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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 Front+Pharmacol
2018 ; 9
(ä): 638
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Mangiferin Ameliorates Cisplatin Induced Acute Kidney Injury by Upregulating
Nrf-2 via the Activation of PI3K and Exhibits Synergistic Anticancer Activity
With Cisplatin
#MMPMID29967581
Sadhukhan P
; Saha S
; Dutta S
; Sil PC
Front Pharmacol
2018[]; 9
(ä): 638
PMID29967581
show ga
Occurrence of oxidative stress is the principal cause of acute kidney injury
induced by cisplatin. Mangiferin, a naturally occurring antioxidant molecule, is
found to ameliorate several oxidative stress mediated pathophysiological
conditions including cancer. Cisplatin induced cytotoxicity was measured in NKE
cells by MTT assay and microscopic analysis. Induction of oxidative stress and
regulation of proapoptotic molecules were subsequently investigated by using
different spectrophotometric analyses, FACS and immunocytochemistry. Induction of
nephrotoxicity was determined by analyzing different serum biomarkers and
histological parameters in vivo using swiss albino mice. Activation of NF-?B
mediated pro-inflammatory and caspase dependent signaling cascades were
investigated by semi-quantitative RT-PCR and immunoblotting. Mangiferin was found
to ameliorate cisplatin induced nephrotoxicity in vitro and in vivo by
attenuating the induction of oxidative stress and upregulating Nrf-2 mediated
pro-survival signaling cascades via the activation of PI3K. Additionally,
mangiferin showed synergistic anticancer activity with cisplatin in cancer cell
lines (MCF-7 and SKRC-45) and EAC cell induced solid tumor bearing experimental
mice. The ameliorative effect of mangiferin is primarily attributed to its
anti-oxidant and anti-inflammatory properties. It acts differentially in normal
tissue cells and tumor cells by modulating different cell survival regulatory
signaling molecules. For the first time, the study reveals a mechanistic basis of
mangiferin action against cisplatin induced nephrotoxicity. Since Mangiferin
shows synergistic anticancer activity with cisplatin, it can be considered as a
promising drug candidate, to be used in combination with cisplatin.