Effects of Ellagic Acid and Berberine on Skeletal Muscle in HindLimb Ischemia Reperfusion Injury


Tekin E., Kaya A. K., Küçük A., Arslan M., Özer A., Demirtaş H., ...More

Turkish Society of Physiological Sciences, 49th Turkish Physiology Congress, İzmir, Turkey, 6 - 09 November 2024, pp.64

  • Publication Type: Conference Paper / Summary Text
  • Doi Number: 10.1111/apha.70004
  • City: İzmir
  • Country: Turkey
  • Page Numbers: pp.64
  • Kütahya Health Sciences University Affiliated: Yes

Abstract

AIM: Hind limb ischemia/reperfusion (I/R) injury is a serious clinicalcondition. The aim of this study is to compare the effects of ellagicacid and berberine on oxidative stress and cell death pathways inhind limb I/R injury model.

METHODS: Thirty-five male Sprague-Dawley rats were randomlydivided into five groups (n=7 each): Sham, I/R, Ellagic Acid+I/R,Berberine+I/R, and Ellagic Acid+Berberine+I/R. The infrarenalabdominal aorta was clamped and reperfused during 2 hoursrespectively. At the 75th minute of ischemia, ellagic acid (100mg/kg, ip) and berberine (200 mg/kg, ip) were administered.Oxidative stress markers (MDA, GSH, SOD, CAT), apoptosis(Cleaved caspase-3, Bax, Bcl-2) and pyroptosis (NLRP3, NRF2,Gasdermin D) pathways were evaluated. Muscle tissue washistopathologically assessed with hematoxylin-eosin staining.

RESULTS: Histopathological assessment showed significantincreases in muscle atrophy/hypertrophy, degeneration/congestion, nuclear internalization/oval-central nucleus,fragmentation/hyalinization, and leukocyte infiltration in the I/Rgroup. Ellagic acid and berberine reduced them, yielding resultsclose to the sham group. Bax levels increased in I/R group, whileellagic acid and berberine reduced Bax levels. Bcl-2 levelsdecreased in I/R group but reached normal levels with ellagic acidand berberine. The Bax/Bcl-2 ratio was highest in the I/R group, butellagic acid and berberine normalized it. NRF2 levels decreased,while NLRP3 and Gasdermin D levels increased in I/R group; ellagicacid and berberine normalized these levels. MDA levels werereduced, while GSH, SOD, and CAT levels were increased withellagic acid and berberine compared to I/R group.

CONCLUSIONS: Ellagic acid and berberine showed beneficialeffects on apoptosis, pyroptosis, and oxidative processes in hindlimb I/R injury. The combined use of these antioxidants resulted inmore effective outcomes in Bax/Bcl-2 ratio and some histologicaldamage parameters. Ellagic acid and berberine, either separatelyor in combination, can be considered potential therapeutic agentsfor hind limb I/R injury.