Diosmetin Relieves Cisplatin-induced Acute Kidney Injury Through The Nrf2 Antioxidant Signaling Pathway

Acute kidney injury(AKI)is a clinical syndrome caused by a variety of causes that greatly traumatizes renal function,and is also one of the most common serious diseases in the clinic.The medical expenses required for the treatment of AKI are high,and there is currently no effective treatment and preventive measures.A large number of studies have reported that one of the important causes of AKI is drug-induced kidney injury,especially antitumor drugs and antibiotic drugs have significant side effects on kidney tissue,and in the clinical diagnosis process,cisplatin is causing drug-induced kidney damage The proportion in is the largest.Clinical investigations have shown that due to the dose-dependent acute renal toxicity of cisplatin,the incidence of renal damage of cisplatin in clinical chemotherapy is 25% to 35%,which greatly limits its clinical application.As a natural flavonoid compound,diosmetin has rich pharmacological activity.In this experiment,taking mouse renal tubular epithelial cells(m RTEC)as the cell model and C57BL/6 mice as the animal model,it is shown that acute kidney injury caused by cisplatin can be alleviated by diosmetin.In this experiment,cisplatin was used to construct two models in vitro and in vivo with m RTEC cells and C57 BL / 6 mice,respectively,to explore the protective effect and mechanism of diosmetin on cisplatin-induced AKI in vivo and in vitro.In m RTEC cells,we used cisplatininduced m RTEC cells to study the antioxidant,anti-inflammatory and anti-apoptotic effects of diosmetin in cells.In this process,we mainly applied MTT method,flow cytometry,Hoehcst / PI staining method and immunoblotting method.In C57BL/6 mice,we injected cisplatin into mice to construct an AKI model,and tested the protective effect and mechanism of diosmetin in the cisplatin-induced AKI mouse model.The experimental results showed that in vitro,diosmetin significantly reduced the ROS level in cisplatin-induced m RTEC cells,and detection of apoptosisrelated results showed that it had a good protective effect on cells.At the same time,diosmetin activated the Nrf2 antioxidant signaling pathway,reduced the inflammation-related MAPK signaling pathway and reduced the occurrence of apoptosis.In vivo,diosmetin could significantly reduce kidney damage caused by cisplatin.This result could be obtained by detecting urea nitrogen(BUN)and serum creatinine(SCr)in the blood.In addition,diosmetin could reduce the oxidation index caused by cisplatin,the reduction of SOD and GSH content in the body,and the increase of MDA and MPO content have been corrected.In addition,through histopathological analysis of the kidney,compared with the cisplatin group,diosmetin significantly reduced kidney damage caused by cisplatin.Western blot results of kidney tissue showed that diosmetin activated Nrf2 in a dosedependent manner,weakened the MAPK anti-inflammatory signaling pathway,and inhibited the expression of apoptotic proteins,thereby protecting the kidney from acute kidney injury caused by cisplatin.In summary,diosmetin can protect the body from acute kidney injury induced by cisplatin through the Nrf2 antioxidant signaling pathway.Therefore,diosmetin has great potential in the application of anti-toxic side effects of drugs,and can also provide a basis for strengthening cisplatin anti-tumor treatment and protect human health.