In vitro interference with hepatocellular uptake of bile acids by xylene

Toxicology
M Neghab, N H Stacey

Abstract

Occupational exposure to a mixture of two widely used aromatic hydrocarbon solvents, xylene and toluene, has been associated with a significant rise in the concentrations of serum bile acids (SBA). We have recently shown that toluene interferes with the transport of bile acids by hepatocytes and this could explain elevated SBA after occupational exposure or following in vivo administration of this compound to experimental animals. However, it is not known if xylene, like its monomethylated homologue, toluene, could interfere with the processes of bile acid transport by hepatocytes. Therefore, the present studies were undertaken to examine this possibility. Direct addition of a non-cytotoxic dose (2.5 microliters/2.8 x 10(6) cells) of xylene (in vapour phase) to hepatocytes isolated from untreated rats significantly inhibited the initial rates (determined from slope of the lines in the linear range (20-80 s)) of uptake (V0) of 10 microM cholic acid (CA) and-taurocholic acid (TC) by 37 and 48%, respectively (P < 0.05). Similarly, accumulation of these substrates by hepatocytes over an extended incubation time up to 30 min was significantly inhibited to the same extent by xylene exposure. This inhibitory effect was found to be rev...Continue Reading

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Citations

May 2, 2002·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·L WolzU Mohr
May 29, 2004·Menopause : the Journal of the North American Menopause Society·Cornelia Bodinet, Johannes Freudenstein
May 15, 2009·Environmental Health Perspectives·Susanne BastianKristin Schirmer
Jan 1, 2000·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals· Masoud Neghab Neill H Stacey

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