Effects of 7,8-Dihydroxyflavone on ER Stress, TXNIP/NLRP3 and Inflammation Related Markers in Tunicamycin-Treated Mice

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Şahin E., Sağlam Aksu N., Alver A.

CURRENT ISSUES IN MOLECULAR BIOLOGY, cilt.48, sa.11, ss.1114-1124, 2026 (SCI-Expanded, Scopus)

Özet

Background: Endoplasmic reticulum (ER) stress regulates cell fate through autophagy, apoptosis, and inflammatory pathways. In this study, we investigated the effects of 7,8-dihydroxyflavone (7,8-DHF) on ER stress-related inflammatory responses and examined its association with alterations in proteins involved in the thioredoxin-interacting protein (TXNIP)/NLRP3 signaling pathway. Materials and Methods: Thirty male C57BL/6 mice were divided into three groups (n = 10). ER stress was induced by a single intraperitoneal injection of tunicamycin (TUN, 0.5 mg/kg). A treatment group received 7,8-DHF (5 mg/kg/day) for 21 days following TUN administration, while controls received vehicle. Protein expression of GRP78, CHOP, TXNIP, and NLRP3 was assessed by Western blot. Serum IL-1β and IL-18 levels were measured by ELISA, and oxidative stress markers (SOD, CAT, and MDA) were evaluated spectrophotometrically. Results: TUN significantly increased GRP78, TXNIP, NLRP3, IL-1β, IL-18, and MDA levels. Treatment with 7,8-DHF significantly reduced CHOP, TXNIP, NLRP3, IL-1β, IL-18, and MDA levels compared with the TUN group. In addition, CAT activity was significantly increased following 7,8-DHF treatment. Conclusion: Overall, these findings suggest that DHF attenuated TUN-associated alterations in ER stress, oxidative stress, and inflammatory markers. However, further molecular studies are required to elucidate the underlying mechanisms.