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Article 2026 · 2 atıf

Sinapic acid attenuates vancomycin-induced hepatotoxicity in rats via modulation of ER stress (CHOP, IRE1, ATF-6, PERK), apoptotic pathways (caspase-3, Bax/Bcl-2, Apaf-1, cytochrome-c), and antioxidant defenses

Gur, Cihan, Ileriturk, Mustafa, Akaras, Nurhan, Kandemir, Fatih Mehmet

Özet

The present study aimed to investigate the protective properties of sinapic acid (SNP), one of the four most common hydroxycinnamic acids, whose activity against vancomycin (VCM)-induced hepatotoxicity, a glycopeptide antibiotic, has not been previously investigated. In the presented study, the protective properties of SNP against VCM-induced liver toxicity were investigated. For this purpose, VCM (200 mg/kg) and/or SNP (10 or 20 mg/kg) were given to Sprague-Dawley rats (n = 7) for 7 days. At the end of the study, biochemical, molecular, and histological analyses were performed on liver tissues. According to the data obtained, it was determined that VCM triggered oxidative stress, endoplasmic reticulum stress, autophagy, and apoptosis in liver tissue, activated metalloproteinases, and caused histological irregularities in the liver. On the other hand, after SNP treatment, it was observed that the activities of antioxidant enzymes SOD, CAT, and GPx increased, GSH stores were renewed, and MDA levels, an important indicator of lipid peroxidation, decreased. It was observed that oxidative DNA damage was alleviated and 8-OHdG levels were downregulated by suppressing oxidative stress. After SNP treatment, with the alleviation of ER stress, a decrease occurred in the relative mRNA transcript levels of ATF-6, PERK, IRE1, GRP-7,8, and CHOP sensors. Furthermore, SNP was seen to exhibit anti-apoptotic effects by decreasing Bax, Caspase-3, Apaf-1, and cytochrome-C and up-regulating Bcl-2 in the liver. Data also indicate that SNP suppresses MAPK-14, activates AKT2, and down-regulates metalloproteinases. In conclusion, it was observed that SNP may be an important protective agent against the hepatotoxicity of VCM.

Anahtar Kelimeler
Apoptosis Hepatotoxicity Oxidative stress Rat Sinapic acid Vancomycin INDUCED LIVER-DAMAGE GALLIC ACID INHIBITION FIBROSIS INJURY 4-PBA MMP-9
WoS Kategorileri
Anatomy & Morphology Cell Biology
Sürdürülebilir Kalkınma Amaçları
Künye
Dergi
TISSUE & CELL
Yıl
2026
Cilt
99
ISSN
0040-8166
DOI
10.1016/j.tice.2025.103255
WoS UID
WOS:001632869300001
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