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Nanoparticle‐rich diesel exhaust‐induced liver damage via inhibited transactivation of peroxisome proliferator‐activated receptor alpha

Ito, Yuki, Yanagiba, Yukie, Ramdhan, Doni Hikmat, Hayashi, Yumi, Li, Yufei, Suzuki, Akira K., Kamijima, Michihiro, Nakajima, Tamie
Environmental toxicology 2016 v.31 no.12 pp. 1985-1995
air, alanine transaminase, enzyme activity, exposure duration, genes, inflammation, interleukin-6, lipid metabolism, liver, males, nanoparticles, peroxisome proliferator-activated receptors, rats, transcription factor NF-kappa B, transcriptional activation
Diesel exhaust emission contains a high amount of nano‐sized particles and is considered to be systemically distributed in the body. However, few studies about the effects of nanoparticle rich‐diesel exhaust (NR‐DE) on liver have been reported. The present investigation focuses on the effects of NR‐DE on livers in rats, especially concerning inflammation and lipid metabolism. Male F344 rats were exposed to fresh air or low (24 ± 7 µg/m³), medium (39 ± 4 µg/m³) and high (138 ± 20 µg/m³) concentrations of NR‐DE for 1, 2, or 3 months (5 hours/day, 5 days/week). Exposure to both medium and high concentrations of NR‐DE for one month increased plasma asparate aminotransferase and alanine aminotransferase activities, while only high concentrations increased plasma interleukin‐6 and hepatic nuclear factor kappa B (NFκB), suggesting that activation of hepatic inflammatory signaling took place. Although these exposures elevated peroxisome proliferator‐activated receptor (PPAR) α levels or its binding activity to the response element, neither activated PPARα‐target genes such as β‐oxidative enzymes nor inhibited NFκB elevation. Thus, NR‐DE may contain some materials that inhibit PPARα activation in relation to lipid metabolism and inflammation. Taken together, NR‐DE exposure at one month may cause inflammation; however, this finding may not be observed after a longer exposure period. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1985–1995, 2016.