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Effect of IL-18 binding protein on hepatic ischemia-reperfusion injury induced by infrarenal aortic occlusion.

Ozsoy M, Gonul Y, Bal A, Ozkececi ZT, Celep RB, Adali F, Hazman O, Koçak A, Tosun M - Ann Surg Treat Res (2015)

Bottom Line: The proinflammatory cytokine levels had decreased in treatment group, and was statistically significant compared with the IR group.Serum levels of total oxidant status and oxidative stress index decreased and levels of total antioxidant status increased by IL-18BP.This study suggested that IL-18BP has antioxidant, anti-inflammatory and hepatoprotective effects in cases of IR with infrarenal AA induced liver oxidative damage.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Faculty of Medicine, Afyon Kocatepe University, Afyon, Turkey.

ABSTRACT

Purpose: Severe local and systemic tissue damage called ischemia/reperfusion (IR) injury occurs during the period of reperfusion. Free oxygen radicals and proinflammatory cytokines are responsible for reperfusion injury. IL-18 binding protein (IL-18BP) is a natural inhibitor of IL-18. The balance between IL-18 and IL-18BP has an important role in the inflammatory setting. The present study aimed to investigate whether IL-18BP had a protective role in remote organ hepatic IR injury.

Methods: Wistar-Albino rats were divided into three groups that contained seven rats. Group I (sham): Laparotomy and infrarenal abdominal aorta (AA) dissection were done but no clamping was done. Group II (I/R): The infrarenal AA was clamped by atraumatic microvascular clamp for 30 minutes and then was exposed to 90 minutes of reperfusion. Group III (IR + IL-18BP): 75 µg/kg of IL-18BP in 0.9% saline (1 mL) was administered 30 minutes before infrarenal AA dissection and clamping; 30 minutes of ischemia was applied and then was exposed to 90 minutes of reperfusion.

Results: Serum AST, ALT, and LDH levels were remarkably higher in IR group and returned to normal levels in treatment group. The proinflammatory cytokine levels had decreased in treatment group, and was statistically significant compared with the IR group. Serum levels of total oxidant status and oxidative stress index decreased and levels of total antioxidant status increased by IL-18BP.

Conclusion: This study suggested that IL-18BP has antioxidant, anti-inflammatory and hepatoprotective effects in cases of IR with infrarenal AA induced liver oxidative damage.

No MeSH data available.


Related in: MedlinePlus

(A) Inducible nitric oxide synthase (iNOS) staining for sham group. A few slight and mild immunopositive cells are seen around central veins which is normal because liver has massive metabolism, and oxygen saturation is considerably low especially around central veins (iNOS primary antibody, ×40). (B) iNOS staining for ischemia/reperfusion (IR) group. It is obviously seen that virtually whole hepatocyte cells were stained with iNOS from mild to heavy degrees (iNOS primary antibody, ×40). (C) Liver tissue taken from IR + IL-18 binding protein (IL-18BP) group stained with iNOS. Immunopositivity and number of the stained hepatocyteds are decreased and a few immunopositive cell clusters are seen in paranchyme (circles) (iNOS primary antibody, ×40). (D) General view of the liver tissue of sham group. Very slight edema is seen in paranchyme. But there is no inflammatory cell migration and sinusoidal enlargement (H&E, ×40). (E) Liver tissue taken from IR group. Slight edema, moderate sinusoidal enlargements, diffused necrotic cell groups (arrows) and mononuclear cell infiltration (asterix) are seen in paranchyme (H&E, ×40). (F) General view of the liver tissue of IR/IL-18 BP group. Very slight edema and slight sinusoidal enlargements are seen in paranchyme. But there is no inflammatory cell migration and there are a few necrotic cells (arrow) (H&E, ×40).
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Figure 1: (A) Inducible nitric oxide synthase (iNOS) staining for sham group. A few slight and mild immunopositive cells are seen around central veins which is normal because liver has massive metabolism, and oxygen saturation is considerably low especially around central veins (iNOS primary antibody, ×40). (B) iNOS staining for ischemia/reperfusion (IR) group. It is obviously seen that virtually whole hepatocyte cells were stained with iNOS from mild to heavy degrees (iNOS primary antibody, ×40). (C) Liver tissue taken from IR + IL-18 binding protein (IL-18BP) group stained with iNOS. Immunopositivity and number of the stained hepatocyteds are decreased and a few immunopositive cell clusters are seen in paranchyme (circles) (iNOS primary antibody, ×40). (D) General view of the liver tissue of sham group. Very slight edema is seen in paranchyme. But there is no inflammatory cell migration and sinusoidal enlargement (H&E, ×40). (E) Liver tissue taken from IR group. Slight edema, moderate sinusoidal enlargements, diffused necrotic cell groups (arrows) and mononuclear cell infiltration (asterix) are seen in paranchyme (H&E, ×40). (F) General view of the liver tissue of IR/IL-18 BP group. Very slight edema and slight sinusoidal enlargements are seen in paranchyme. But there is no inflammatory cell migration and there are a few necrotic cells (arrow) (H&E, ×40).

Mentions: Morphological change and H-Score results were given in Table 2 and Fig. 1. There was a prominent difference between the IR group and the other two groups by means of inflammatory cell infiltration (P < 0.05). Also, there was significant difference by means of sinusoidal enlargement and necrotic cell density mass between the IR applied only group and controls and between the IR and IR + IL18BP groups (P < 0.05) (Table 2, Fig. 1). In immunohistochemical evaluation, there was a prominent difference between the IR and sham groups (P = 0.001); between IR and IR + IL18BP groups (P = 0.026) by means of iNOS expression levels (Mean H-Score) (Table 2, Fig. 1).


Effect of IL-18 binding protein on hepatic ischemia-reperfusion injury induced by infrarenal aortic occlusion.

Ozsoy M, Gonul Y, Bal A, Ozkececi ZT, Celep RB, Adali F, Hazman O, Koçak A, Tosun M - Ann Surg Treat Res (2015)

(A) Inducible nitric oxide synthase (iNOS) staining for sham group. A few slight and mild immunopositive cells are seen around central veins which is normal because liver has massive metabolism, and oxygen saturation is considerably low especially around central veins (iNOS primary antibody, ×40). (B) iNOS staining for ischemia/reperfusion (IR) group. It is obviously seen that virtually whole hepatocyte cells were stained with iNOS from mild to heavy degrees (iNOS primary antibody, ×40). (C) Liver tissue taken from IR + IL-18 binding protein (IL-18BP) group stained with iNOS. Immunopositivity and number of the stained hepatocyteds are decreased and a few immunopositive cell clusters are seen in paranchyme (circles) (iNOS primary antibody, ×40). (D) General view of the liver tissue of sham group. Very slight edema is seen in paranchyme. But there is no inflammatory cell migration and sinusoidal enlargement (H&E, ×40). (E) Liver tissue taken from IR group. Slight edema, moderate sinusoidal enlargements, diffused necrotic cell groups (arrows) and mononuclear cell infiltration (asterix) are seen in paranchyme (H&E, ×40). (F) General view of the liver tissue of IR/IL-18 BP group. Very slight edema and slight sinusoidal enlargements are seen in paranchyme. But there is no inflammatory cell migration and there are a few necrotic cells (arrow) (H&E, ×40).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325650&req=5

Figure 1: (A) Inducible nitric oxide synthase (iNOS) staining for sham group. A few slight and mild immunopositive cells are seen around central veins which is normal because liver has massive metabolism, and oxygen saturation is considerably low especially around central veins (iNOS primary antibody, ×40). (B) iNOS staining for ischemia/reperfusion (IR) group. It is obviously seen that virtually whole hepatocyte cells were stained with iNOS from mild to heavy degrees (iNOS primary antibody, ×40). (C) Liver tissue taken from IR + IL-18 binding protein (IL-18BP) group stained with iNOS. Immunopositivity and number of the stained hepatocyteds are decreased and a few immunopositive cell clusters are seen in paranchyme (circles) (iNOS primary antibody, ×40). (D) General view of the liver tissue of sham group. Very slight edema is seen in paranchyme. But there is no inflammatory cell migration and sinusoidal enlargement (H&E, ×40). (E) Liver tissue taken from IR group. Slight edema, moderate sinusoidal enlargements, diffused necrotic cell groups (arrows) and mononuclear cell infiltration (asterix) are seen in paranchyme (H&E, ×40). (F) General view of the liver tissue of IR/IL-18 BP group. Very slight edema and slight sinusoidal enlargements are seen in paranchyme. But there is no inflammatory cell migration and there are a few necrotic cells (arrow) (H&E, ×40).
Mentions: Morphological change and H-Score results were given in Table 2 and Fig. 1. There was a prominent difference between the IR group and the other two groups by means of inflammatory cell infiltration (P < 0.05). Also, there was significant difference by means of sinusoidal enlargement and necrotic cell density mass between the IR applied only group and controls and between the IR and IR + IL18BP groups (P < 0.05) (Table 2, Fig. 1). In immunohistochemical evaluation, there was a prominent difference between the IR and sham groups (P = 0.001); between IR and IR + IL18BP groups (P = 0.026) by means of iNOS expression levels (Mean H-Score) (Table 2, Fig. 1).

Bottom Line: The proinflammatory cytokine levels had decreased in treatment group, and was statistically significant compared with the IR group.Serum levels of total oxidant status and oxidative stress index decreased and levels of total antioxidant status increased by IL-18BP.This study suggested that IL-18BP has antioxidant, anti-inflammatory and hepatoprotective effects in cases of IR with infrarenal AA induced liver oxidative damage.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Faculty of Medicine, Afyon Kocatepe University, Afyon, Turkey.

ABSTRACT

Purpose: Severe local and systemic tissue damage called ischemia/reperfusion (IR) injury occurs during the period of reperfusion. Free oxygen radicals and proinflammatory cytokines are responsible for reperfusion injury. IL-18 binding protein (IL-18BP) is a natural inhibitor of IL-18. The balance between IL-18 and IL-18BP has an important role in the inflammatory setting. The present study aimed to investigate whether IL-18BP had a protective role in remote organ hepatic IR injury.

Methods: Wistar-Albino rats were divided into three groups that contained seven rats. Group I (sham): Laparotomy and infrarenal abdominal aorta (AA) dissection were done but no clamping was done. Group II (I/R): The infrarenal AA was clamped by atraumatic microvascular clamp for 30 minutes and then was exposed to 90 minutes of reperfusion. Group III (IR + IL-18BP): 75 µg/kg of IL-18BP in 0.9% saline (1 mL) was administered 30 minutes before infrarenal AA dissection and clamping; 30 minutes of ischemia was applied and then was exposed to 90 minutes of reperfusion.

Results: Serum AST, ALT, and LDH levels were remarkably higher in IR group and returned to normal levels in treatment group. The proinflammatory cytokine levels had decreased in treatment group, and was statistically significant compared with the IR group. Serum levels of total oxidant status and oxidative stress index decreased and levels of total antioxidant status increased by IL-18BP.

Conclusion: This study suggested that IL-18BP has antioxidant, anti-inflammatory and hepatoprotective effects in cases of IR with infrarenal AA induced liver oxidative damage.

No MeSH data available.


Related in: MedlinePlus