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. 2022 Aug;52(4):1378-1388.
doi: 10.55730/1300-0144.5445. Epub 2022 Aug 10.

Alpha-lipoic acid prevents atrial electrical and structural remodeling via inhibition of NADPH oxidase in a rabbit rapid atrial pacing model

Lei Chen  1 , Wen Gao  2 , Yameng Shao  1 , Chenggang Lı  3 , Yuan Lu  1
Affiliations

Alpha-lipoic acid prevents atrial electrical and structural remodeling via inhibition of NADPH oxidase in a rabbit rapid atrial pacing model

Lei Chen et al. Turk J Med Sci. 2022 Aug.

Abstract

Background: Alpha-lipoic acid (ALA) is a natural compound, one of the natural antioxidants with high activity. In the NADPH oxidase family, NADPH oxidase 4 (NOX4) is an important subunit participating in the production of ROS. NADPH oxidase 2 (NOX2) can form active NADPH oxidase complexes when binding to several other subunits in the cytoplasm, and NOX2 is its major functional subunit. Rapid atrial pacing (RAP) model was constructed to study the effects of ALA on electrical and structural remodeling in rabbits.

Methods: Thirty rabbits were divided into SHAM group, RAP group and ALA+RAP group. Their right atriums were paced at a speed of 600 beats/min for 12 h in the RAP and ALA+RAP groups, and the atrial effective refractory period (AERP) and AERP frequency adaptability were determined during the pace. In ALA+RAP group, ALA (30 mg/kg) was administered intraperitoneally daily to the rabbits for 3 days before RAP. Atrial tissue was collected from each group to detect malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS) to observe the effect of oxidative stress. The pathological structure of the atrial tissue was observed through hematoxylin-eosin (HE) staining. Ultrastructural changes in the atrial myocytes were observed by transmission electron microscopy (TEM), and the expression levels of Nox2 and Nox4 were detected by immunohistochemistry, western blot and ELISA.

Results: AERP gradually shortened, while ALA injection could remarkably delay this process. HE staining showed that the most of the nuclei appeared normal, the myocardial fibers did not show ruptures, and their arrangement was slightly ordered, and myofilament dissolution and mitochondrial swelling and deformation were rarely observed by TEM in the ALA+RAP group. Compared with the RAP group, the contents of MDA and ROS were reduced, SOD activity was enhanced, and the expression of NOX2 and NOX4 was decreased in the ALA+RAP group.

Discussion: ALA can inhibit atrial electrical remodeling and structural remodeling, and its mechanism may be related to inhibiting the activity of NADPH oxidase.

Keywords: NADPH oxidase; alpha-lipoic acid; oxidative stress,; rapid atrial pacing; reactive oxygen species.

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Figures

Figure 1
Figure 1
Light photomicrographs of the rabbit’s heart stained with hematoxylin and eosin (×200); (A) Myocardial fibers and nuclei in the SHAM group; (B) Myocardial fibers and nuclei in the RAP group; (C) Myocardial fibers and nuclei in the ALA+RAP group.
Figure 2
Figure 2
Ultrastructural changes of the heart with transmission electron microscopy; (A) The ultrastructure in the SHAM group; (B) The ultrastructural changes in the RAP group; (C) The ultrastructural changes in the ALA+RAP group.
Figure 3
Figure 3
a, p< 0.05 compared with the SHAM group; b, p< 0.05 compared with the RAP group.
Figure 4
Figure 4
a, p < 0.05 compared with the SHAM group; b, p < 0.05 compared with the RAP group.
Figure 5
Figure 5
Immunolocalization of NOX2 in myocardial tissue (×400); (A) Immunolocalization of NOX2 in the SHAM group; (B) Immunolocalization of NOX2 in the RAP group; (C) Immunolocalization of NOX2 in the ALA+RAP group.
Figure 6
Figure 6
a, p < 0.05 compared with the SHAM group; b, p < 0.05 compared with the RAP group.
See this image and copyright information in PMC

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