Hydroxylated-Benz[a]anthracenes Induce Two Apoptosis-Related Gene Expressions in the Liver of the Nibbler Fish Girella punctata

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are known to have toxic effects on fish. In this study, we examined the effects of benz[a]anthracene (BaA), a type of PAH, on fish liver metabolism. Nibbler fish (<i>Girella punctata</i>) were intraperitoneally injected with BaA (10 ng/g body weight) four times over a 10-day period. BaA significantly decreased known bone metabolism-related plasma factors such as calcium and inorganic phosphorus. Moreover, significant reductions were observed in the plasma levels of known liver metabolism-related factors, including ferrous ions, total bile acids, total bilirubin, free bilirubin, aspartate aminotransferase, and alkaline phosphatase. Interestingly, mono-hydroxylated metabolites of BaA, such as 3 hydroxylbenz[a]anthracene (3-OHBaA), were detected in the bile of BaA-injected nibbler fish. This hydroxylated form of BaA was found in its free form, rather than conjugated with glucuronic acid or sulfuric acid. Due to the lack of whole-genome sequence data for the nibbler fish, two nibbler fish-specific apoptosis-related factors (TNF receptor superfamily member 1A: <i>tnfrsf1a</i> and TNF superfamily member 10: <i>tnfsf10</i>) were isolated by De novo RNA sequencing. In a liver tissue culture, 3-OHBaA (10^-6 M) significantly upregulated the expression of <i>tnfrsf1a</i> and <i>tnfsf10</i> in the liver. These results provide the first evidence that 3-OHBaA metabolites exhibit toxic effects on the liver in teleost.