AMPK-mediated autophagy is involved in the protective effect of canagliflozin in the vitamin D3 plus nicotine calcification model in rats.

Autor: Hewedy WA; Clinical Pharmacology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt. wafaa.hewedy@alexmed.edu.eg.; Al-Moassat Medical Campus, Elhadara, Clinical Pharmacology Department, Faculty of Medicine, Alexandria University, 21561, Alexandria, Egypt. wafaa.hewedy@alexmed.edu.eg., Abdulmalek SA; Bio-Screening and Preclinical Trial Lab, Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt., Ghareeb DA; Bio-Screening and Preclinical Trial Lab, Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt., Habiba ES; Clinical Pharmacology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Feb; Vol. 397 (2), pp. 873-888. Date of Electronic Publication: 2023 Jul 31.
DOI: 10.1007/s00210-023-02627-x
Abstrakt: Vascular calcification (VC) is a major risk factor for cardiovascular events. A mutual interplay between inflammation, oxidative stress, apoptosis, and autophagy is implicated in its development. Herein, we aimed to evaluate the potential protective effects of canagliflozin in a vitamin D3 plus nicotine (VDN) model of VC, and to explore potential mechanisms. VC was induced by VDN in adult male Wistar rats on day one. Then, rats were randomly assigned into three groups to receive canagliflozin (10 mg or 20 mg/kg/day) or its vehicle for 4 weeks. Age-matched normal rats served as a control group. After euthanization, aorta and kidneys were harvested for biochemical and histopathological evaluation of calcification. Aortic markers of oxidative stress, alkaline phosphatase (ALP) activity, runt-related transcription factor (Runx2) and bone morphogenic protein-2 (BMP-2) levels were determined. Additionally, the protein expression of autophagic markers, LC3 and p62, and adenosine monophosphate activated protein kinase (AMPK) were also assessed in aortic homogenates. Canagliflozin dose-dependently improved renal function, enhanced the antioxidant capacity of aortic tissues and reduced calcium deposition in rat aortas and kidneys. Both doses of canagliflozin attenuated ALP and osteogenic markers while augmented the expression of autophagic markers and AMPK. Histopathological examination of aortas and kidneys by H&E and Von Kossa stain further support the beneficial effect of canagliflozin. Canagliflozin could alleviate VDN-induced vascular calcification, in a dose dependent manner, via its antioxidant effect and modulation of autophagy. Further studies are needed to verify whether this effect is a member or a class effect.
(© 2023. The Author(s).)
Databáze: MEDLINE
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