Differential expression of organic anion transporters in rats subjected to 70% or 90% hepatectomy.

BACKGROUND/AIMS: Differences in hepatic organic anion transporters were compared in rats to identify a causative factor for early stage acute hepatic failure after 70% or 90% hepatectomy (Hx). METHODOLOGY: Male Wistar rats (8 weeks, 250-330g) were randomly assigned to one of two groups for 70% Hx or 90% Hx, and sacrificed at 0, 6, 12, 24, 48, or 72 hours after Hx. Posthepatectomy expression of the bile salt export pump (Bsep), multidrug resistance proteins 2 and 3 (Mrp2, Mrp3), sodium-dependent taurocholate co-transporting polypeptide (Ntcp), and organic anion transporting polypeptides 1 and 2 (Oatp1, Oatp2) were analyzed by Northern blotting. Serum liver function tests were also performed. RESULTS: Postoperative survival rates at 72 hours after 70% and 90% Hx were 100% and 50%, respectively. mRNA expression of Bsep and Mrp3 was increased after 90% Hx, while decreased after 70% Hx. These values were significantly greater at 12 and 24 hours after 90% Hx than after 70% Hx (p < 0.05). In contrast, Mrp2 expression was downregulated to a half of the preoperative level after 90% Hx, while increased after 70% Hx. mRNA expression of uptake transporters (Ntcp, Oatp1, Oatp2) was decreased after 70% Hx and 90% Hx with a similar extent. Total serum bilirubin and bile acid levels were significantly increased after both hepatectomy procedures with a greater extent after 90% Hx. CONCLUSIONS: Alteration of mRNA expression of Bsep, Mrp2 and Mrp3 may be characteristic behavior in the early stage of acute liver failure.