Although gentamicin is widely used as an antibiotic in clinical practice, it also has some side-effects, such as acute kidney injury, which is a common condition caused by the abuse of gentamicin. Sika deer antler protein (SDAPR) can antagonize drug-induced AKI. Since SDAPR is recognized as an effective part of velvet antler, its components were further separated. Two components named SDAP1 and SDAP2 were obtained. The protective effects of SDAPR, SDAP1 and SDAP2 on GM-induced cytotoxicity to HEK293 and its potential mechanisms were studied. MTT and xCELLigence Real-Time cell analysis showed that SDAPR, SDAP1 and SDAP2 could protect HEK293 cells from GM toxicity. Similarly, SDAPR, SDAP1 and SDAP2 can reduce ROS level, reduce oxidative stress and improve inflammation Further studies have shown that SDAPR, SDAP1 and SDAP2 upregulate the Nrf2/HO-1 pathway by increasing the expression of Nrf2 and HO-1, and down-regulate the NF-κB pathway by reducing the protein expression of NF-κB. Annexin V/PI flow cytometry and Hoechst 33258 staining showed that SDAPR, SDAP1 and SDAP2 inhibited GM-induced apoptosis in HEK293 cells. Western blot analysis showed SDAPR, SDAP1 and SDAP2 decreased expression level of Bax and Cleaved-caspase-3, and increased the expression level of Bcl-2. In addition, we examined the feasibility of SDAP1 and SDAP1 to avoid kidney injury in a GM mouse model. In conclusion, SDAPR, SDAP1 and SDAP2 can be used to prevent GM-induced HEK293 cytotoxicity, probably because they have strong anti-oxidative stress, anti-inflammatory and anti-apoptotic effects. And SDAP1 and SDAP2 can inhibit GM-induced acute kidney injury in mice.
The cellular defense pathway plays a key role in maintaining the homeostasis, tissues and organisms. Nuclear factor E2-related factor 2 (Nrf2), as a key cell signaling pathway, plays an important role in encoding detoxification enzymes and other stress response mediators. Recent studies have shown that it is closely related to the prevention and treatment of acute kidney injury (AKI). Therefore, this article reviews the protective effects of Nrf2-related signaling pathways on acute kidney injury, and summarizes the strategies of natural pharmaceutical ingredients such as flavonoids, alkaloids, terpenes, phenylpropionic acid, polyphenols, and polysaccharides to prevent and treat acute kidney injury. It is of great significance to further study the relationship between Nrf2 regulated signal pathway and kidney disease and the development of new medicines for acute kidney injury treatment. It can also provide new ideas and treatment strategies for clinical treatment of acute kidney injury. Practical applications This article reviewed the mechanisms by which the active ingredients of natural medicines slow down acute kidney injury through the Nrf2 pathway. It will help us to understand the regulatory role of the Nrf2 pathway in AKI more comprehensively, and provide a theoretical basis for further exploring the mechanism of more natural drugs to reduce acute kidney injury.
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