Date on Master's Thesis/Doctoral Dissertation


Document Type

Doctoral Dissertation

Degree Name

Ph. D.


Pharmacology and Toxicology

Committee Chair

Epstein, Paul N.

Author's Keywords

Diabetic nephropathy; Adriamycin; Renal gene expression; Podocyte; Albuminuria; Metallothionein


Diabetic nephropathies; Oxidative stress


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.