Metallothionein over-expression in podocytes reduces adriamycin nephrotoxicity.
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 H(2)O(2) 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.
Yang
Lu
L
Department of Pharmacology and Toxicology, University of Louisville, KY, USA.
Zheng
Shirong
S
Epstein
Paul N
PN
D000818:Animals; D004317:Doxorubicin / Q000633:toxicity*; D015870:Gene Expression; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D008668:Metallothionein / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D004317:Doxorubicin; D008668:Metallothionein