Proteomic Analysis of Subchronic Furan Exposure in the Liver of Male Fischer F344 Rats

Furan is a volatile compound formed during the thermal processing of foods. Chronic exposure has been shown to cause cholangiocarcinoma and hepatocellular tumors in rodent models. We conducted a 90 day subchronic study in Fisher 344 rats exposed to various doses by gavage to determine the NOAEL. Previous reports have outlined changes in the liver using gross necropsy examination, histopathology, clinical biochemistry, hematology, immunohistochemistry, and toxicogenomics. The data revealed that males were more sensitive than females. The focus of this study was to evaluate the toxicoproteomic changes by 2-dimensional differential in gel electrophoresis followed by mass spectrometry analysis. To compliment previous studies, protein expression changes were evaluated of male animals after 90 days of exposure to doses of 0, 0.03, 0.5, and 8.0 mg/kg bw/d. Significant statistical treatment-related changes compared to the controls identified 45 protein spots containing 38 unique proteins. Proteins identified are implicated in metabolism, redox regulation, protein folding/proteolysis as well as structural and transport proteins. At lower doses, multiple cytoprotective pathways are activated to maintain a homeostasis but ultimately the loss of protein function and impairment of several pathways could lead to adverse health effects at higher doses of furan administration.