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Sika deer antler protein against acetaminophen-induced nephrotoxicity by activating Nrf2 and inhibition FoxO1 via PI3K/Akt signaling.

Abstract：

:Acetaminophen (APAP)-induced acute kidney injury (AKI) has turned into a typical reason for clinic obtained renal disappointment. In any case, the advancement of prophylaxis procedures and endorsed treatments for APAP-AKI is restricted. Sika deer antler protein (SDAPR) has a protective effect on drug-induced AKI. The reason for this investigation was to clarify the material premise and atomic instrument of the defensive impact of SDAPR on APAP-induced AKI. We conducted column chromatography on SDAPR extracted with Sephadex G-100 and obtained proteins of 2 different components named sika deer antler protein 1 (SDAP1) and sika deer antler protein 2 (SDAP2), respectively. MTT assay and xCELLigence Real-Time Cell Analysis showed that SDAPR, SDAP1 and SDAP2 had protective effects on APAP-induced cytotoxicity in Human kidney tubular epithelial (HK-2) cells. Therefore, we conducted proteomic analysis on SDAPR, SDAP1 and SDAP2. What's more, we inspected them viability of avoiding renal damage in APAP mice and HK-2 cells model. Contrasted and saline, SDAPR, SDAP1 and SDAP2 pretreatment portion conditionally fundamentally constricted heights in kidney damage Markers and the histological changes of renal cylindrical wounds, diminished the quantity of apoptosis-positive rounded cells, initiated NF-E2 p45-related factor 2 (Nrf2), inhibition Forkhead box O 1 transcription factors (FoxO1) and brought down the degrees of renal oxidative stress and apoptosis prompted by APAP. The above security of SDAPR, SDAP1 and SDAP2 was nullified by the Phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) in HK-2 cells. In this manner, our outcomes exhibit that, SDAPR, SDAP1 and SDAP2 against APAP-induced oxidative stress and apoptosis by initiating Nrf2 and restraint FoxO1 through PI3K/Akt signaling.

journal_name

Int J Biol Macromol

journal_title

International journal of biological macromolecules

authors

Ruan H,Luo J,Wang L,Wang J,Wang Z,Zhang J

doi

10.1016/j.ijbiomac.2019.08.164

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

961-987

eissn

0141-8130

issn

1879-0003

pii

S0141-8130(19)35499-6

journal_volume

141

pub_type

杂志文章

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Sika deer antler protein against acetaminophen-induced nephrotoxicity by activating Nrf2 and inhibition FoxO1 via PI3K/Akt signaling.