Scopus
Proanthocyanidin alleviates vancomycin-induced kidney injury via modulation of Nrf2/Keap1/HO1, Bax/Bcl-2/Caspase-3, and TLR4/MyD88/NF-κB pathways
Tissue and Cell · Ağustos 2026
Makale Bilgileri
DergiTissue and Cell
Yayın TarihiAğustos 2026
Cilt / Sayfa101
Scopus ID2-s2.0-105032810365
Özet
Vancomycin (VAN), a complex tricyclic glycopeptide antibiotic, is currently utilized primarily in the therapy of bacterial infections for drug resistant Gram-positive bacteria. However, its clinical usage is restricted due to its association with renal toxicity at high doses. The potential efficacy of proanthocyanidin (PRO) on vancomycin-associated nephrotoxicity remains unclear. This current research aimed to assess the potential protective impacts of proanthocyanidin against vancomycin-associated nephrotoxicity and to assess the underlying mechanism. Wistar albino rats were split into 4 groups (8 rats per group) at random: Control (C), PRO (200 mg/kg/po), VAN (200 mg/kg, i.p., twice a day), and VAN+PRO (200 mg/kg, i.p., twice a day VAN, 200 mg/kg/po PRO). All administrations were applied for 7 days. PRO treatment alleviated VAN-induced oxidative stress by increasing antioxidants (SOD, CAT, GPx) and reducing elevated MDA levels, a marker of lipid peroxidation. PRO elevated antioxidant activity by triggering the Nrf2/Keap1/HO1 signaling pathway. VAN-induced elevations in proapoptotic p53, Bax, and caspase-3 levels were diminished by PRO, while the decrease in antiapoptotic Bcl-2 levels elevated, thereby alleviating apoptosis. Furthermore, VAN-induced increases in TLR4, MyD88, NF-κB, iNOS, IL-18, and TNF-α levels were reduced by PRO, while IL-10 levels increased, reducing the inflammatory response. PRO treatment caused an upregulation of PPARγ levels and a downregulation of GRP78 levels. Furthermore, PRO treatment preserved kidney function and structural integrity. Considering all these findings, proanthocyanidin may be effective in reducing vancomycin-induced renal injury by diminishing oxidative stress, inflammation, apoptosis, and ER stress in vancomycin-induced renal damage and activating protective cellular mechanisms through Nrf2/HO1 and PPARγ, and therefore can be considered an effective treatment option.
Yazarlar (10)
1
G. Akcakavak
2
Ozhan Karatas
3
Filiz Kazak Akcakavak
ORCID: 0000-0002-9065-394X
4
Aysenur Tural Cifci
ORCID: 0000-0003-1585-3359
5
Ahmed A.J. Jabbar
ORCID: 0000-0001-9689-4018
6
Omer Kirgiz
7
Halil Alakus
ORCID: 0000-0001-9265-2310
8
Ibrahim Alakus
ORCID: 0000-0002-2031-7035
9
Fatma Ceren Kirgiz
ORCID: 0000-0002-8454-5336
10
Mehmet Tuzcu
Anahtar Kelimeler
Antioxidant
Apoptosis
Inflammatory process
Kidney
Vancomycin
Kurumlar
Aksaray Üniversitesi
Aksaray Turkey
Cumhuriyet Üniversitesi
Sivas Turkey
Erbil Polytechnic University
Erbil Iraq
Mustafa Kemal Üniversitesi
Antakya Turkey
Selçuk Üniversitesi
Selçuklu Turkey