Protective effects of Eucommia ulmoides Oliv. leaf extract on cisplatin-induced kidney injury in mice

抄録

Cisplatin is a widely used chemotherapeutic agent; however, its clinical utility is limited by dose-dependent nephrotoxicity. Although hydration and diuretics are commonly employed to mitigate renal injury, their protective efficacy remains suboptimal. Correspondingly, Eucommia ulmoides Oliv. leaf extract (ELE) is a functional food ingredient with diuretic, antioxidant, and anti-inflammatory properties. Therefore, this study investigated the protective effects of ELE against cisplatin-induced nephrotoxicity (CIN) in mice and elucidated the underlying mechanisms. Mice were administered cisplatin (15 mg/kg) with or without ELE or furosemide (potent diuretic). Cisplatin administration markedly elevated blood plasma urea nitrogen levels and reduced creatinine clearance, thereby indicating renal dysfunction. Co-administration of ELE substantially ameliorated renal function markers and attenuated histological tubular damage. In contrast, furosemide failed to improve renal dysfunction despite increasing urine output. This suggests that diuresis alone is insufficient for renal protection. Furthermore, ELE markedly suppressed cisplatin-induced upregulation of proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and renal injury markers (kidney injury molecule-1 and lipocalin-2) in kidney tissues. These findings indicate that ELE exerts renoprotective effects against CIN through diuretic, anti-inflammatory, and antioxidant mechanisms. These mechanisms most likely involve modulation of inflammatory signaling pathways in the kidneys. Overall, ELE shows promising potential as an adjunctive therapeutic agent for patients undergoing chemotherapy.