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Original

Metallothionein over-expression in podocytes reduces adriamycin nephrotoxicity

, & , PhD
Pages 174-182 | Received 17 Jul 2008, Published online: 07 Jul 2009
 

Abstract

Adriamycin (ADR) is nephrotoxic. One component of ADR-induced nephropathy may be oxidative stress. This study used a recently developed line of transgenic mice (Nmt) on the FVB background strain, which over-express the antioxidant protein metallothionein (MT) in podocytes. Cultured podocytes from Nmt mice were resistant to H2O2 injury, as judged by disruption of F-actin filaments. FVB control and transgenic mice received 11 mg/kg body weight ADR by tail vein injection and 24-h urine samples were then collected for albumin analysis. Also renal morphology was investigated by light and electron microscopy. Urine albumin analysis showed that ADR treatment significantly increased albuminuria in control mice, indicating that the FVB strain is sensitive to ADR nephropathy and Nmt mice were significantly protected from elevated albuminuria. Glomerular histopathology revealed that ADR reduced podocyte number and produced foot process effacement in FVB mice. The Nmt transgene protected podocyte numbers and podocyte foot processes from the effects of ADR. These results show that metallothionein can protect podocytes from ADR toxicity.

Abbreviations
ADR=

Adriamycin

MT=

Metallothionein

Nmt=

Transgenic mice line that over-expresses MT in podocytes

UAE=

Urine albumin excretion

Abbreviations
ADR=

Adriamycin

MT=

Metallothionein

Nmt=

Transgenic mice line that over-expresses MT in podocytes

UAE=

Urine albumin excretion

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