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