Lipofundin-induced hyperlipidemia promotes oxidative stress and atherosclerotic lesions in new zealand white rabbits

Abstract

Atherosclerosis represents a major cause of death in the world. It is known that Lipofundin 20% induces atherosclerotic lesions in rabbits, but its effects on serum lipids behaviour and redox environment have not been addressed. In this study, New Zealand rabbits were treated with 2 mL/kg of Lipofundin for 8 days. Then, redox biomarkers and serum lipids were determined spectrophotometrically. On the other hand, the development of atherosclerotic lesions was confirmed by eosin/hematoxylin staining and electron microscopy. At the end of the experiment, total cholesterol, triglycerides, cholesterol-LDL, and cholesterol-HDL levels were significantly increased. Also, a high index of biomolecules damage, a disruption of both enzymatic and nonenzymatic defenses, and a reduction of nitric oxide were observed. Our data demonstrated that Lipofundin 20% induces hyperlipidemia, which promotes an oxidative stress state. Due to the importance of these phenomena as risk factors for atherogenesis, we suggest that Lipofundin induces atherosclerosis mainly through these mechanisms.

Figure 1

Histopathological analysis of rabbit's aortic tree. Eosin/hematoxylin staining reveals a normal morphology of aortas in control animals (a) and (c), while aortas of Lipofundin group show an intimal thickening, characterized by a vascular tissue architecture distortion and large extracellular spaces, probably filled with lipids (asterisks) (b) and (d). Arrow head: endothelial cells. Magnification 10× (a) and (b) and 40× (c) and (d). Scale bar, 20 μm.

Figure 2

Ultrastructural analysis. Panels (a) and (b) correspond to animals of control group, while panels (b), (c), (d), and (e) show the effects of Lipofundin administration on atherosclerotic lesion formation. EC: endothelial cells, EL: extracellular lipids, VSMC: vascular smooth muscle cells, N: nucleus, FC: foam cells, LV: lipid vacuolization, CF: collagen fibers, M: myofibroblasts. Scale bar 1 μm (a, b, c, d), 500 nm (e, f).