Abstract
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.
Highlights
Drug-induced nephrotoxicity often occurs in long-term drug therapy[1]
Using LC–MS/MS technology, 16 trusted proteins were selected from SDAP1, and 11 trusted proteins were selected from SDAP2
The GO analysis (Fig. 4A) showed that 11 differentially expressed proteins were related to biological processes, 19 differentially expressed proteins were related to cellular components, and 17 were related to molecular functions in Sika deer antler protein (SDAPR)
Summary
Drug-induced nephrotoxicity often occurs in long-term drug therapy[1]. The nephrotoxicity is difficult to be predicted in the early stage of disease[2]. Activation of Nrf[2] can alleviate the toxicity related to reactive oxygen species and is an important molecular target for the prevention of renal injury[15] It is recorded in the Chinese pharmacopoeia that Sika deer antler (SDA) has the functions of strengthening kidney yang and enriching b lood[16]. The results of the previous studies found that Sika deer antler protects (SDAP) against acetaminophen-induced acute kidney injury by activating Nrf2/HO-1 p athway[18]. We investigated the protective effects of SDAP on HEK293 cells in GM-induced oxidative stress, inflammation and apoptosis. We hypothesized that SDAPR, SDAP1 and SDAP2 inhibit GM-induced oxidative stress, inflammatory response and apoptosis by activating the Nrf2/HO-1 pathway. Explored the mechanism of SDAP1 and SDAP2 inhibiting acute kidney injury in GM mice
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