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Effects of Glycogen Synthase Kinase‐beta Inhibition in Ischemia‐Reperfusion Injury of the Liver
Author(s) -
Sepodes Bruno Miguel,
Rocha João Pedro,
EduardoFigueira Maria,
Thiemermann Christoph,
MotaFilipe Helder
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.235.4
Subject(s) - medicine , insulin , endocrinology , gsk 3 , glycogen , reperfusion injury , glycogen synthase , ischemia , gsk3b , kinase , biology , biochemistry
GSK‐3beta is a serine/threonine protein kinase involved in the modulation of inflammatory response. Here we investigate the effects of two GSK‐3beta inhibitors on the liver injury caused by ischemia‐reperfusion injury, in the rat, using a synthetic inhibitor, TDZD‐8, and the endogenous inhibitor, insulin. Male Wistar rats were randomly allocated as described: (1) Sham Group; (2) I/R Group: rats to which for 45 minutes the blood supply to ¾ of the liver was interrupted, plus by reperfusion for 2 h; (3) TDZD‐8 + I/R Group: rats received TDZD‐8 (1 mg/kg i.v.) 30 minutes prior to liver I/R; (4) Insulin + I/R Group: rats received insulin (1,4 UI/kg i.v.) 30 minutes prior to liver I/R; (5) TDZD‐8 and (6) Insulin Control Groups. Blood samples were obtained at the end of reperfusion and tissue samples for histology. Our results show that both TDZD‐8 and insulin administration reduced the increase on the level of biochemical markers for liver injury when compared to I/R group: AST (1132±61 vs. 541±254 and 555±10 IU/l, for TDZD‐8 and insulin, respectively) and ALT (1941±92 vs. 583±90 and 174±27 IU/l, for TDZD‐8 and insulin, respectively), and the same was observed for LDH and gamma‐GT, and light microscopy examination We demonstrate here that TDZD‐8 and insulin cause a substantial reduction in the ischemia‐reperfusion‐induced increase in the serum levels of hepatic injury markers, providing, to our knowledge for the first time, the evidence that inhibition of GSK‐3beta reduces the liver injury induced by ischemia‐reperfusion, in the rat. We propose that GSK‐3beta inhibitors, such as TDZD‐8 and insulin, may be useful in the therapy of liver injury associated with ischemia‐reperfusion of the organ.