Adriamycin nephrotoxicity is reduced by metallothionein over-expression and kidney gene expression is modified by diabetes in the OVE26 diabetic model.

by Lu Yang

Institution: University of Louisville
Department: Department of Pharmacology and Toxicology
Degree: PhD
Year: 2010
Keywords: Diabetic nephropathy; Adriamycin; Renal gene expression; Podocyte; Albuminuria; Metallothionein
Record ID: 1866087
Full text PDF: http://ir.library.louisville.edu/etd/1618


This thesis is divided into two parts below. Part I Adriamycin (ADR) can produce nephrotoxicity in rodents. The underlying mechanism may relate to ADR induced oxidative stress. In this study, we used transgenic mice (NMT3), which over-expressed the antioxidant protein metallothionein (MT) in podocytes, to study MT's protective potential on ADR nephrotoxicity. Urine and kidney samples were collected from control and transgenic mice at multiple time points after ADR injection, whose results showed that MT transgene alleviated ADR damage by reducing albuminuria, decreasing podocyte loss and protecting podocyte ultra-structure. Part II OVE26 mice are a good model of severe diabetic nephropathy (DN). We examined progressive changes in renal gene and protein expression in OVE26 and control mice. Inflammatory genes were most affected by diabetes, especially at oldest ages tested, which correlated with increasingly severe albuminuria. Vitamin D metabolism was also changed by DN.