Protective Effects of Trimetazidine and Dexmedetomidine on Liver Injury in a Mesenteric Artery Ischemia–Reperfusion Rat Model via Endoplasmic Reticulum Stress

Autor: Sedat Ciftel, Tolga Mercantepe, Riza Aktepe, Esra Pinarbas, Zulkar Ozden, Adnan Yilmaz, Filiz Mercantepe
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Biomedicines, Vol 12, Iss 10, p 2299 (2024)
Druh dokumentu: article
ISSN: 2227-9059
DOI: 10.3390/biomedicines12102299
Popis: Background/Objectives: Acute mesenteric ischemia can lead to severe liver damage due to ischemia–reperfusion (I/R) injury. This study investigated the protective effects of trimetazidine (TMZ) and dexmedetomidine (DEX) against liver damage induced by mesenteric artery I/R via endoplasmic reticulum stress (ERS) mechanisms. Methods: Twenty-four rats were divided into four groups: control, I/R, I/R+TMZ, and I/R+DEX. TMZ (20 mg/kg) was administered orally for seven days, and DEX (100 µg/kg) was given intraper-itoneally 30 min before I/R induction. Liver tissues were analyzed for creatinine, alanine ami-notransferase (ALT), aspartate aminotransferase (AST), thiobarbituric acid reactive substances (TBARS), and total thiol (TT) levels. Results: Compared with the control group, the I/R group presented significantly increased AST, ALT, TBARS, and TT levels. TMZ notably reduced creatinine levels. I/R caused significant liver necrosis, inflammation, and congestion. TMZ and DEX treatments reduced this histopathological damage, with DEX resulting in a more significant reduction in infiltrative areas and vascular congestion. The increase in the expression of caspase-3, Bax, 8-OHdG, C/EBP homologous protein (CHOP), and glucose-regulated protein 78 (GRP78) decreased with the TMZ and DEX treatments. In addition, Bcl-2 positivity decreased both in the TMZ and DEX treatments. Conclusions: Both TMZ and DEX have protective effects against liver damage. These effects are likely mediated through the reduction in ERS and apoptosis, with DEX showing slightly superior protective effects compared with TMZ.
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