Study on potential antioxidant activity of Fisetin against oxidative stress in vivo
Loading...
Date
2018
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
DEPARTMENT OF MOLECULAR AND CELLULAR ENGINEERING SAM HIGGINBOTTOM UNIVERSITY OF AGRICULTURE AND TECHNOLOGY SCIENCES (FORMERLY ALLAHABAD AGRICULTURE INSTITUTE) ALLAHABAD -211007, INDIA 2018
Abstract
Oxidative stress is common mechanism that is implicated in the progression of various diseases.
Oxidative stress is mainly induced by ROS. Relatively increased level of ROS damages the
biomolecules such as DNA, protein and lipid. Lipid peroxidation is common damage induced by
ROS thus preferably used as indicator for oxidative stress in research. Cell and mitochondria
have antioxidant system to keep the ROS level under control. Altered activity of antioxidant
enzymes and glutathione level causes oxidative stress .There are two established situations that
are cause of oxidative stress. First, transcriptional suppression of expression of antioxidant
enzymes and second is altered activity of antioxidant enzymes due to toxicity. Fisetin, a dietary
flavonoid, has shown several chemopreventive effects against various ROS leads to disease.
Structural evidences and in vitro studies suggested the antioxidant potential of fisetin. However,
in vivo studies are largely less explored to suggest the mechanism of action in mitochondria and
transcriptional suppression model. Thus, present study was conducted on above two situations to
evaluate antioxidant potential of fisetin against oxidative stress in vivo. For First situation, CoCl2
induced cerebral cortex hypoxia model (40 mg/Kg body wt. for 15 days) was used which showed
HIF mediated transcriptional suppression of SOD and CAT. Second, cisplatin (6mg/Kg body wt
single dose) toxicity induced altered activity of antioxidant enzymes. In both the situations GSH
level was also studied. In first situation, fisetin could able to prevent the transcriptional
suppression mediated depletion of activity of SOD and CAT. Glutathione peroxidase activity
was also enhanced by fisetin. In addition fisetin could able to increase the synthesis of GSH in
fisetin alone group and similar increased level of GSH was observed in combined group also. In
second situation, fisetin could able to restore the SOD, CAT, GPx and GR. In addition, fisetin
I
could able to restore the GSH level in mitochondrial matrix. Thus, in both the situations fisetin
could able to modulate the antioxidant enzymes activity and restore GSH level in consequence
reduced the level of ROS and LPO. However, further study is needed to confirm whether and
how fisetin alter the HIF1α mediated transcription in cytosol and transport of GSH to
mitochondria.
Description
Ph. D. Thesis
Keywords
null