Show simple item record

dc.contributor.supervisor O, Karmin (Animal Science) en_US
dc.contributor.author Shang, Yue
dc.date.accessioned 2018-09-11T15:51:54Z
dc.date.available 2018-09-11T15:51:54Z
dc.date.issued 2018-08 en_US
dc.date.submitted 2018-08-29T19:12:07Z en
dc.identifier.citation Shang Y., Y. L. Siow, C. K. Isaak and K. O. 2016. Downregulation of glutathione biosynthesis contributes to oxidative stress and liver dysfunction in acute kidney injury. Oxidative Medicine and Cellular Longevity, 2016(10):1-13. en_US
dc.identifier.uri http://hdl.handle.net/1993/33298
dc.description.abstract Ischemia-reperfusion (IR) is a major cause of acute kidney injury (AKI). AKI is often associated with dysfunction of remote organs also known as distant organ injury. Previous clinical and animal studies have identified that oxidative stress and inflammation are main pathological components in renal IR injury. However, their roles and regulatory mechanisms in distant organs are not well understood. Liver is a key metabolic organ for redox balance, immune regulation and detoxification. Liver function is often compromised by AKI. The general objective of my research was to investigate the mechanism by which renal ischemia-reperfusion led to oxidative stress and inflammatory responses in the liver. The left kidney of Sprague-Dawley rats was subjected to 45min ischemia followed by 1h or 6h of reperfusion. Renal ischemia-reperfusion impaired kidney and liver function as indicated by increased plasma creatinine and aminotransferase levels. A decrease in glutathione level was observed in the liver and plasma, along with increased hepatic lipid peroxidation and plasma homocysteine levels, as indicators of oxidative stress. Renal ischemia-reperfusion caused a significant decrease in mRNA and protein levels of hepatic enzyme cystathionine gamma-lyase, which regulates the transsulfuration pathway. A decrease in gene expression of glutamate-cysteine ligase subunits for glutathione biosynthesis was mediated through inhibition of the transcription factor Nrf2. Renal IR also caused a significant increase in proinflammatory cytokine (MCP-1, TNF-α, IL-1beta and IL-6) protein levels in the liver, kidney and plasma. Activation of nuclear transcription factor kappa B (NF-kappaB) was detected in the liver at 1h and 6h after renal IR. This was accompanied with a significant increase in the mRNA levels of proinflammatory cytokines in the liver. An elevation of myeloperoxidase activity and inflammatory foci were detected in the liver at 6h after renal IR, indicating neutrophil infiltration. In conclusion, results from our research have demonstrated that renal IR can induce acute liver injury. We have identified that during renal IR, down-regulation of hepatic Nrf2/glutathione production and up-regulation of NF-kappaB/cytokine expression are responsible for increased oxidative stress and inflammatory response, which, in turn, exert detrimental effects to distant organs. en_US
dc.rights info:eu-repo/semantics/openAccess
dc.subject Acute kidney injury en_US
dc.subject Renal ischemia-reperfusion en_US
dc.subject Distant organ injury en_US
dc.subject Oxidative stress en_US
dc.subject Inflammation en_US
dc.subject Glutathione synthesis en_US
dc.title Investigation of renal ischemia-reperfusion induced liver injury en_US
dc.type info:eu-repo/semantics/doctoralThesis
dc.type doctoral thesis en_US
dc.degree.discipline Animal Science en_US
dc.contributor.examiningcommittee House, James (Food and Human Nutritional Science), Pierce, Grant (Physiology and Pathophysiology), Leung, Susan (Department of Pharmacology and Pharmacy, The University of Hong Kong) en_US
dc.degree.level Doctor of Philosophy (Ph.D.) en_US
dc.description.note October 2018 en_US


Files in this item

This item appears in the following Collection(s)

Show simple item record

View Statistics