The Toxic Effects Of Arsenic On The Expression Of Liver Membrane Transport Protein (Multidrug Resistance-Associated Protein 2) In Rats

Objective To observe arsenic toxic effects on rat's liver and investigate the role of canalicular multispeciilc organic anion transporter/mul tiding resistance-associated protein 2 (cMOAT/MRP2) in the bile secretion of arsenic.Method Firstly, acute toxicity was conducted by oral administration using Horn's method to get half lethal dose (LD50). Secondly, thirty healthy rats were divided randomly into six groups based on time interval in dose of 20 nig/kg: 2 w . 4w , 6 w and their counterparts ofcontrol groups. They were administered every other day. Arsenic inblood and bile were detected by atomic absorption spectroscopy (AAS). and using Western blotting the expression of MRP2 in the membrane of hepatocyte was determined. By light microscopy and eletric microscopy, the morphological changes were observed. Thirdly, six biochemical indexes: Alanine aminotransferase (ALT) , sulfhydryl groups (SH). total bilirubin in serum, sialic acid (SA), glutathioneperoxidase (GSII-PX). and malonic acid (MDA) were selected to show the toxic effects on rats.Results The LD50 of arsenite is 43 mg/kg. Total arsenic levels in blood and bile were significantly higher than control groups (P<0.05) at all three different time points. The upexpression of MRP2 was 36. 61% , 152. 36% , 1 2.73% respectively ranging from 2 \v to 6 w ( percentage of controls . P<0.05 ). The quantity of MRP2 correlated with total arsenic in bile. There was prolilerative and necrosis signs in morphology by light microscopy. In bile canaliculi microvilli became swelling and sparse. At the same time, the shape of nuclear showed irregular and some of milochondrial cristae missed or broken by electric microscopy compared with control groups. ALT in serum was only affected at 6 w and markedly raised. Total bilirubin in serum was increased at 4w and 6vv time points. S1I in serum was found almost unresponsive to arsenic. MDA in serum and GS11-PX in blood were increased (P<0.05). except 2w. The results of SA in serum remained unchanged between experimental groups and control groups.Conclusion Arsenic affects the normal function of rat's liver. The adverse effects are more severe with exposure time increasing. The upexpression of MRP2 may play an important role for the bile secretion of arsenite and its metabolites.