Enhancement of P-glycoprotein expression by hepatocyte transplantation in carbon tetrachloride-induced rat liver.
The multidrug resistance protein P-glycoprotein (P-gp) is physiologically expressed at the bile canalicular membrane of the liver, where it participates in the biliary excretion of various lipophilic drugs. Chronic exposure to carbon tetrachloride (CCI(4)) is known to induce hepatic fibrosis resulting in hepatotoxicity. This study focuses on the effects of CCI(4) and hepatic transplantation (HT) on the P-gp expressions in rat liver. Male SD rats were treated with CCI(4) to induce liver damage for 3, 7, 14, 21, and 28 days, respectively. Immunohistochemistry revealed that P-gp was widely distributed in the liver and was spread from the cytoplasm to cell membrane of the rat liver. Western blot showed remarkable increase of P-gp expression in 3 days CCI(4)-treated rats, whereas, a continuous decrease in the P-gp expression was seen in 7, 14, 21, and 28 days CCI(4)-treated rats. After HT with cells from the normal rat liver, the level of P-gp increased comparing with those from the sham operation. Blood biochemistry showed decreased levels of serum alanine transaminase, aspartate transaminase, and alkaline phosphatase and increased serum levels of triglyceride and total protein, which indicated the improved function of the liver damaged by CCI(4). These results illustrate the variation of the expression of P-gp in CCI(4)-induced hepatic damage and an increase of P-gp level after HT in the toxic liver induced by CCI(4). We hypothesized that P-gp may play a protective role in the process of liver injury. HT can be beneficial to ameliorate the rat liver functional damage induced by CCI(4).
Yu
Ming
M
Department of Anatomy and Embryology, Peking University Health Science Center, Haidian District, Beijing, China.
Zhang
Weiguang
W
Qin
Lihua
L
Tian
Long
L
Zhou
Changman
C
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000378:metabolism*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001648:Bile Canaliculi / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000628:therapy; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase