Abstract
Background
In the liver, eNOS appears to have a central role in protecting against ischemia/reperfusion
(I/R) injury. We hypothesized that tetrahydrobiopterin (BH4) would protect livers
subjected to I/R injury by coupling with eNOS.
Methods
Chinese Kun Ming (KM) mice were subjected to 60 min of 70% hepatic ischemia 30 min
after the administration of BH4 or saline. After reperfusion, survival was evaluated.
The histologic appearance and ALT, BH4, nitrite/nitrate, 8-isoprostane, and eNOS protein
expression levels were measured.
Results
The 1-wk survival rate was 66.67% in the BH4 group and 33.33% in the saline group.
The serum ALT values in the BH4 group 1, 3, 6, 12, and 24 h after reperfusion were
significantly lower than those of the saline group. A histologic examination of the
liver revealed only a small necrotic area in the BH4 group as opposed to massive necrosis
in the saline group. The percentage values of the hepatic necrotic area 24 h after
reperfusion were significantly less for the BH4 group than for the saline group. The
nitrite/nitrate levels in the liver tissue were significantly increased by ∼2-fold
in the BH4 group compared with the saline group. The free radical indicator 8-isoprostane
was reduced approximately 50% in the BH4 group compared with the saline group. Western
blotting showed that the level of eNOS protein between the groups was not significantly
different.
Conclusions
BH4 significantly improved the survival rate by reducing liver failure. This was supported
by the histologic findings, and the mechanism was explored. According to the results,
we suggest that BH4 prevents liver damage from I/R injury by attenuating reactive
oxygen species and increasing NO synthesis, and might provide a novel and promising
therapeutic option for preventing I/R injury.
Keywords
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Article info
Publication history
Published online: March 23, 2012
Accepted:
December 15,
2011
Received in revised form:
December 8,
2011
Received:
May 18,
2011
Identification
Copyright
© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
