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. 2007 Apr 7;13(13):1953-61.
doi: 10.3748/wjg.v13.i13.1953.

Protective effect of curcumin against liver warm ischemia/reperfusion injury in rat model is associated with regulation of heat shock protein and antioxidant enzymes

Shi-Qiang Shen  1 , Yuan Zhang, Jin-Jian Xiang, Cheng-Long Xiong
Affiliations

Protective effect of curcumin against liver warm ischemia/reperfusion injury in rat model is associated with regulation of heat shock protein and antioxidant enzymes

Shi-Qiang Shen et al. World J Gastroenterol. .

Abstract

Aim: To investigate the hypothesis that the protective effects of curcumin in hepatic warm ischemia/reperfusion (I/R) injury are associated with increasing heat shock protein 70 (Hsp70) expression and antioxidant enzyme activity.

Methods: Sixty Sprague-Dawley male rats were randomly divided into sham, I/R, C + I/R groups. The model of reduced-size liver warm ischemia and reperfusion was used. Curcumin (50 mg/kg) was administered by injection through a branch of superior mesenteric vein at 30 min before ischemia in C + I/R group. Five rats were used to investigate the survival during 1 wk after operation in each group. Blood samples and liver tissues were obtained in the remaining animals after 3, 12, and 24 h of reperfusion to assess serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver tissue NO(2)(-) + NO(3)(-), malondialdehyde (MDA) content, superoxide dismutase (SOD), catalase (CAT), nitricoxide synthase (NOS) and myeloperoxidase (MPO) activity, Hsp70 expression and apoptosis ratio.

Results: Compared with I/R group, curcumin pretreatment group showed less ischemia/reperfusion-induced injury. CAT and SOD activity and Hsp70 expression increased significantly. A higher rate of apoptosis was observed in I/R group than in C + I/R group, and a significant increase of MDA, NO(2)(-) + NO(3)(-) and MPO level in liver tissues and serum transaminase concentration was also observed in I/R group compared to C + I/R group. Curcumin also decreased the activity of inducible NO synthase (iNOS) in liver after reperfusion, but had no effect on the level of endothelial NO synthase (eNOS) after reperfusion in liver. The 7 d survival rate was significantly higher in C + I/R group than in I/R group.

Conclusion: Curcumin has protective effects against hepatic I/R injury. Its mechanism might be related to the overexpression of Hsp70 and antioxidant enzymes.

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Figures

Figure 1
Figure 1
Significantly increased serum conce-ntrations of ALT (A) and AST (B) after reperfusion as compared with the sham group. Curcumin pretreatment significantly reduced the hepatic I/R-related elevation of ALT and AST levels. bP < 0.01 vs Sham group; dP < 0.01 vs C + I/R group. Error bars represent the 95% CI.
Figure 2
Figure 2
The results of SOD activity (A), CAT activity (B), MDA content (C), and total NO2- + NO3- level (D) in liver tissue. Curcumin pretreatment significantly reduced MDA content and total NO2- + NO3- levels, and increased CAT and SOD activity as compared to I/R group. aP < 0.05, bP < 0.01 vs Sham group; dP < 0.01 vs C + I/R group. Error bars represent the 95% CI.
Figure 3
Figure 3
Activity of MPO (A), iNOS (B), and eNOS (C) in liver tissue. aP < 0.05, bP < 0.01 vs sham group; dP < 0.01 vs C + I/R group. Error bars represent the 95% CI.
Figure 4
Figure 4
Expression of β-actin mRNA and Hsp70 mRNA in I/R group and C + I/R group. 6: 24 h after I/R in I/R group; 5: 24 h after I/R in C + I/R group; 4:12 h after I/R in I/R group; 3: 12 h after I/R in C + I/R group; 2: 3 h after I/R in I/R group; 1: 3 h after I/R in C + I/R group.
Figure 5
Figure 5
Expression of Hsp70mRNA (A) and Hsp70 (B) in C + I/R group increased after liver reperfusion as compared with I/R group. bP < 0.01 vs C + I/R group. Error bars represent the 95% confidence intervals.
Figure 6
Figure 6
In situ terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end labeling method for apoptosis detection in I/R group (A) and C + I/R group (B) at 24 h after operation.
Figure 7
Figure 7
Apoptosis index (analyzed in situ terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end labeling method) in C + I/R group after liver reperfusion as compared with I/R group. bP < 0.01 vs E2 + I/R group. Error bars represent the 95% CI.
Figure 8
Figure 8
Apoptosis ratio (analyzed by flow cytometry method) in C + I/R group after liver reperfusion as compared with sham group (A) and I/R group (B). bP < 0.01 vs sham group; dP < 0.01 vs C + I/R group. Error bars represent the 95% CI.
Figure 9
Figure 9
Seven-day-survival was significantly higher in C + I/R group than in I/R group. aP < 0.05, bP < 0.01 vs Sham group; cP < 0.05 vs C + I/R group.
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