OBJECTIVE: To determine whether administration of a vasoactive peptide, human adrenomedullin (AM), in combination with its binding protein (ie, AMBP-1), prevents or minimizes hepatic ischemia-reperfusion (I/R) injury. SUMMARY BACKGROUND DATA: Hepatic I/R injury results from tissue hypoxia and subsequent inflammatory responses. Even though numerous pharmacological modalities and substances have been studied to reduce I/R-induced mortality, none have been entirely successful. We have shown that administration of AM/AMBP-1 produces significant beneficial effects under various pathophysiological conditions. However, it remains unknown if human AM/AMBP-1 has any protective effects on hepatic I/R-induced tissue damage and mortality. METHODS: Seventy percent hepatic ischemia was induced in male adult rats by placing a microvascular clip across the hilum of the left and median lobes for 90 minutes. After removing the clip, human AM alone, human AMBP-1 alone, human AM in combination with human AMBP-1 or vehicle was administered intravenously over a period of 30 minutes. Blood and tissue samples were collected 4 hours after reperfusion for various measurements. In additional groups of animals, the nonischemic liver lobes were resected at the end of 90-minute ischemia. The animals were monitored for 7 days and survival was recorded. RESULTS: After hepatic I/R, plasma levels of AM were significantly increased, whereas AMBP-1 levels were markedly decreased. Likewise, gene expression of AM in the liver was increased significantly, whereas AMBP-1 expression was markedly decreased. Administration of AM in combination with AMBP-1 immediately after the onset of reperfusion down-regulated inflammatory cytokines, decreased hepatic neutrophil infiltration, inhibited liver cell apoptosis and necrosis, and reduced liver injury and mortality in a rat model of hepatic I/R. On the other hand, administration of human AM alone or human AMBP-1 alone after hepatic I/R failed to produce significant protection. CONCLUSIONS: Human AM/AMBP-1 may be a novel treatment to attenuate tissue injury after an episode of hepatic ischemia.
OBJECTIVE: To determine whether administration of a vasoactive peptide, humanadrenomedullin (AM), in combination with its binding protein (ie, AMBP-1), prevents or minimizes hepatic ischemia-reperfusion (I/R) injury. SUMMARY BACKGROUND DATA: Hepatic I/R injury results from tissue hypoxia and subsequent inflammatory responses. Even though numerous pharmacological modalities and substances have been studied to reduce I/R-induced mortality, none have been entirely successful. We have shown that administration of AM/AMBP-1 produces significant beneficial effects under various pathophysiological conditions. However, it remains unknown if humanAM/AMBP-1 has any protective effects on hepatic I/R-induced tissue damage and mortality. METHODS: Seventy percent hepatic ischemia was induced in male adult rats by placing a microvascular clip across the hilum of the left and median lobes for 90 minutes. After removing the clip, humanAM alone, humanAMBP-1 alone, humanAM in combination with humanAMBP-1 or vehicle was administered intravenously over a period of 30 minutes. Blood and tissue samples were collected 4 hours after reperfusion for various measurements. In additional groups of animals, the nonischemic liver lobes were resected at the end of 90-minute ischemia. The animals were monitored for 7 days and survival was recorded. RESULTS: After hepatic I/R, plasma levels of AM were significantly increased, whereas AMBP-1 levels were markedly decreased. Likewise, gene expression of AM in the liver was increased significantly, whereas AMBP-1 expression was markedly decreased. Administration of AM in combination with AMBP-1 immediately after the onset of reperfusion down-regulated inflammatory cytokines, decreased hepatic neutrophil infiltration, inhibited liver cell apoptosis and necrosis, and reduced liver injury and mortality in a rat model of hepatic I/R. On the other hand, administration of humanAM alone or humanAMBP-1 alone after hepatic I/R failed to produce significant protection. CONCLUSIONS:HumanAM/AMBP-1 may be a novel treatment to attenuate tissue injury after an episode of hepatic ischemia.
Authors: C Nuki; H Kawasaki; K Kitamura; M Takenaga; K Kangawa; T Eto; A Wada Journal: Biochem Biophys Res Commun Date: 1993-10-15 Impact factor: 3.575
Authors: T Nishikimi; Y Saito; K Kitamura; T Ishimitsu; T Eto; K Kangawa; H Matsuo; T Omae; H Matsuoka Journal: J Am Coll Cardiol Date: 1995-11-15 Impact factor: 24.094
Authors: K Kitamura; K Kangawa; M Kawamoto; Y Ichiki; S Nakamura; H Matsuo; T Eto Journal: Biochem Biophys Res Commun Date: 1993-04-30 Impact factor: 3.575
Authors: John R Klune; Rajeev Dhupar; Shoko Kimura; Shinya Ueki; Jon Cardinal; Atsunori Nakao; Gary Nace; John Evankovich; Noriko Murase; Allan Tsung; David A Geller Journal: Am J Physiol Gastrointest Liver Physiol Date: 2012-06-28 Impact factor: 4.052
Authors: Maha M Sabry; Nagwa M Ramadan; Basant A Al Dreny; Laila A Rashed; Ayman Abo El Enein Journal: United European Gastroenterol J Date: 2019-01-23 Impact factor: 4.623