Beneficial effects of follistatin in hepatic ischemia-reperfusion injuries in rats.
BACKGROUND
Ischemia-reperfusion injury has been demonstrated in a variety of clinical settings. The morbidity associated with liver transplantation and major hepatic resections is partly a result of ischemia-reperfusion injury. Follistatin, an activin-binding protein, binds to activins and subsequently blocks their action. It was reported that blockade of the action of activin with administration of follistatin accelerates recovery from ischemia renal injury. This study was conducted to investigate the involvement of the activin-follistatin system in hepatic ischemia-reperfusion injury.


METHODS
Total hepatic ischemia for 30 min was performed followed by reperfusion in a rat model. Rats were divided into two groups: a follistatin group and a control group. Follistatin (1 μg/body), which is an activin-binding protein, was administered at the time of reperfusion.


RESULTS
Though 80% of animals survived in the follistatin group, four of five animals died in the control group within 3 days after reperfusion (p<0.05). AST was significantly lower at 3 h after reperfusion in the follistatin group (p<0.05). LDH was also lower at 6 h after reperfusion in the follistatin group (p<0.05). Follistatin inhibited the mRNA expression of the βA subunit of activin. Moreover, the expression of IL-6, which is an inflammatory cytokine, was suppressed at 6 h after reperfusion in the follistatin group (p<0.05).


CONCLUSIONS
The present study demonstrated that treatment with follistatin reduced the expression of IL-6 and activin resulting in beneficial support for hepatic ischemia-reperfusion injuries.
Kanamoto
Mami
M
Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15, Kuramoto, Tokushima, 770-8503, Japan. kanamoto@clin.med.tokushima-u.ac.jp
Shimada
Mitsuo
M
Morine
Yuji
Y
Yoshizumi
Tomoharu
T
Imura
Satoru
S
Ikegami
Toru
T
Mori
Hiroki
H
Arakawa
Yusuke
Y
D028341:Activins / Q000096:biosynthesis; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D038681:Follistatin / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000293:injuries; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome
D038681:Follistatin; D015850:Interleukin-6; D028341:Activins; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
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