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Diabetes and hypercholesterolemia experimental study on inhibition of liver fibrosis by angiotensin converting enzymes


Journal of Cardiology & Current Research
Daniel R Pomaro,1 Francisco AH Fonseca,2 Anita LR Saldanha,3 Valeria P Lanzoni,1 Dulce E Casarini,2 Ana Paula Pantoja Margeotto,3 André LV Gasparoto,4 Tereza Luiza Bellincanta,3 Tania Leme da Rocha Martinez,3 Silvia SM Ihara1

Abstract

Purpose: The aim of this study was to evaluate the effect of angiotensin-converting enzyme (ACE)inhibitor on the liver histopathological changes in hypercholesterolemic and diabetic rabbits.

Methods: New Zealand rabbits were treated by a single dose of alloxan (100mg iv) and were fed a chow with 0.5% cholesterol for 12weeks. The animals were divided into four groups according to the level of blood glucose: ≥250 mg/dL for groups I (n =10) and II (n=8) or <250mg/dL for groups III (n=12) and IV (n=12) and the groups II and IV were treated with an ACE inhibitor, quinapril (30mg/d) added to the diet. Total serum cholesterol and glucose levels and ACE activity were determined. Histological analysis was performed on liver samples stained with hematoxylin and eosin and picrosirius red. Liver fibrosis was analyzed by Metavir classificationand was quantified by Image Tool software in picrosirius polarized images.

Results: The four groups were hypercholesterolemic, without significant statistical differences in cholesterol levels among them. ACE activity was lower in the plasma of animals treated with ACE inhibitor (groups II and IV, p<0,01). We observed lower collagen area determined histomorphometrically in the both groups treated with ACE inhibitors, although onlyin the group with blood glucose control, there have been statistically significant.(p<0.05; group IV

Conclusion: Our results suggest a benefit in liver protection achieved by the use of an ACE inhibitor in hypercholesterolemic and diabetic rabbits. This study highlights the importance of the renin-angiotensin system in protecting organs affected by high levels of lipids and glucose.

Keywords

liver fibrosis, ace inhibitor, rabbit, diabetes, cholesterol, ACE, angiotensin-converting enzyme, ACEI, angiotensin-converting enzyme inhibitors, AT1,angiotensin II type 1 receptor, HSC, hepatic stellate cell, RAS, renin-angiotensin system

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