Commercial naphthenic acids and the organic fraction of oil sands process water induce different effects on pro-inflammatory gene expression and macrophage phagocytosis in mice

• Published in: Journal of applied toxicology 2012-12, Vol.32 (12), p.968-979
• Main Authors: Garcia-Garcia, Erick, Pun, Jonathan, Hodgkinson, Jordan, Perez-Estrada, Leonidas A., El-Din, Mohamed Gamal, Smith, Daniel W., Martin, Jonathan W., Belosevic, Miodrag
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Carboxylic Acids - toxicity; Cells, Cultured; Cellular biology; Cytokines - genetics; Down-Regulation; Exposure; Female; Flow Cytometry; Gene expression; Gene Expression - drug effects; immunotoxicity; inflammation; innate immunity; Liver - drug effects; Liver - metabolism; Lymph Nodes - drug effects; Lymph Nodes - metabolism; Macrophages; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - immunology; Medical sciences; Mice; Mice, Inbred C57BL; Mining; Naphthenic acids; Oil sands; oil sands process water; OSPW; Petroleum; Phagocytosis; Phagocytosis - drug effects; Real-Time Polymerase Chain Reaction; Silicon Dioxide - chemistry; Spleen - drug effects; Spleen - metabolism; Time Factors; Toxicity; Toxicology; Up-Regulation; Waste Water - toxicity
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.1687

ABSTRACT Naphthenic acids (NAs) are believed to be the major toxic component of oil sands process water (OSPW). Different OSPW preparations have distinct NA compositions, and additional organics, that differ from the commercial NAs (C‐NAs) often used for toxicology studies. To evaluate whether C‐NAs are an adequate model to study OSPW toxicity in complex organisms, we compared the effects of C‐NAs and the extractable organic fraction of OSPW (OSPW‐OF) on mice immune mechanisms. Mice were orally exposed to different C‐NA doses, or OSPW‐OF at the same NA dose, for up to 8 weeks, and the expression of pro‐inflammatory genes in different organs was determined using quantitative PCR. C‐NAs and OSPW‐OF altered the expression of pro‐inflammatory genes, inducing either expression down‐regulation or up‐regulation, depending on the organ examined and time after exposure. The time at which gene expression alterations occurred, and the specific sets of genes whose expression was altered, were very different between animals exposed to C‐NAs or to OSPW‐OF. We evaluated the ability of mouse peritoneal macrophages to phagocytose yeast cell wall, as a measure of the ability of mice to mount a central function of the innate immune response. Phagocytosis was significantly reduced in animals exposed to C‐NAs, but enhanced in mice exposed to OSPW‐OF. Our results indicate that studies using C‐NAs may not necessarily reflect the possible effects induced in animals by process water from tailing ponds. Copyright © 2011 John Wiley & Sons, Ltd. Naphthenic acids (NAs) are believed to be the major toxic component of oil sands process water (OSPW). We evaluated whether commercial NAs are an adequate model to study OSPW toxicity in complex organisms. We compared the effects of commercial NAs preparation and the organic fraction of OSPW by measuring the pro‐inflammatory gene expression and macrophage phagocytosis, and found that commercial NAs and OSPW induce different biological effects in mice.