Sulforaphane attenuates cisplatin‑induced acute kidney injury by inhibiting oxidative stress, inflammation and apoptosis via regulation of NRF2

Cisplatin‑induced acute kidney injury (CI‑AKI) is one of the most common comorbidities in patients undergoing chemotherapy, notably limiting the clinical use of cisplatin. However, the pathogenesis of CI‑AKI remains to be fully elucidated. Sulforaphane (SFN), a NRF2 agonist, exhibits anti‑inflammatory, antioxidant and anti‑apoptotic effects, thus SFN exerts protective effects in kidney injury diseases. However, the possible role and underlying mechanisms of SFN in CI‑AKI remain ambiguous. An in vivo model of CI‑AKI was constructed using C57BL/6 mice that were administered a single intraperitoneal cisplatin injection (20 mg/kg) and conditionally treated with SFN (10 mg/kg). Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were detected by biochemical analysis. Western blotting was performed to assess the expression of renal injury markers, as well as the apoptosis‑related proteins cleaved caspase‑3, caspase‑3, Bax and Bcl‑2. Furthermore, hematoxylin and eosin and periodic acid‑Schiff staining were employed to detect renal tissue lesions in mice, and TUNEL staining was used to evaluate the apoptosis of renal tissues in each group in vivo. Immunohistochemistry was used to assess the expression of inflammatory marker F4/80 in mouse renal tissues, and ELISA was used to detect the expressions of the inflammatory markers IL)‑1β, IL‑6 and tumor necrosis factor‑α (TNF‑α) in the serum of mice in each group. DCFH‑DA) analysis was used to detect reactive oxygen species (ROS) levels and biochemical analysis was used to evaluate the expression levels of malondialdehyde, superoxide dismutase and glutathione. Finally, western blotting and immunohistochemistry were performed to evaluate the expression of NRF2. An in vitro model of CI‑AKI was constructed using HK‑2 cells induced by cisplatin (10 µg/ml) that were conditionally treated with one or both of SFN (5 µM) and the NRF2 inhibitor ML385 (1.9 µM). Reverse transcription‑quantitative PCR was performed to evaluate the expression of NRF2. Cell Counting Kit‑8 assay was performed to assess the viability of HK‑2 cells in different groups, whereas flow cytometry was used to assess the apoptosis of HK‑2 cells in different groups. DCFH‑DA analysis was performed to evaluate the expression of ROS in different treatment groups. Furthermore, ELISA was used to evaluate the expressions of IL‑1β, IL‑6 and TNF‑α in each group. SFN notably decreased the serum levels of Scr and BUN and decreased the expression levels of kidney injury molecule‑1 and neutrophil gelatinase‑associated lipocalin in the cisplatin‑induced model group. Histopathological examination revealed attenuated renal structural damage and preserved tubular architecture in the SFN intervention group. Furthermore, SFN notably inhibited the apoptosis, inflammation and oxidative stress of renal tissues induced with cisplatin. Additionally, SFN markedly upregulated NRF2. In vitro, the NRF2 inhibitor ML385 partially attenuated the effects of SFN on the viability, apoptosis, inflammation and oxidative stress of HK‑2 model cells. The present study indicated that SFN exerted its nephroprotective effect through NRF2‑mediated anti‑inflammatory, antioxidant and anti‑apoptotic mechanisms, positioning SFN as a promising therapeutic candidate for clinical management of chemotherapy‑associated kidney injury.