Human adrenomedullin combined with human adrenomedullin binding protein-1 is protective in gut ischemia and reperfusion injury in the rat

Zhang, Fangming; Wu, Rongqian; Zhou, Mian; Blau, Steven; Wang, Haichao

doi:10.1016/j.regpep.2008.09.007

Cited by 10 publications

(13 citation statements)

References 48 publications

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“…This is in accordance with previous studies that demonstrated the beneficial action of AM after ischemia-reperfusion injury in other organs [52,59,84,105]. Administration of AM/AMBP-1 downregulates gene expression and protein levels of proinflammatory cytokines, such as TNF-a and IL-6, in the small intestine, preserves gut barrier function, reduces remote organ injury improving perfusion both locally and systemically, and improves survival rate [190,191].…”

Section: Adrenomedullin Protects Against Intestinal Ischemiasupporting

confidence: 91%

“…There is emerging evidence that co-administration of AM and AMBP-1 should be considered as a novel approach to prevent injury after gut ischemia [190]. This is in accordance with previous studies that demonstrated the beneficial action of AM after ischemia-reperfusion injury in other organs [52,59,84,105].…”

Section: Adrenomedullin Protects Against Intestinal Ischemiasupporting

confidence: 88%

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Adrenomedullin regulates intestinal physiology and pathophysiology

Martínez-Herrero

Martı́nez

2016

Domestic Animal Endocrinology

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Section: Adrenomedullin Protects Against Intestinal Ischemiasupporting

confidence: 91%

Section: Adrenomedullin Protects Against Intestinal Ischemiasupporting

confidence: 88%

Adrenomedullin regulates intestinal physiology and pathophysiology

Martínez-Herrero

Martı́nez

2016

Domestic Animal Endocrinology

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“…Our survival study showed that human AM/AMBP-1 treatment significantly improved the survival from 41% to 81%, which was mostly seen on day 1. Organ injury markers have been used as measures to determine the degree of damage caused by models of organ injury such as sepsis, hemorrhagic shock, and ischemia/reperfusion injury 17,21,22,25 . These markers provide a way to compare the severity of damage to that is seen in clinical scenarios.…”

Section: Discussionmentioning

confidence: 99%

“…The THI rats with vehicle treatment received low dose of human albumin for a period of 30 min. The dosage of AM/AMBP-1 was similar to that was used recently in a rat model of gut ischemia and reperfusion injury 21 .…”

Section: Methodsmentioning

confidence: 99%

Resuscitation of Uncontrolled Traumatic Hemorrhage Induced by Severe Liver Injury: The Use of Human Adrenomedullin and Adrenomedullin Binding Protein-1

Shah

Jacob²,

Rajan³

et al. 2010

Journal of Trauma: Injury, Infection &Amp; Critical Care

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Background The liver is a major organ that is susceptible to injury following blunt and/or penetrating trauma to the abdomen. No specific non-operative treatment exists for traumatic hepatic injury (THI). Adrenomedullin (AM), a vasoactive peptide, combined with its binding protein (AMBP-1) is beneficial in various disease conditions. In this study, we propose to determine whether human AM combined with human AMBP-1 provides benefit in a model of THI in the rat. Methods Male adult rats were subjected to trauma-hemorrhage by resection of approximately 50% of total liver tissues and allowed bleeding for 15 min. Immediately thereafter, human AM (48 μg/kg BW) plus human AMBP-1 (160 μg/kg BW) was given intravenously over 30 min in 1 ml normal saline. After 4 h, the rats were euthanized, blood was collected, and tissue injury indicators were assessed. A 10-day survival study was also conducted. Results At 4 h after THI, plasma AMBP-1 levels were markedly decreased. Plasma levels of liver injury indicators (i.e., AST, ALT and LDH) were significantly increased after THI. Likewise, lactate, creatinine and TNF-α levels were significantly increased following THI. Administration of human AM/AMBP-1 after THI produced significant decreases of 64%, 23% and 19% of plasma AST, ALT and LDH levels, respectively. Similarly, plasma levels of lactate, creatinine and TNF-α were also decreased by 42%, 28% and 46% following human AM/AMBP-1 treatment, respectively. In a 10-day survival study, while vehicle treatment produced 41% survival, human AM/AMBP-1 treatment improved the survival rate to 81%. Conclusions Administration of human AM/AMBP-1 significantly attenuated tissue injury and inflammation, and improved survival following THI. Thus, human AM/AMBP-1 can be developed as a novel treatment for victims with uncontrolled traumatic hemorrhage.

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“…These initial studies were conducted with rat AM and human AMBP-1. Recently, we have also reported that combined treatment of human AM and human AMBP-1 reduced organ injury and inflammatory responses, and improved survival in rat models of hemorrhagic shock and gut ischemia/reperfusion injury (30, 31). In the current study, we examined whether administration of human AM combined with human AMBP-1 can minimize or prevent the damage induced by acute renal I/R injury in rats.…”

Section: Introductionmentioning

confidence: 97%

Attenuation of Renal Ischemia and Reperfusion Injury by Human Adrenomedullin and its Binding Protein

Shah

Rajan

Jacob

et al. 2010

Journal of Surgical Research

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Background Acute renal failure secondary to ischemia and reperfusion (I/R) injury poses a significant burden on both surgeons and patients. It carries a high morbidity and mortality rate and no specific treatment currently exists. Major causes of renal I/R injury include trauma, sepsis, hypoperfusion, and various surgical procedures. We have demonstrated that adrenomedullin (AM), a novel vasoactive peptide, combined with AM binding protein-1 (AMBP-1), which augments the activity of AM, is beneficial in various disease conditions. However, it remains unknown whether human AM/AMBP-1 provides any beneficial effects in renal I/R injury. The objective of our study therefore was to determine whether administration of human AM/AMBP-1 can prevent and/or minimize damage in a rat model of renal I/R injury. Methods Male adult rats were subjected to renal I/R injury by bilateral renal pedicle clamping with microvascular clips for 60 min followed by reperfusion. Human AM (12 µg/kg BW) and human AMBP-1 (40 µg/kg BW) or vehicle (52 µg/kg BW human albumin) were given intravenously over 30 min immediately following the clip removal (i.e., reperfusion). Rats were allowed to recover for 24 h post treatment, and blood and renal tissue samples were collected. Plasma levels of AM were measured using a radioimmunoassay specific for rat AM. Plasma AMBP-1 was measured by Western analysis. Renal water content and serum levels of systemic markers of tissue injury were measured. Serum and renal TNF-α levels were also assessed. Results At 24 h after renal I/R injury, plasma levels of AM were significantly increased while plasma AMBP-1 was markedly decreased. Renal water content and systemic markers of tissue injury (e.g., creatinine, BUN, AST and ALT) were significantly increased following renal I/R injury. Serum and renal TNF-α levels were also increased post injury. Administration of human AM/AMBP-1 decreased renal water content, and plasma levels of creatinine, BUN, AST and ALT. Serum and renal TNF-α levels were also significantly decreased after AM/AMBP-1 treatment. Conclusion Treatment with human AM/AMBP-1 in renal I/R injury significantly attenuated organ injury and the inflammatory response. Thus, human AM combined with human AMBP-1 may be developed as a novel treatment for patients with acute renal I/R injury.

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Human adrenomedullin combined with human adrenomedullin binding protein-1 is protective in gut ischemia and reperfusion injury in the rat

Cited by 10 publications

References 48 publications

Adrenomedullin regulates intestinal physiology and pathophysiology

Adrenomedullin regulates intestinal physiology and pathophysiology

Resuscitation of Uncontrolled Traumatic Hemorrhage Induced by Severe Liver Injury: The Use of Human Adrenomedullin and Adrenomedullin Binding Protein-1

Attenuation of Renal Ischemia and Reperfusion Injury by Human Adrenomedullin and its Binding Protein

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