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Downregulation of Glutathione Biosynthesis Contributes to Oxidative Stress and Liver Dysfunction in Acute Kidney Injury
Joint Authors
Shang, Yue
Siow, Yaw L.
Isaak, Cara K.
O, Karmin
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-10-30
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Ischemia-reperfusion is a common cause for acute kidney injury and can lead to distant organ dysfunction.
Glutathione is a major endogenous antioxidant and its depletion directly correlates to ischemia-reperfusion injury.
The liver has high capacity for producing glutathione and is a key organ in modulating local and systemic redox balance.
In the present study, we investigated the mechanism by which kidney ischemia-reperfusion led to glutathione depletion and oxidative stress.
The left kidney of Sprague-Dawley rats was subjected to 45 min ischemia followed by 6 h reperfusion.
Ischemia-reperfusion impaired kidney and liver function.
This was accompanied by a decrease in glutathione levels in the liver and plasma and increased hepatic lipid peroxidation and plasma homocysteine levels.
Ischemia-reperfusion caused a significant decrease in mRNA and protein levels of hepatic glutamate-cysteine ligase mediated through the inhibition of transcription factor Nrf2.
Ischemia-reperfusion inhibited hepatic expression of cystathionine γ-lyase, an enzyme responsible for producing cysteine (an essential precursor for glutathione synthesis) through the transsulfuration pathway.
These results suggest that inhibition of glutamate-cysteine ligase expression and downregulation of the transsulfuration pathway lead to reduced hepatic glutathione biosynthesis and elevation of plasma homocysteine levels, which, in turn, may contribute to oxidative stress and distant organ injury during renal ischemia-reperfusion.
American Psychological Association (APA)
Shang, Yue& Siow, Yaw L.& Isaak, Cara K.& O, Karmin. 2016. Downregulation of Glutathione Biosynthesis Contributes to Oxidative Stress and Liver Dysfunction in Acute Kidney Injury. Oxidative Medicine and Cellular Longevity،Vol. 2016, no. 2016, pp.1-13.
https://search.emarefa.net/detail/BIM-1114806
Modern Language Association (MLA)
Shang, Yue…[et al.]. Downregulation of Glutathione Biosynthesis Contributes to Oxidative Stress and Liver Dysfunction in Acute Kidney Injury. Oxidative Medicine and Cellular Longevity No. 2016 (2016), pp.1-13.
https://search.emarefa.net/detail/BIM-1114806
American Medical Association (AMA)
Shang, Yue& Siow, Yaw L.& Isaak, Cara K.& O, Karmin. Downregulation of Glutathione Biosynthesis Contributes to Oxidative Stress and Liver Dysfunction in Acute Kidney Injury. Oxidative Medicine and Cellular Longevity. 2016. Vol. 2016, no. 2016, pp.1-13.
https://search.emarefa.net/detail/BIM-1114806
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1114806