Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Dec 7;14(45):6936-42.
doi: 10.3748/wjg.14.6936.

Effects of Wy14643 on hepatic ischemia reperfusion injury in rats

Si-Qi Xu  1 , Yuan-Hai Li, Sheng-Hong Hu, Ke Chen, Liu-Yi Dong
Affiliations

Effects of Wy14643 on hepatic ischemia reperfusion injury in rats

Si-Qi Xu et al. World J Gastroenterol. .

Abstract

Aim: To investigate the effects and possible mechanisms of Wy14643 on hepatic ischemia-reperfusion (I/R) injury in rats.

Methods: Thirty male Sprague-Dawley rats weighing 220-280 g were randomly divided into five experimental groups: sham group (G1, n=6): a sham operation was performed (except for liver I/R); I/R-untreated group (G2, n=6): rats underwent liver ischemia for 90 min followed by reperfusion for 4 h; and I/R+Wy14643 groups (G3, G4, G5; n=6): after the same surgical procedure as in group 2, animals were pretreated with Wy14643 at the dose of 1, 5 and 10 mg/kg 1 h before ischemia, respectively. Hepatic ischemia-reperfusion (I/R) was induced by clamping blood supply to the left lateral and median lobes of the liver for 90 min, and atraumatic clamp was removed for 4 h reperfusion. Blood samples and liver tissues were obtained at the end of reperfusion to assess serum and hepatic tissue homogenate aminotransferase (ALT), aspartate aminotransferase (AST), myeloperoxidase (MPO), serum interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha), as well as activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in the hepatic tissue homogenate.

Results: Hepatic I/R induced a significant increase in the serum levels of ALT, AST, TNF-alpha, IL-1beta and MPO, as well as the levels of ALT, AST and MDA in the liver tissue homogenate, which were reduced by pretreatment with Wy14643 at the dose of 1, 5 and 10 mg/kg, respectively. The activity of SOD in the liver tissue homogenate was decreased after hepatic I/R, which was enhanced by Wy14643 pretreatment. In addition, serum and liver tissue homogenate ALT and AST in the Wy14643 10 mg/kg group were lower than in the Wy14643 1 mg/kg and 5 mg/kg groups, respectively.

Conclusion: Wy14643 pretreatment exerts significant protection against hepatic I/R injury in rats. The protective effects are possibly associated with enhancement of anti-oxidant and inhibition inflammation response.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Levels of serum and liver tissue homogenate ALT and AST. Serum ALT (A), liver ALT (B), serum AST (C) and liver AST (D) levels in different groups (mean ± SD, n = 6). After 90 min of hepatic ischemia and 4 h of reperfusion, ALT and AST were determined with an ALT and AST assay kit. bP < 0.01 vs sham group; cP < 0.05, dP < 0.01 vs I/R group.
Figure 2
Figure 2
Ultrastructural alterations of liver tissue. A: Sham group. Normal appearance of mitochondrion, rough endoplasmic reticulum and nucleus structure; B: I/R group. Mitochondrion swelled significantly with vacuolar degeneration and mitochondrial crista destruction, marked decrease of rough endoplasmic reticulum and nucleus structure destruction; C: Wy14643 group (1 mg/kg). Mitochondrion swelled moderately, with mitochondrial crista interruption and vacuolar degeneration, increase of rough endoplasmic reticulum and nucleus structure destruction; D: Wy14643 group (5 mg/kg). Mitochondrion swelled mildly, with rough endoplasmic reticulu and normal nucleus structure; E: Wy14643 group (10 mg/kg). Normal appearance of mitochondrion, rough endoplasmic reticulum and nucleus structure.
Figure 3
Figure 3
Activities of MPO in the serum (A), activities of MPO in the liver (B), serum TNF-α levels (C), serum IL-1β levels (D), activity of SOD in the liver (E) and content of MDA in the liver (F) in different groups (mean ± SD, n = 6). After 90 min of hepatic ischemia and 4 h of reperfusion, MPO, TNF-α, IL-1β, SOD and MDA were analyzed with an MPO, TNF-α, IL-1β, SOD and MDA assay kit. bP < 0.01 vs sham group; cP < 0.05, dP < 0.01 vs I/R group.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Okaya T, Lentsch AB. Peroxisome proliferator-activated receptor-alpha regulates postischemic liver injury. Am J Physiol Gastrointest Liver Physiol. 2004;286:G606–G612. - PubMed
    1. Jaeschke H. Mechanisms of reperfusion injury after warm ischemia of the liver. J Hepatobiliary Pancreat Surg. 1998;5:402–408. - PubMed
    1. Jaeschke H, Farhood A. Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver. Am J Physiol. 1991;260:G355–G362. - PubMed
    1. Jaeschke H, Bautista AP, Spolarics Z, Spitzer JJ. Superoxide generation by neutrophils and Kupffer cells during in vivo reperfusion after hepatic ischemia in rats. J Leukoc Biol. 1992;52:377–382. - PubMed
    1. Jaeschke H, Smith CW. Mechanisms of neutrophil-induced parenchymal cell injury. J Leukoc Biol. 1997;61:647–653. - PubMed

MeSH terms