Article 2025 · 4 atıf

Hesperidin ameliorates vancomycin-induced kidney injury via multipathway modulation: Nrf-2/HO-1, Caspase-3/Bax/Bcl-2, ATF-4, KIM-1 and improved renal tissue function

Gencer, Selman, Simsek, Hasan, Akaras, Nurhan, Ileriturk, Mustafa, Gur, Cihan, Kucukler, Sefa, Kankilic, Nazim Abdulkadir, Kandemir, Fatih Mehmet

Özet

Vancomycin (VCM) is a therapeutic agent used to treat drug-resistant gram-positive bacteria. However, its highdose use is associated with nephrotoxicity, limiting its clinical application. Hesperidin (HES), a flavonoid naturally found in citrus fruits, exhibits various biological and pharmacological activities, including antiinflammatory, antioxidant, and anticancer effects. While HES has been shown to exert protective effects in several organ systems, its potential role in preventing VCM-induced nephrotoxicity remains unclear. This study investigates whether HES can mitigate VCM-induced renal damage through its antioxidant and antiinflammatory properties. VCM was administered intraperitoneally at a dose of 200 mg/kg for seven days. HES (100 mg/kg and 200 mg/kg) was administered orally for seven days. Biochemical, and molecular methods were used to investigate indicators of oxidative stress, ER stress damage, apoptotic and autophagic death in kidney tissue. Additionally, histological methods were used to determine the structural and functional characteristics of kidney tissue. HES treatment alleviated VCM-induced oxidative stress by increasing antioxidants (SOD, CAT, GPx, GSH) and reducing increased MDA levels, a marker of lipid peroxidation. In addition, HES increased antioxidant activity by activating the Nrf2 signaling pathway. VCM-induced increases in apoptotic Bax, Caspase3, and P53 were reduced by HES, while the decreased level of antiapoptotic Bcl-2 was increased. HES reduced VCM-induced ER stress damage by reducing the levels of ATF-4, ATF-6, eIF2-alpha, and CHOP. HES treatment attempted to preserve kidney function and structural integrity. Overall, HES was effective in reducing VCMinduced nephrotoxicity damage and may be an effective treatment option.

Anahtar Kelimeler

Apoptosis Autophagy ER stress Hesperidin Vancomycin OXIDATIVE STRESS APOPTOSIS INFLAMMATION ZINGERONE ACID

WoS Kategorileri

Pharmacology & Pharmacy

Sürdürülebilir Kalkınma Amaçları

Sağlık ve Kaliteli Yaşam

Künye

Dergi: BIOCHEMICAL PHARMACOLOGY
Yıl: 2025
Cilt: 240
ISSN: 0006-2952
eISSN: 1873-2968
DOI: 10.1016/j.bcp.2025.117131
WoS UID: WOS:001529436900003

Yayını aç (DOI)