Matrix Metalloproteinases and Their Role in Mechanisms Underlying Effects of Quercetin on Heart Function in Aged Zucker Diabetic Fatty Rats

Abstract

Several mechanisms may contribute to cardiovascular pathology associated with diabetes, including dysregulation of matrix metalloproteinases (MMPs). Quercetin (QCT) is a substance with preventive effects in treatment of cardiovascular diseases and diabetes. The aim of the present study was to explore effects of chronic QCT administration on changes in heart function in aged lean and obese Zucker Diabetic Fatty (ZDF) rats and that in association with MMPs. Signaling underlying effects of diabetes and QCT were also investigated. In the study, we used one-year-old lean and obese ZDF rats treated for 6 weeks with QCT. Results showed that obesity worsened heart function and this was associated with MMP-2 upregulation, MMP-28 downregulation, and inhibition of superoxide dismutases (SODs). Treatment with QCT did not modulate diabetes-induced changes in heart function and MMPs. However, QCT activated Akt kinase and reversed effects of diabetes on SODs inhibition. In conclusion, worsened heart function due to obesity involved changes in MMP-2 and MMP-28 and attenuation of antioxidant defense by SOD. QCT did not have positive effects on improvement of heart function or modulation of MMPs. Nevertheless, its application mediated activation of adaptive responses against oxidative stress through Akt kinase and prevention of diabetes-induced negative effects on antioxidant defense by SODs.

ZDF (fa/fa) rats show increasing heterogeneity in main parameters during ageing, as confirmed by biometrics, oxidative stress markers and MMP activity

“…The increased activity of MMP2 proves the left ventricular tissue remodelling in ZDF (fa/fa) DIA and ZDF (fa/fa) FAT rats. Higher activity of MMP2 in the left ventricular tissue was also found in 1‐year‐old ZDF compared with lean ZDF rats (Botanska et al., 2021). Given that we were not able to detect MMP9 activity in the heart tissue using gelatin zymography, this led us to the hypothesis that there was no serious pathology.…”

The Anti-Cytokine Storm Activity of Quercetin Zinc and Vitamin C Complex

“…However, there were significant differences between groups B and C ( p < 0.05). The results in group C may be attributed to the ability of LPS to activate toll-like receptor 4 (TLR4) that, in turn, leads to activate the nuclear factor kappa light chain kappa factor (NF- ҡ B) and MAPK kinase pathway [ 15 ]; subsequently, they lead to the expression of many proinflammatory cytokines and a significant increase in the production of reactive oxygen species (ROS) and synthesis of nitric oxide (NO) and prostaglandin E2 (PGE2) [ 16 ]. Moreover, activation of the nude-like receptor (NLR), Janus kinases (JAKs)/signal transducer, transcription proteins, and JAK-STAT inflammatory pathways lead to elevated levels of IL-1 and IL-6, thereby cytokine storm produced [ 17 ].…”

Quercetin alleviates diastolic dysfunction and suppresses adverse pro-hypertrophic signaling in diabetic rats

“…The E/A ratio dysregulation is a sensitive matter regarding diastolic function and highly depends on the underlying condition, both reversal and increase indicate an altered function, in our case, the increased E/A ratio seems to be leaning more toward the restrictive filling pattern ( 39 ). As the plasma triglycerides, cholesterol and LDL cholesterol of aged ZDFs remained unchanged by treatment, although raised by diabetes ( 31 ), it is less likely that the protective mechanisms by which Que contributes to the improvement of LVDD lies in the improvement of lipid metabolism. To bring more insight into the degree of present LVDD,we evaluated proBNP expression.…”

“…plasma glucose levels) and metabolic parameters (e.g. lipid profile) have been already presented elsewhere ( 29 – 31 ). During the course of the study protocol, all experiments concerning animals were performed accordingly to the rules issued by the State Veterinary Administration of the Slovak Republic, legislation No 377/2012 and with the regulations of the Animal Research and Care Committee of the Centre of Experimental Medicine SAS—Project no.…”