Bromelain ameliorates hepatic microcirculation after warm ischemia
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Bromelain ameliorates hepatic microcirculation after warm ischemia. / Bahde, Ralf; Palmes, Daniel; Minin, Evgeni; Stratmann, Udo; Diller, Ricarda; Haier, Jörg; Spiegel, Hans-Ullrich.
In: J SURG RES, Vol. 139, No. 1, 01.05.2007, p. 88-96.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Bromelain ameliorates hepatic microcirculation after warm ischemia
AU - Bahde, Ralf
AU - Palmes, Daniel
AU - Minin, Evgeni
AU - Stratmann, Udo
AU - Diller, Ricarda
AU - Haier, Jörg
AU - Spiegel, Hans-Ullrich
PY - 2007/5/1
Y1 - 2007/5/1
N2 - BACKGROUND: Because of its immunomodulatory action, the protease bromelain represents a novel strategy for the treatment of hepatic ischemia/reperfusion (I/R) injury. A dose-response study was performed to investigate the effect of bromelain on liver function, microcirculation, and leukocyte-endothelium interactions in hepatic I/R injury.MATERIALS AND METHODS: One hundred forty rats were randomized to 8 short-term or 12 long-term groups (n=7 each). A 30 min normothermic hepatic ischemia was induced by Pringle maneuver with a portocaval shunt. Animals were treated 60 min prior to ischemia with either no therapy, 0.1, 1.0, or 10 mg/kg b.w. bromelain i.v. In the short-term experiments, microcirculation was investigated 30 min after sham operation or ischemia using intravital microscopy. In the long-term experiments AST, ALT, and bradykinin levels were determined for 14 d after central venous catheter (CVC) placement only, sham operation, or ischemia. Additionally, apoptosis rate, Kupffer cell activation, endothelial cell damage, and eNOS expression were analyzed.RESULTS: In sham-operated animals, treatment with 10 mg/kg b.w. bromelain led to a disturbed microcirculation with increased leukocyte adherence, apoptosis rate, Kupffer cell activation, and endothelial cell damage. Six h after CVC placement and administration of 10 mg/kg b.w. bromelain, AST and ALT levels were significantly increased. After I/R, rats treated with 0.1 mg/kg b.w. bromelain showed an improved microcirculation, reduction in leukocyte adhesion, apoptosis rates, Kupffer cell activation and endothelial cell damage, increased eNOS expression, and significantly lower AST levels compared with untreated animals.CONCLUSION: Bromelain represents a novel approach to the treatment of hepatic I/R injury with a limited therapeutic window.
AB - BACKGROUND: Because of its immunomodulatory action, the protease bromelain represents a novel strategy for the treatment of hepatic ischemia/reperfusion (I/R) injury. A dose-response study was performed to investigate the effect of bromelain on liver function, microcirculation, and leukocyte-endothelium interactions in hepatic I/R injury.MATERIALS AND METHODS: One hundred forty rats were randomized to 8 short-term or 12 long-term groups (n=7 each). A 30 min normothermic hepatic ischemia was induced by Pringle maneuver with a portocaval shunt. Animals were treated 60 min prior to ischemia with either no therapy, 0.1, 1.0, or 10 mg/kg b.w. bromelain i.v. In the short-term experiments, microcirculation was investigated 30 min after sham operation or ischemia using intravital microscopy. In the long-term experiments AST, ALT, and bradykinin levels were determined for 14 d after central venous catheter (CVC) placement only, sham operation, or ischemia. Additionally, apoptosis rate, Kupffer cell activation, endothelial cell damage, and eNOS expression were analyzed.RESULTS: In sham-operated animals, treatment with 10 mg/kg b.w. bromelain led to a disturbed microcirculation with increased leukocyte adherence, apoptosis rate, Kupffer cell activation, and endothelial cell damage. Six h after CVC placement and administration of 10 mg/kg b.w. bromelain, AST and ALT levels were significantly increased. After I/R, rats treated with 0.1 mg/kg b.w. bromelain showed an improved microcirculation, reduction in leukocyte adhesion, apoptosis rates, Kupffer cell activation and endothelial cell damage, increased eNOS expression, and significantly lower AST levels compared with untreated animals.CONCLUSION: Bromelain represents a novel approach to the treatment of hepatic I/R injury with a limited therapeutic window.
KW - Animals
KW - Bradykinin
KW - Bromelains
KW - Cytokines
KW - Dose-Response Relationship, Drug
KW - Female
KW - Immunohistochemistry
KW - Ischemia
KW - Kupffer Cells
KW - Liver Circulation
KW - Microscopy
KW - Rats
KW - Rats, Wistar
U2 - 10.1016/j.jss.2006.10.004
DO - 10.1016/j.jss.2006.10.004
M3 - SCORING: Journal article
C2 - 17292418
VL - 139
SP - 88
EP - 96
JO - J SURG RES
JF - J SURG RES
SN - 0022-4804
IS - 1
ER -