Quinic acid attenuates cisplatin-induced acute kidney injury by modulating inflammatory cytokines, oxidative stress, apoptosis, and the Nrf2/HO-1/NQO1 pathway in rats

Abstract

Abstract Background The nephrotoxicity induced by cisplatin (Cis) is mediated by oxidative stress, inflammation, and apoptosis, which limit the clinical utility of this commonly used chemotherapeutic drug. Natural polyphenolic compounds such as quinic acid (QA) have cytoprotective and antioxidant properties. This study evaluated the protective effect of QA against cisplatin-induced acute kidney injury (AKI) in rats and its impact on the associated oxidative, inflammatory, apoptotic, and Nrf2/HO-1/NQO1 pathways. Methods Forty male Wistar rats were randomly divided into five groups (n = 8): Control, Cis (7.5 mg/kg, i.p.), Cis + QA was administered orally at doses of 25, 50, or 100 mg/kg once daily for 14 days before the cisplatin challenge. Biochemical markers (BUN, creatinine, KIM-1, NGAL), oxidative stress indices (MDA, NO, GSH, TAC, SOD, CAT, GPx), inflammatory cytokines (TNF-α, IL-1β), apoptotic gene expression (Bax, Bcl-2, caspase-3), and Nrf2 pathway proteins (Nrf2, HO-1, NQO1) were assessed. Renal histopathology was evaluated using blinded scoring. Results Cisplatin caused severe renal dysfunction, oxidative imbalance, inflammation, and apoptosis, along with the suppression of Nrf2/HO-1/NQO1 signaling. QA, particularly at doses of 50 and 100 mg/kg, significantly improved serum renal markers, restored antioxidant capacity, reduced MDA and NO levels, downregulated TNF-α and IL-1β, modulated apoptotic gene expression toward cell survival, and enhanced Nrf2-pathway protein levels. Histological injury scores were significantly lower in groups treated with QA. Conclusions The antioxidant, anti-inflammatory, anti-apoptotic, and Nrf2-pathway-modulating properties of quinic acid markedly attenuate cisplatin-induced AKI. Further mechanistic and translational research on QA to evaluate its potential as a nephroprotective adjunct is warranted.