Open Access

ARTICLE

20-Hydroxyecdysone Partially Alleviates Ischemia/Reperfusion-Induced Damage of Mouse Hind Limb Skeletal Muscle

Alena A. Semenova^1,*, Anastasia D. Igoshkina¹, Alena A. Cherepanova¹, Natalia V. Mikina¹, Anastasia E. Stepanova¹, Оlga E. Krasnoshchekova¹, Vyacheslav A. Sharapov¹, Rimma G. Savchenko², Lyudmila V. Parfenova², Mikhail V. Dubinin¹

1 Department of Biochemistry, Cell Biology, and Microbiology, Mari State University, Yoshkar-Ola, 424001, Russia
2 Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, 450075, Russia

* Corresponding Author: Alena A. Semenova. Email:

(This article belongs to the Special Issue: Mitochondrial Dysfunction in Metabolic and Neuromuscular Diseases: Mechanisms and Therapeutic Strategies)

BIOCELL 2025, 49(3), 437-450. https://doi.org/10.32604/biocell.2025.061798

Received 03 December 2024; Accepted 20 February 2025; Issue published 01 April 2025

Abstract

Objectives: Skeletal muscle ischemia/reperfusion injury (IRI) occurs as a result of a marked reduction in arterial perfusion to a limb and can lead to tissue death and threaten limb viability. This work assessed the effects of 20-hydroxyecdysone (20E) on hindlimb skeletal tissue following tourniquet-induced ischemia/reperfusion injury. Methods: Animals were divided into 4 groups—control group (Control), Control + 20E (C + 20E), mice with IRI (IRI), and mice with IRI + 20E (IRI + 20E). IRI was modeled by applying a tourniquet to the hind limb for 2 h with reperfusion for 1 h. 5 mg/kg of 20E was administered intraperitoneally for 14 days. Afterward, the physical activity of mice, the histological structure of the quadriceps femoris, the expression of genes encoding proteins induced by hypoxia and involved in tissue adaptation to ischemia, and the functional parameters of skeletal muscle mitochondria were assessed. Results: It was shown that IRI of the limbs leads to functional disorders, depression of muscle function, accumulation of malondialdehyde (MDA) in mitochondria, and a decrease in their Ca²⁺ buffering capacity, as well as an increase in the expression of HIF-1α, VGEF-A, PGC1α and PDGF-BB genes associated with adaptation to ischemia. 20E reduced the intensity of degenerative processes in skeletal muscles, which was expressed in a decrease in the number of centrally nucleated fibers. Analysis of gene expression levels indicated a high degree of adaptation of animals to IRI. 20E reduced the level of MDA in mitochondria, but did not affect the rate of respiration and calcium retention capacity of organelles both in normal conditions and during IRI. Conclusion: 20E partially alleviates the skeletal muscle damage caused by IRI and can be used as part of combination therapy.

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