Subnormothermic machine perfusion of steatotic livers results in increased energy charge at the cost of anti-oxidant capacity compared to normothermic perfusion

Negin Karimian; Siavash Raigani; Viola Huang; Sonal Nagpal; Ehab O.A. Hafiz; Irene Beijert; Paria Mahboub; Robert J. Porte; Korkut Uygun; Martin Yarmush; Heidi Yeh

doi:10.3390/metabo9110246

Subnormothermic machine perfusion of steatotic livers results in increased energy charge at the cost of anti-oxidant capacity compared to normothermic perfusion

Negin Karimian^*
, Siavash Raigani^*
, Viola Huang^*
, Sonal Nagpal^*
, Ehab O.A. Hafiz^*
, Irene Beijert^*
, Paria Mahboub^*
, Robert J. Porte^*
, Korkut Uygun^*
, Martin Yarmush^*
, Heidi Yeh^*

^*Corresponding author for this work

Shriners Hospitals for Children
Theodore Bilharz Research Institute
University Medical Centre Groningen
Rutgers - The State University of New Jersey, New Brunswick
Harvard Medical School

Research output: Contribution to journal › Article › Academic › peer-review

20 Citations (Scopus)

31 Downloads (Pure)

Abstract

There continues to be significant debate regarding the most effective mode of ex situ machine perfusion of livers for transplantation. Subnormothermic (SNMP) and normothermic machine perfusion (NMP) are two methods with different benefits. We examined the metabolomic profiles of discarded steatotic human livers during three hours of subnormothermic or normothermic machine perfusion. Steatotic livers regenerate higher stores of ATP during SNMP than NMP. However, there is a significant depletion of available glutathione during SNMP, likely due to an inability to overcome the high energy threshold needed to synthesize glutathione. This highlights the increased oxidative stress apparent in steatotic livers. Rescue of discarded steatotic livers with machine perfusion may require the optimization of redox status through repletion or supplementation of reducing agents.

Original language	English
Article number	246
Pages (from-to)	1-13
Number of pages	13
Journal	Metabolites
Volume	9
Issue number	11
DOIs	https://doi.org/10.3390/metabo9110246
Publication status	Published - 24 Oct 2019
Externally published	Yes

Bibliographical note

Funding Information:
Funding: Funding from the US National Institutes of Health (grants R01DK096075, R01DK107875, R21EB020819, R01DK084053 and R01DK114506) and support from the Shriners Hospitals for Children is gratefully acknowledged.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.3390/metabo9110246Licence: CC BY

metabolites-09-00246Final published version, 3.41 MBLicence: CC BY

Cite this

Karimian, N., Raigani, S., Huang, V., Nagpal, S., Hafiz, E. O. A., Beijert, I., Mahboub, P., Porte, R. J., Uygun, K., Yarmush, M., & Yeh, H. (2019). Subnormothermic machine perfusion of steatotic livers results in increased energy charge at the cost of anti-oxidant capacity compared to normothermic perfusion. Metabolites, 9(11), 1-13. Article 246. https://doi.org/10.3390/metabo9110246

@article{3e9318784a2e400594cf84615455806c,

title = "Subnormothermic machine perfusion of steatotic livers results in increased energy charge at the cost of anti-oxidant capacity compared to normothermic perfusion",

abstract = "There continues to be significant debate regarding the most effective mode of ex situ machine perfusion of livers for transplantation. Subnormothermic (SNMP) and normothermic machine perfusion (NMP) are two methods with different benefits. We examined the metabolomic profiles of discarded steatotic human livers during three hours of subnormothermic or normothermic machine perfusion. Steatotic livers regenerate higher stores of ATP during SNMP than NMP. However, there is a significant depletion of available glutathione during SNMP, likely due to an inability to overcome the high energy threshold needed to synthesize glutathione. This highlights the increased oxidative stress apparent in steatotic livers. Rescue of discarded steatotic livers with machine perfusion may require the optimization of redox status through repletion or supplementation of reducing agents.",

author = "Negin Karimian and Siavash Raigani and Viola Huang and Sonal Nagpal and Hafiz, \{Ehab O.A.\} and Irene Beijert and Paria Mahboub and Porte, \{Robert J.\} and Korkut Uygun and Martin Yarmush and Heidi Yeh",

note = "Funding Information: Funding: Funding from the US National Institutes of Health (grants R01DK096075, R01DK107875, R21EB020819, R01DK084053 and R01DK114506) and support from the Shriners Hospitals for Children is gratefully acknowledged. Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2019",

month = oct,

day = "24",

doi = "10.3390/metabo9110246",

language = "English",

volume = "9",

pages = "1--13",

journal = "Metabolites",

issn = "2218-1989",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "11",

}

Karimian, N, Raigani, S, Huang, V, Nagpal, S, Hafiz, EOA, Beijert, I, Mahboub, P, Porte, RJ, Uygun, K, Yarmush, M & Yeh, H 2019, 'Subnormothermic machine perfusion of steatotic livers results in increased energy charge at the cost of anti-oxidant capacity compared to normothermic perfusion', Metabolites, vol. 9, no. 11, 246, pp. 1-13. https://doi.org/10.3390/metabo9110246

TY - JOUR

T1 - Subnormothermic machine perfusion of steatotic livers results in increased energy charge at the cost of anti-oxidant capacity compared to normothermic perfusion

AU - Karimian, Negin

AU - Raigani, Siavash

AU - Huang, Viola

AU - Nagpal, Sonal

AU - Hafiz, Ehab O.A.

AU - Beijert, Irene

AU - Mahboub, Paria

AU - Porte, Robert J.

AU - Uygun, Korkut

AU - Yarmush, Martin

AU - Yeh, Heidi

N1 - Funding Information: Funding: Funding from the US National Institutes of Health (grants R01DK096075, R01DK107875, R21EB020819, R01DK084053 and R01DK114506) and support from the Shriners Hospitals for Children is gratefully acknowledged. Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2019/10/24

Y1 - 2019/10/24

N2 - There continues to be significant debate regarding the most effective mode of ex situ machine perfusion of livers for transplantation. Subnormothermic (SNMP) and normothermic machine perfusion (NMP) are two methods with different benefits. We examined the metabolomic profiles of discarded steatotic human livers during three hours of subnormothermic or normothermic machine perfusion. Steatotic livers regenerate higher stores of ATP during SNMP than NMP. However, there is a significant depletion of available glutathione during SNMP, likely due to an inability to overcome the high energy threshold needed to synthesize glutathione. This highlights the increased oxidative stress apparent in steatotic livers. Rescue of discarded steatotic livers with machine perfusion may require the optimization of redox status through repletion or supplementation of reducing agents.

AB - There continues to be significant debate regarding the most effective mode of ex situ machine perfusion of livers for transplantation. Subnormothermic (SNMP) and normothermic machine perfusion (NMP) are two methods with different benefits. We examined the metabolomic profiles of discarded steatotic human livers during three hours of subnormothermic or normothermic machine perfusion. Steatotic livers regenerate higher stores of ATP during SNMP than NMP. However, there is a significant depletion of available glutathione during SNMP, likely due to an inability to overcome the high energy threshold needed to synthesize glutathione. This highlights the increased oxidative stress apparent in steatotic livers. Rescue of discarded steatotic livers with machine perfusion may require the optimization of redox status through repletion or supplementation of reducing agents.

UR - https://www.scopus.com/pages/publications/85084985560

U2 - 10.3390/metabo9110246

DO - 10.3390/metabo9110246

M3 - Article

C2 - 31652927

AN - SCOPUS:85084985560

SN - 2218-1989

VL - 9

SP - 1

EP - 13

JO - Metabolites

JF - Metabolites

IS - 11

M1 - 246

ER -

Subnormothermic machine perfusion of steatotic livers results in increased energy charge at the cost of anti-oxidant capacity compared to normothermic perfusion

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this