Study On Hepatotoxicity And Neurotoxicity Induced By TBBPA Novel Derivative BADPP In Rats

Brominated flame retardants such as tetrabromobisphenol-A(TBBPA) may exert environmental toxicity and increase the risk to human health. The objective of this study is to evalate the possible hepatotoxicity of 2, 2-Bis(4-allyloxy-3, 5-dibromophenyl)propane(BADPP), a TBBPA derivative, in rats.24 Adult male Sprague Dawley rats were divided randomly into three groups:high-dose group, low-dose group, and control group. BADPP was dissolved in peanut oil and orally administered once a day for 28 consecutive days at the doses of 500mg/kg,100mg/kg, and 0, respectively. After the rats were sacrificed, the blood samples, livers tissue and hippocampuswere collected. The hepatic injury were assessed by both histological and biochemical observations. And the neurotoxicity were studied by means of behavior and differential proteomics.The study of hepatotoxicity demonstrate that long-term exposed to 2, 2-Bis(4-allyloxy-3, 5-dibromophenyl) propane not only significantly increased the serum levels of aspartate aminotransferase, alanine aminotransferase and albumin, but increased in relative liver weight of rats. The histopathological evidences showed that the test compound induced the hepatotoxicity such as mild hypertrophy, steatosisand vacuolation of hepatocytes. This maybe induced by the elevated oxidative stress in liver and the upregulation of SSAO in liver microsome.In the neurotoxicity study, both the Morris water maze and the novel object recognition test showed that 2,2-(4- allyloxy-3,5- dibromophenyl) propane have an effect on the learning and memory of rats. Moreover, 18 O labeling quantitative proteomics were applied to investigate the differences in protein expessin of hippocampal memebrane.Finally, 28 different proteins were obtained, including 23 down-regulated proteins and 5up-regulated proteins. Classification of these differential proteins can be found to be divided into 9 groups, 6 structural proteins(21.4%), 9 regulatory proteins(32.1%), 6transporter proteins(21.4%), one energy metabolism related proteins(3.6%), one carbohydrate metabolism related protein(3.6%), one amino acid metabolism related protein(3.6%), one nucleotide metabolism associated proteins(3.6%) and one proteasome(3.6%). One protein(3.6%) function is unknown. The neurotransmitters related proteins,including Clathrin heavy chain, FXYD domain-containing ion transport regulator 6, 78 kDa glucose-regulated protein, Voltage-dependent anion-selective channel protein and Amine oxidase [flavin-containing], were downregulated which indicated BADPP could affect the ability of learning and memory in the hippocampus by regulating the Protein expression associated with the process of synaptic transmission.Hence, we conclude that the 2, 2-Bis(4-allyloxy-3, 5-dibromophenyl) propane could induced liver injuries and neurotoxicity.