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Adv Pharm Bull. 2024;14(2): 412-418.
doi: 10.34172/apb.2024.039
PMID: 39206399
PMCID: PMC11347735
  Abstract View: 549
  PDF Download: 207

Research Article

Docosahexaenoic Acid Reduced Vascular Endothelial Cell Injury in Diabetic Rats Via the Modulation of Autophagy

Aysan Eslami Abriz 1 ORCID logo, Atefeh Araghi 2, Mahdieh Nemati 1, Maryam Taghavi Narmi 3, Mahdi Ahmadi 1, Fatemeh Abedini 3, Rana Keyhanmanesh 3,4, Fariba Ghiasi 3,4, Reza Rahbarghazi 1,5* ORCID logo

1 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Faculty of Veterinary Medicine, Amol University of Special Modern Technologies, Amol, Iran.
3 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
5 Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
*Corresponding Author: Reza Rahbarghazi, Email: rahbarghazir@tbzmed.ac.ir, Email: rezarahbardvm@gmail.com

Abstract

Purpose: Among varied ω-3 polyunsaturated fatty acid types, the therapeutic properties of docosahexaenoic acid (DHA) have been indicated under diabetic conditions in different cell lineages. Here, we investigated the anti-diabetic properties of DHA in rats with type 2 diabetes mellitus (D2M) focusing on autophagy-controlling factors.

Methods: D2M was induced in male Wistar rats using a single dose of streptozocin (STZ) and a high-fat diet for 8 weeks. On week 2, diabetic rats received DHA 950 mg/kg/d until the end of the study. After that, rats were euthanized, and aortic and cardiac tissue samples were stained with H&E staining for histological assessment. The expression of adhesion molecules, ICAM-1 and VCAM-1, was measured in heart samples using real-time PCR analysis. Using western blotting, protein levels of BCLN1, LC3, and P62 were measured in D2M rats pre- and post-DHA treatment.

Results: Data showed intracellular lipid vacuoles inside the vascular cells, and cardiomyocytes, after induction of D2M and DHA reduced intracellular lipid droplets and in situ inflammatory response. DHA can diminish increased levels of ICAM-1 in diabetic conditions (PControl vs. D2M rats=0.005) and reach near-to-control values (PControl vs. D2M rats=0.28; PD2M rats vs. D2M rats+DHA=0.033). Based on western blotting, D2M slightly increased the BCLN1 and LC3-II/I ratio without affecting P62. DHA promoted the LC3II/I ratio (P=0.303) and reduced P62 (PControl vs. D2M rats+DHA =0.0433; PD2M vs. D2M rats+DHA=0.096), leading to the completion of autophagy flux under diabetic conditions.

Conclusion: DHA can reduce lipotoxicity of cardiovascular cells possibly via the activation of adaptive autophagy response in D2D rats.

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Submitted: 16 Dec 2023
Revision: 08 Mar 2024
Accepted: 17 Mar 2024
ePublished: 20 Mar 2024
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