4.3 Article

Ezetimibe attenuates experimental diabetes and renal pathologies via targeting the advanced glycation, oxidative stress and AGE-RAGE signalling in rats

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ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY
卷 129, 期 4, 页码 831-846

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TAYLOR & FRANCIS LTD
DOI: 10.1080/13813455.2021.1874996

关键词

Ezetimibe (EZ); diabetes; advanced glycation endproducts (AGEs); AGE-RAGE-signalling; carboxymethyl-lysine (CML); fluorescent AGEs; HMG-R activity; diabetic nephropathy

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The study demonstrates the protective effects of ezetimibe (EZ) against AGEs-related pathologies in experimental diabetes, including improved biochemical markers, regulation of gene expression, maintenance of redox status, and protection of renal histopathological features.
The current in-vivo study was premeditated to uncover the protective role of ezetimibe (EZ) against advanced glycation endproducts (AGEs)-related pathologies in experimental diabetes. Our results showed that EZ markedly improved the altered biochemical markers of diabetes mellitus (DM) (FBG, HbA1c, insulin, microalbumin, and creatinine) and cardiovascular disease (in-vivo lipid/lipoprotein level and hepatic HMG-CoA reductase activity) along with diminished plasma carboxymethyl-lysine (CML) and renal fluorescent AGEs level. Gene expression study revealed that EZ significantly down-regulated the renal AGEs-receptor (RAGE), nuclear factor-kappa B (NF kappa B-2), transforming growth factor-beta (TGF-beta 1), and matrix metalloproteinase-2 (MMP-2) mRNA expression, however, the neuropilin-1 (NRP-1) mRNA expression was up-regulated. In addition, EZ also maintained the redox status via decreasing the lipid peroxidation and protein-bound carbonyl content (CC) and increasing the activity of high-density lipoprotein (HDL)-associated-paraoxonase-1 (PON-1) and renal antioxidant enzymes as well as also protected renal histopathological features. We conclude that EZ exhibits antidiabetic and reno-protective properties in diabetic rats.

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