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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Acta+Pharmacol+Sin
2016 ; 37
(2
): 235-45
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Emodin ameliorates cisplatin-induced apoptosis of rat renal tubular cells in
vitro by activating autophagy
#MMPMID26775661
Liu H
; Gu LB
; Tu Y
; Hu H
; Huang YR
; Sun W
Acta Pharmacol Sin
2016[Feb]; 37
(2
): 235-45
PMID26775661
show ga
AIM: A previous report shows that emodin extracted from the Chinese herbs rhubarb
and giant knotweed rhizome can ameliorate the anticancer drug cisplatin-induced
injury of HEK293 cells. In this study, we investigated whether and how emodin
could protect renal tubular epithelial cells against cisplatin-induced
nephrotoxicity in vitro. METHODS: The viability and apoptosis of normal rat renal
tubular epithelial cells (NRK-52E) were detected using formazan assay and flow
cytometry analysis, respectively. The expression levels of cleaved caspase-3,
autophagy maker LC3 I/II, and AMPK/mTOR signaling pathway-related proteins were
measured with Western blot analysis. The changes of morphology and RFP-LC3
fluorescence were observed under microscopy. RESULTS: Cisplatin (10-50 ?mol/L)
dose-dependently induced cell damage and apoptosis in NRK-52E cells, whereas
emodin (10 and 100 ?mol/L) significantly ameliorated cisplatin-induced cell
damage, apoptosis and caspase-3 cleavage. Emodin dose-dependently increased
LC3-II levels and induced RFP-LC3-containing punctate structures in NRK-52E
cells. Furthermore, the protective effects of emodin were abolished by
bafilomycin A1 (10 nmol/L), and mimicked by rapamycin (100 nmol/L). Moreover,
emodin increased the phosphorylation of AMPK and suppressed the phosphorylation
of mTOR. The AMPK inhibitor compound C (10 ?mol/L) not only abolished
emodin-induced autophagy activation, but also emodin-induced anti-apoptotic
effects. CONCLUSION: Emodin ameliorates cisplatin-induced apoptosis of rat renal
tubular cells in vitro through modulating the AMPK/mTOR signaling pathways and
activating autophagy. Emodin may have therapeutic potential for the prevention of
cisplatin-induced nephrotoxicity.