Protective Effects of Urinary Trypsin Inhibitor (UTI) on Hepatic Microvasculature in Hypotensive Brain-Dead Rats

Abstract

Background/Aims: We examined the protective effects of a protease inhibitor, urinary trypsin inhibitor (UTI), on livers of brain dead rats associated with systemic hemodynamic instability. Methods: Brain death was induced by inflating a balloon catheter placed in the epidural space in rats followed by intravenous administration of UTI for 6 h. The hemodynamic, functional and morphological changes in the liver were examined. Results: The induction of brain death resulted in a significant decrease in both mean arterial pressure (MAP) and hepatic tissue flow (HTF), and an increase in serum AST and cytokines such as tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant (CINC). An increase in the number of sequestered neutrophils and enhanced expressions of intercellular adhesion molecules (ICAM)-1 and CINC were also noted in the liver. The treatment with UTI significantly restored HTF to basal level without affecting MAP, and decreased the number of sequestered neutrophils in the hepatic sinusoids, suppressed the expression of ICAM-1 and CINC in the sinusoids, inhibited the production of serum TNF-α and CINC, and inactivated Kupffer cells. Conclusion: Intravenous administration of UTI is likely to ease unfavorable effects on the hepatic microvasculature evoked by brain death.

Methylprednisolone Therapy in Deceased Donors Reduces Inflammation in the Donor Liver and Improves Outcome After Liver Transplantation

“…27,28 Protease inhibitors such as urinary trypsin inhibitor decreased leukocyte recruitment and release of cytokines and proved its ability to restore hepatic tissue flow in the liver of hypotensive BD rats. 32 Another strategy is based on the cytoprotective and antioxidative properties of stress proteins such as metalloprotoporphyrin cobalt protoporphyrin, an inducer of HO-1. 30 In our present study, we performed donor therapy with methylprednisolone since this option offers the advantage of counteracting immunologic and also hormonal alterations caused by BD.…”

Circulating CXCL10 and IL-6 in solid organ donors after brain death predict graft outcomes

“…Experiments in animal models have previously demonstrated the relation between brain death and the rapid infiltration of leukocyte populations in peripheral organs with intense upregulation of their associated products 14 . Concordantly, human studies have suggested that brain death of potential organ donors induces an inflammatory response mediated by IL-1b, IL-6, TNF alpha, CXCL1, CCL2, CCL5 [39][40][41] that could affect graft quality and function 42,43 . Although our study is not without limitations, it has generated valuable indications.…”

Paradoxical effects of brain death and associated trauma on rat mesenteric microcirculation: an intravital microscopic study

“…It has been shown that BD enhances the expression of P-selectin (13). and ICAM-1 in the liver (13-15), kidney (9), and lungs (16). The data presented here demonstrated that the expression of P-selectin on mesenteric microvessels increased at 30 min with no further increase at the 180-min time point.…”