Quinacrine, a PLA2 inhibitor, alleviates LPS-induced acute kidney injury in rats: Involvement of TLR4/NF-κB/TNF α-mediated signaling

Çomaklı S., Küçükler S., Değirmençay Ş., Bolat İ., Özdemir S.

INTERNATIONAL IMMUNOPHARMACOLOGY, cilt.126, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 126
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.intimp.2023.111264
  • Dergi Adı: INTERNATIONAL IMMUNOPHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Inflammation, Lipopolysaccharide, PLA2, Quinacrine, TLR4/NF-κB/TNF-α pathway
  • Atatürk Üniversitesi Adresli: Evet

Özet

Acute Kidney Injury (AKI) is a major factor in sepsis-related mortality and may occur due to lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria that triggers a systemic acute inflammatory response. Quinacrine's (QC) renoprotective properties in sepsis and the underlying mechanism, however, are still not fully understood. This study was done to investigate the anti-inflammatory, antioxidative, and anti-apoptotic effects of QC, a phospholipase A2 (PLA2) inhibitor, against LPS-induced AKI. Rats were randomly divided into five groups: control group, QC30 group, LPS group, LPS+QC 10 group, and LPS+QC 30 group. The rats were administered intraperitoneally QC (10 and 30 mg/kg) for 3 days (once a day) prior to injection of LPS (3 mg/kg). Six hours after the LPS injection, the histopathological changes, oxidative stress, inflammation, and apoptosis in the collected kidney tissues were detected by hematoxylin and eosin staining, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and immunohistochemistry staining, respectively. QC pretreatment could successfully attenuate LPS-induced AKI, as evidenced by a decrease in tissue histopathological injury. Meanwhile, QC alleviated LPS-induced kidney oxidative stress; it reduced MDA levels and increased levels of SOD, CAT, GPX, and GSH. LPS-induced elevations in kidney TLR4, NF-kappa B, TNF-alpha, IL-1 beta, IL-6, PLA2, caspase 3, and Bax contents were significantly attenuated in QC-treated groups. Our findings revealed a significant effect of QC: protecting against LPS-induced AKI through inhibition of PLA2 and decreasing inflammation, oxidative stress, and apoptosis. To treat LPS-induced AKI, QC may be an effective substance with an excellent protection profile.