Abstract
Acute kidney injury (AKI) is a dose-limiting side effect of cisplatin therapy in cancer patients. However, effective therapies for cisplatin-induced AKI are not available. Oxidative stress, tubular cell death, and inflammation are known to be the major pathological processes of the disease. 6-Shogaol is a major component of ginger and exhibits anti-oxidative and anti-inflammatory effects. Accumulating evidence suggest that 6-shogaol may serve as a potential therapeutic agent for various inflammatory diseases. However, whether 6-shogaol exerts a protective effect on cisplatin-induced renal side effect has not yet been determined. The aim of this study was to evaluate the effect of 6-shogaol on cisplatin-induced AKI and to investigate its underlying mechanisms. An administration of 6-shogaol after cisplatin treatment ameliorated renal dysfunction and tubular injury, as shown by a reduction in serum levels of creatinine and blood urea nitrogen and an improvement in histological abnormalities. Mechanistically, 6-shogaol attenuated cisplatin-induced oxidative stress and modulated the renal expression of prooxidant and antioxidant enzymes. Apoptosis and necroptosis induced by cisplatin were also suppressed by 6-shogaol. Moreover, 6-shogaol inhibited cisplatin-induced cytokine production and immune cell infiltration. These results suggest that 6-shogaol exhibits therapeutic effects against cisplatin-induced AKI via the suppression of oxidative stress, tubular cell death, and inflammation.
Highlights
Acute kidney injury (AKI) is defined as a sudden decrease in kidney function and is strongly associated with increased morbidity and mortality in hospitalized patients [1]
The administration of 6-shogaol significantly reduced the expression of both markers (Figure 3A–C). These results suggest that 6-shogaol protected mice from cisplatin-induced AKI, as represented by the amelioration of renal dysfunction and histopathological abnormalities
To explore the mechanisms underlying the protective effect of 6-shogaol on cisplatin-induced AKI, we evaluated the levels of lipid peroxidation markers 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) [19] in the kidneys
Summary
Acute kidney injury (AKI) is defined as a sudden decrease in kidney function and is strongly associated with increased morbidity and mortality in hospitalized patients [1]. Accumulating evidence suggest that AKI is significantly linked to an increased risk of chronic kidney disease [2]. Many chemotherapeutic agents have been developed for cancer patients, but their use is frequently limited by serious side effects, including nephrotoxicity [4]. Cisplatin is one of the most effective chemotherapeutic agents and is widely used in the treatment of various solid tumors, including lung, testicular, ovarian, and bladder cancers [5]. Nephrotoxicity is a major side effect of cisplatin-based therapies, with a 20–35% risk in patients receiving cisplatin, limiting the application and efficacy of cisplatin in cancer treatment [6]. Because there is no validated pharmacological treatment for cisplatininduced AKI, the development of novel medications for the renal side effect of cisplatinbased therapies is urgently needed.
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