[Effect of iron overload on experimental immunological liver injury in rats and the role of angiotensin].
OBJECTIVE
To investigate the effect of iron overload on experimental immunological liver injury in rats and the roles of losartan (LOS), which is the selective antagonist of angiotensin II receptor subtype AT1.


METHODS
Fifty male Wistar rats were divided by random into five groups (control, liver injury, liver injury + LOS, liver injury + ID and liver injury + ID + LOS). Immunological liver injury model was reproduceed by intravenous injection of BCG (Bacilli Calmette Guein) and then lipopolysaccharide (LPS). Iron overload model was created by intraperitoneal injection of iron dextran (ID). Serum iron (SI), transferrin (TRF), total protein (TP), the activity of asparatate aminotransferase (AST) and malondialdehyde (MDA) and liver iron (HIC) were tested. The expression of bcl-2 and Bax and the bax/bcl-2 ratio in hepatocyte were tested by flow cytometric analysis. Apoptotic index (AI) and proliferative index were also calculated.


RESULTS
(1) In comparison with blank control group, the activity of serum AST was higher. Serum TP and TRF were lower in liver injury animals. Liver MDA increased significantly and along with a lower SOD activity. The expression of Bax in liver injury group was significantly higher than that in control group. The bax/ bcl-2 ratio and AI increased significantly in liver injury group. (2) Compared with liver injury group, the animals treated with ID showed an increase of serum AST activity, increased MDA and the expression of bax, the bax/bcl-2 ratio and AI. HIC was higher than the control group. (3) Compared with liver injury group, the activity of serum AST was lower and TRF was higher, MDA was reduced and SOD activity increased in animals treated with LOS. The expression of bcl-2 was increased, bax/bcl-2 ratio and AI decreased in this group. (4) In comparison with ID treated liver injury animals, the activity of AST and the content of MDA, and TRF increased in the animals treated with ID plus LOS.


CONCLUSIONS
The immunological liver injury could be aggravated by iron overload through catalyzing lipid peroxidation and facilitating the apoptotic process of hepatocyte. Angiotensin faciliates in this kind of liver damage.
Zhuang
Jiaju
J
Physiological department of Bethune Military Medical College, Shijiazhuang 050081, China. zhuangjj@yahoo.com
Zhang
Yachao
Y
Zhang
Weili
W
Jiang
Hong
H
Liu
Huimin
H
Wang
Jing
J
D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000150:complications / Q000276:immunology* / Q000378:metabolism*; D007501:Iron / Q000097:blood; D019190:Iron Overload / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009163:Mycobacterium bovis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D047228:Angiotensin II Type 1 Receptor Blockers; D008070:Lipopolysaccharides; D000804:Angiotensin II; D007501:Iron; D019808:Losartan