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Effects of curcumin and CH5 curcuminoid on renovascular hypertension-induced matrix metalloproteinase (MMP)-2 and vascular remodeling

Grant number: 18/22474-8
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2019
Effective date (End): December 31, 2019
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal researcher:Elen Rizzi Sanchez
Grantee:Júlia Ramazza Maschio
Home Institution: Universidade de Ribeirão Preto (UNAERP). Campus Ribeirão Preto. Ribeirão Preto , SP, Brazil

Abstract

Mounting evidence have shown the important role of matrix metalloproteinase ((MMP)-2 to the systemic hypertension-induced vascular remodeling. Increased reactive oxygen species (ROS), which are involved with tissue remodelling in many cardiovascular disease, are the key factor to MMP-2 activation in experimental hypertension. At this sense, the reduction of the MMP-2 activity has been implicated as a beneficial effect of many antihypertensive drugs with antioxidant properties. The antihypertensive and antioxidant actions of curcumin are well known. In addition, the molecular docking study showed that curcumin can interact directly with MMP-2. Despite of the curcumin benefits described, this polyphenol has low bioavailability, but structural modifications carried out to potentiate its beneficial effects generated the curcuminoids. The CH-5 analog was developed by the Prof. Dr. Luis Octavio Regasini and the research group from the Prof. Dr. Mozart de Azevedo Marins showed that this curcuminoid had potent anticancer effects in cell culture that were associated with MMP-2 inhibition. However, whether this new CH-5 curcuminoid may have greater benefits effects than those observed by the simple curcumin treatment in the hypertension is completely uncertain. Thus, the aims of the present study are to evaluate and to compare the effects of the curcumin and the CH-5 curcuminoid treatment on the L-name (N(É)-nitro-L-arginine methyl ester, nitric oxide synthase inhibitor)-induced hypertension, vascular remodeling, increased MMP-2 and oxidative stress. Control and hypertensive animals will be treated with curcumin and CH-5 curcuminoid during 2 weeks. The systolic blood pressure will be monitored weekly by tail plethysmography. Histological changes in aortas will be examined in sections of 4 ¼m stained with hematoxylin/eosin. Vascular oxidative stress will be evaluated using Dihydroethidium (DHE). Aortic MMP-2 levels and gelatinolytic activity will be determined using gelatin and in situ zymography assays, respectively. The curcumin and CH-5 effects on MMP-2 activity will also be determined by in vitro gelatin zymography assay.