Influence of ethylbenzene on the levels of mandelic acid and phenylglyoxylic acid in urine, ultrastructure and the expressions of Mitochondrial apoptotic-related proteins in the rat nephridial tissues / 中华劳动卫生职业病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the influence of ethylbenzene on the levels of mandelic acid (MA) and phenylglyoxylic acid (PGA) in urine, the ultrastructure and the expressions of mitochondrial apoptotic-related genes in the rat nephridial tissues.</p><p><b>METHODS</b>Four groups of 10 males of Sprague-Dawley rats were allocated randomly into four groups control (C) group, low (L) group, moderate (M) group and high (H) group, and inhaled daily with different doses of ethylbenzene 0, 433.5 mg/m(3), 4335 mg/m(3), and 6500 mg/m(3) 6 h per day, 5 days per week for 13 weeks. The mandelic acid and phenylglyoxylic acid in the urine was assayed by high performance liquid chromatography. The ultrastructure of nephridial tissue was observed via electron microscope. The protein expression levels of Bax, Bcl-2, cytochrome C, Caspase-9 and Caspase-3 in nephridial tissues were measured by Western blot, respectively.</p><p><b>RESULTS</b>The levels of MA [(0.303 +/- 0.148) mg/L, (0.404 +/- 0.154) mg/L] and PGA [(0.168 +/- 0.104) mg/L, (0.174 +/- 0.092) mg/L] in the urine of M and H groups were significantly higher than that in the control and L group [(0.084 +/- 0.070) mg/L, (0.041 +/- 0.029) mg/L] (P < 0.05, respectively). It has been shown a dose-effect relationship between the contents of MA, PGA and MA + PGA and inhaled ethylbenzene, respectively. The mitochondria of rat nephridial tissue of H group became a compact and vacuolar structure with disorder and loss of cristae. The expression levels of Bax in mitochondria of nephridial tissues of M and H groups were significantly lower than that in the control group (P < 0.05). Caspase-3 expression level in H group was remarkably higher than that in the control group (P < 0.05). Compared with the control group, the expression levels of cytochrome C and Caspase-9 were enhanced, while the expression levels of Bcl-2 were restrained in all ethylbenzene-treated groups (P < 0.05, P < 0.05, respectively). The expression levels of Caspase-3 in M and H groups were significantly higher than that in the control group and L group (P < 0.05).</p><p><b>CONCLUSION</b>Ethylbenzene can induce apoptosis in the cells of nephridial tissues. The apoptotic mechanism might be involved with up-regulation of Bax, cytochrome C, Caspase-9 and Caspase-3, as well as restraint of Bcl-2. The level of MA and PGA in the rat urine could be a parameter of biological dose in vivo after ethylbenzene inhalation.</p>