significantly. After staining, the cells showed hypertrophy, vacuolation of cytoplasm and chromatin condensation with nuclear fragmentation, indicative of apoptosis. Conclusion: The glucotoxicity induced in vivo and in vitro is responsible for major structural and metabolic alterations leading to the acceleration of the atherosclerotic process.

Psammomys Obesus; Aorta; Adventitial Fibroblasts in Culture; DT2; Glucotoxicity; Extracellular Matrix; Oxidative Stress

Sihem, B. , Leila, S. , Kheira, O. , Samia, N. , Nadjiba, H. , Saliha, B. , Abdelhamid, S. , Ghouti, K. , Mahdi, H. , Yasmina, B. and Souhila, A. (2012) Impact of glucotoxicity induced in vivo and in vitro in Psammomys obesus. Journal of Diabetes Mellitus, 2, 59-71. doi: 10.4236/jdm.2012.21010.