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2017 ; 8
(ä): 178
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Activation of Sirtuin 3 by Silybin Attenuates Mitochondrial Dysfunction in
Cisplatin-induced Acute Kidney Injury
#MMPMID28424621
Li Y
; Ye Z
; Lai W
; Rao J
; Huang W
; Zhang X
; Yao Z
; Lou T
Front Pharmacol
2017[]; 8
(ä): 178
PMID28424621
show ga
Silybin is a secondary metabolite isolated from the seeds of blessed milk thistle
(Silybum marianum) that has anti-inflammatory, antioxidative, antifibrotic, and
antitumor properties. Here, we showed that silybin protected against
cisplatin-induced acute kidney injury (AKI) by improving mitochondrial function
through the regulation of sirtuin 3 (SIRT3) expression. Male SV129 and SIRT3
knockout (KO) mice were administered a single intraperitoneal (i.p.) injection of
cisplatin with or without treatment with silybin. Moreover, cultured HK2 cells
were used to evaluate mitochondrial morphology and function. Our data suggested
that silybin enhanced SIRT3 expression after cisplatin administration both in
vivo and in vitro. Silybin treatment improved mitochondrial function and
bioenergetics in wild-type, but not SIRT3-defective, cells and mice. Moreover, we
demonstrated that silybin markedly attenuated cisplatin-induced AKI and tubular
cell apoptosis and improved cell regeneration in a SIRT3-dependent manner.
Collectively, these results suggest that silybin is a pharmacological activator
of SIRT3 capable of protecting against cisplatin-induced tubular cell apoptosis
and AKI by improving mitochondrial function. Thus, silybin could serve as a
potential clinical renoprotective adjuvant treatment in cisplatin chemotherapy.