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The Nephroprotective Effect of Tauroursodeoxycholic Acid on Ischaemia/Reperfusion‐Induced Acute Kidney Injury by Inhibiting Endoplasmic Reticulum Stress
Author(s) -
Gao Xiang,
Fu Lili,
Xiao Min,
Xu Chenggang,
Sun Lijun,
Zhang Tong,
Zheng Feng,
Mei Changlin
Publication year - 2012
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2011.00854.x
Subject(s) - tauroursodeoxycholic acid , chop , apoptosis , unfolded protein response , endoplasmic reticulum , tunicamycin , necrosis , medicine , acute tubular necrosis , acute kidney injury , kidney , pharmacology , endocrinology , chemistry , biochemistry
The incidence of acute kidney injury ( AKI ) is very high, and multiple physiopathological processes are involved, including endoplasmic reticulum stress ( ERS ). Tauroursodeoxycholic acid ( TUDCA ) is an endogenous bile acid derivative that has been reported to inhibit ERS . To determine whether TUDCA had a nephroprotective effect on AKI and to explore the exact mechanism, an ischaemia/reperfusion ( I / R )‐induced AKI mouse model and a tunicamycin‐pre‐treated TCMK ‐1 cell model were established. It was found that the renal tubular necrosis score and cell apoptosis index reached their peak 24 hr after I / R . GRP 78 and C/EBP homologous protein ( CHOP) expression and C aspase 12 activation were enhanced, reaching their peaks at 4 and 12 hr, respectively. TUDCA intervention not only decreased the renal tubular necrosis score and the cell apoptosis index but also down‐regulated GRP 78 and CHOP expression and C aspase 12 activation. The survival rate of TCMK ‐1 cells pre‐treated with TUDCA was significantly higher than that of TCMK ‐1 cells without TUDCA pre‐treatment. In conclusion, TUDCA had a nephroprotective effect on IR ‐induced AKI by inhibiting ERS and by blocking GRP 78 and CHOP expression, reducing C aspase 12 activation and inhibiting cell apoptosis.