The protective role of iron chelation and zinc supplements in atherosclerosis induced in New Zealand white rabbits: A nuclear microscopy study

Abstract

The protective properties of iron chelator desferal and zinc supplements on atherosclerosis induced in New Zealand white rabbits were investigated using nuclear microscopy, incorporating particle induced X-ray emission (PIXE), Rutherford backscattering spectrometry (RBS) and scanning transmission ion microscopy (STIM). Firstly, we examined the effects of the desferal (desferrioxamine - a chelator which forms a stable complex with ferric iron) on atherosclerosis progression and lesion iron content in cholesterol-fed New Zealand white rabbits. Rabbits were fed with a 1% w/w cholesterol diet (HFD - high fat diet) for either 8 weeks (with the last 5 weeks injected daily with desferal), or for 12 weeks (with the last 9 weeks injected with desferal). Controls were injected with saline. A significant reduction in average lesion area (p = 0.038) was observed in the 12-week treated animals as compared with the 12-week controls. The average lesion iron level of the 12 week treated animals (58 ppm dry weight) was significantly lower (p = 0.03) than for the 12-week control animals (95 ppm dry weight). No reduction in lesion area or iron content was observed in the 8 week treated animals compared with controls, and no change in lesion zinc concentration was observed for either group. This data is consistent with the concept that iron contributes to the early stages in the development of atherosclerosis and that removal of iron from the lesion retards the progression of the disease. Secondly, the effect of zinc supplements on atherosclerotic lesion growth was examined. The rabbits in the test group received a 1% w/w cholesterol diet with Zn supplements for 8 weeks and the rabbits in the control group were fed only with a 1% w/w cholesterol diet for the same period of time. Lesion area analyses using light microscopy showed that the average lesion area was 1.0 mm2 for the test models compared with 3.0 mm2 for the control group models (p = 0.0045). Elemental analysis of the lesion and adjacent artery wall showed that the average zinc level remained the same for both the lesion and the artery wall for both test and control models, whilst the iron levels are reduced from 43 ppm to 31 ppm (in the lesion) and from 17 ppm to 6 ppm (in the artery wall). This raises the possibility that zinc may act as an endogenous protective factor against atherosclerosis by reducing iron levels.