Renal and hepatic accumulation of cadmium and lead in the expression of CYP4F2 and CYP2E1

Baker, JR, Edwards, RJ, Lasker, JM, Moore, MR and Satarug, S (2005) Renal and hepatic accumulation of cadmium and lead in the expression of CYP4F2 and CYP2E1. Toxicology Letters, 159 2: 182-191. doi:10.1016/j.toxlet.2005.05.016


Author Baker, JR
Edwards, RJ
Lasker, JM
Moore, MR
Satarug, S
Title Renal and hepatic accumulation of cadmium and lead in the expression of CYP4F2 and CYP2E1
Journal name Toxicology Letters   Check publisher's open access policy
ISSN 0378-4274
Publication date 2005
Sub-type Article (original research)
DOI 10.1016/j.toxlet.2005.05.016
Volume 159
Issue 2
Start page 182
End page 191
Total pages 10
Editor J. Kehrer
W. Dekant
Place of publication Clare
Publisher Elsevier Ireland Ltd
Collection year 2005
Language eng
Subject C1
321299 Public Health and Health Services not elsewhere classified
730210 Environmental health
Abstract The present study examined accumulation of the metal toxins cadmium (Cd) and lead (Pb) in relation to the abundance of cytochrome P450 4F2 (CYP4F2), CYP2E1 and concentrations of zinc and copper in liver and kidney samples using immunoblotting coupled with metal analysis. The post mortem liver and kidney cortex samples were from 23 males and 8 females aged 3-89 years. All were Caucasians who had not been exposed to metals in the workplace. Average kidney cortex Cd load of 17.4 mu g/g w.w. was 17 times greater than average liver Cd load (1.1 mu g/g w.w.). In contrast, average kidney cortex Ph load of 0.09 mu g/g w.w. was two times lower than liver Pb load of 0.19 mu g/g w.w. Average Zn and Cu concentrations in the kidney cortex samples were 67% and 33% lower than those in the liver. Liver and kidney Cd loads, but not liver or kidney Ph loads, correlated positively with donors' age. After controlling for liver Cd load, an inverse correlation was seen between Zn and age (partial r = -0.39, P = 0.02), suggesting reduction in liver Zn levels in old age. Liver CYP2E1 protein abundance correlated with age-adjusted Cd load (partial r = 0.37, P = 0.02) whereas kidney CYP4172 protein abundance showed a positive correlation with age-adjusted Cd loads (partial r = 0.40, P = 0.02). These findings suggest that Cd may be an inducer of renal CYP4172 and hepatic CYP2E1 and that increased renal CYP4172 expression may implicate in Cd-linked renal tubular dysfunction and high blood pressure, involving CYP4F2-dependent arachidonic acid metabolism. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
Keyword Toxicology
Metal Toxins
Cadmium
Lead
Zinc
Copper
Environmental Exposure
Cyp2e1
Cyp4f2
Human Liver
Human Kidney
Low-level Cadmium
20-hydroxyeicosatetraenoic Acid
Arachidonic-acid
Blood-pressure
Environmental Cadmium
Function Biomarkers
Oxidative Stress
Kidney Cortex
Bone Lead
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 05:46:15 EST