Purified Sika deer antler protein attenuates GM-induced nephrotoxicity by activating Nrf2 pathway and inhibiting NF-κB pathway

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.

Formononetin Ameliorates Renal Dysfunction, Oxidative Stress, Inflammation, and Apoptosis and Upregulates Nrf2/HO-1 Signaling in a Rat Model of Gentamicin-Induced Nephrotoxicity

“…In this study, GEN lowered Nrf2 signaling in the kidney, as proved by the suppressed Nrf2 and HO-1 levels. Consistently, several studies showed decreased Nrf2 and HO-1 levels in the renal tissue of GEN-handled animals ( He et al, 2015 ; Wang et al, 2020 ).…”

Peptide Biomarkers Discovery for Seven Species of Deer Antler Using LC-MS/MS and Label-Free Approach

“…The earliest records of medicinal use of deer antler date back 2000 years [ 3 ]. In recent years, people have studied the chemical composition, bioactive components, and pharmacological effects of deer antler [ 2 , 4 ], which has been proved to be an important nourishing and health care product with high nutritional and medicinal value; it is rich in protein [ 5 ], and has certain curative effects against breast cancer [ 6 ], prostate cancer [ 7 ], acute kidney injury [ 8 ], physical decline [ 9 ], sexual dysfunction [ 10 ], neuronal damage [ 11 ], cardiac fibrosis [ 12 ], ischemic heart disease [ 13 ], vascular disease [ 14 ], osteoporosis [ 9 ], hepatocyte injury [ 15 ], and so on. Deer antler is also the raw material of deer horn gelatin [ 16 ], which has been proven to improve blood circulation.…”

Neurotherapeutic Potential of Cervus elaphus Sibericus on Axon Regeneration and Growth Cone Reformation after H2O2-Induced Injury in Rat Primary Cortical Neurons

“…Furthermore, CES has shown antioxidant effects in murine models of obesity, rheumatoid arthritis, fatty liver, and nephrotoxicity [ 11 , 20 , 21 , 22 ], and previous studies, particularly those focusing on neurological disease, have reported that the methanol extracts of velvet antler ameliorate Parkinson’s disease by inhibiting oxidative stress and neuroinflammation [ 18 ]. Although these results were demonstrated in neuronal-like cell lines and various disease models, neurotherapeutic effects have not been directly observed in mature neurons.…”