Cytotoxic Response Profiles of Cultured Renal Epithelial and Mesenchymal Cells toSelected Aromatic Hydrocarbons.
The cytotoxic responses of cultured rat renal cortico-tubular epithelial cells (TECs) and glomerular mesangial cells (GMCs) to selected polycyclic and polyhalogenated aromatic hydrocarbons (AHs) were evaluated to further define class specific differences in toxicity potential among these chemicals. Primary cultures of renal cells were exposed to benzo[a]pyrene (BaP, 0.3-30mum); naphthalene (NAPH, 1-1000mum); 2-methylnaphthalene (2-MNAPH, 1-1000mum), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 0.01-1nm); 2,3,7,8-tetrachlorodibenzofuran (TCDF, 0.05-5nm; and pentachlorophenol (PCP, 0.1-10mum for 4 or 24hr. Measurements of mitochondrial membrane fragility in TECs revealed that the polycyclic aromatic hydrocarbons (PAHs) (BaP, NAPH and 2-MNAPH) preferentially injured these cells relative to halogenated aromatic hydrocarbons (HAHs). Extended exposures to all AHs tested were associated with moderate mitochondrial injury in TECs. Challenge of TECs with AHs for 4hr did not modulate GSH levels, although modest increases in this tripeptide occurred on extended exposures. Similar response profiles were observed in GMCs, where PAHs elicited mitochondrial damage by 4hr, while extended challenge was associated with injury in response to all AHs. Only aryl hydrocarbon receptor (AhR) ligands (BaP, TCDD and TCDF) depleted intracellular glutathione (GSH) in GMCs, while extended exposures to BaP and TCDD, as well as NAPH and 2-MNAPH, were associated with rebound increases in cellular GSH content. These data indicate that AHs can compromise renal cell function by interference with mitochondrial function and GSH homeostasis and implicate both epithelial and mesenchymal populations in the nephrotoxic response to this heterogeneous class of chemicals.
Parrish
A R
AR
Department of Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA.
Alejandro
N F
NF
Bowes Iii
R C
RC
Ramos
K S
KS