Original Article
Copyright ©2014 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 28, 2014; 20(12): 3301-3311
Published online Mar 28, 2014. doi: 10.3748/wjg.v20.i12.3301
Regulatory effect and mechanisms of carbon monoxide-releasing molecule II on hepatic energy metabolism in septic mice
Feng Liang, Jie Cao, Wei-Ting Qin, Xu Wang, Xue-Feng Qiu, Bing-Wei Sun
Feng Liang, Jie Cao, Wei-Ting Qin, Xu Wang, Xue-Feng Qiu, Bing-Wei Sun, Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
Author contributions: Liang F, Cao J and Sun BW designed research; Liang F, Qin WT, Cao J and Qiu XF performed the experiment; Cao J and Qiu XF contributed new reagents/analytic tools; Sun BW and Liang F analyzed data; Sun BW wrote the paper.
Supported by National Natural Science Foundation of China, No. 30772256, No. 81071546 and No. 81272148; and Natural Science Foundation of Jiangsu Province, China, No. BK2012703
Correspondence to: Bing-Wei Sun, MD, PhD, Professor, Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, 438 Jiefang Road, Zhenjiang 212001, Jiangsu Province, China. sunbinwe@hotmail.com
Telephone: +86-511-85082258 Fax: +86-511-85029089
Received: November 11, 2013
Revised: December 20, 2013
Accepted: February 20, 2014
Published online: March 28, 2014
Processing time: 136 Days and 2.1 Hours
Abstract

AIM: To investigate the possible mechanisms of exogenous carbon monoxide-releasing molecule II (CORM-2) intervention on hepatic energy metabolism in experimental sepsis.

METHODS: Forty-eight C57BL/6 mice were randomly divided into four groups (n = 12): sham group; cecal ligation and puncture (CLP) group; CLP + CORM-2 group and CLP + iCORM-2 (inactive CORM-2) group. Survival rates were determined after 72 h. Twenty-four similarly treated mice (n = 6 in each group) were assayed for post-operative continuous blood glucose in the first 36 h. Thirty-six similarly treated mice (n = 9 in each group) underwent micro-positron emission tomography (PET) scanning after tail vein injection of 18F-fluorodeoxyglucose (FDG) 24 h after operation. Plasma and liver specimens were collected for assay of liver pathology, alanine transaminase (ALT) and aspartate transaminase (AST) activities. Hepatic glucokinase activity, lactic acid levels and mitochondrial swelling were also determined.

RESULTS: Improved survival was observed in CORM-2 treated mice. Both the CLP and CLP + CORM-2 groups had sustained low blood glucose levels within the first post-operative 36 h. 18F-FDG micro-PET images showed abnormally high levels of hepatic glucose metabolism (standardized uptake value) in the CLP group (2.76 ± 0.39 vs 0.84 ± 0.14, P < 0.01), which declined to normal levels after CORM-2 intervention (1.29 ± 0.32 vs 2.76 ± 0.39, P < 0.05). glucokinase activity was markedly increased in the CLP group (6.38 ± 0.56 U/g vs 4.60 ± 0.21 U/g, P < 0.01), but was normal after CORM-2 intervention (4.74 ± 0.14 U/g vs 6.38 ± 0.56 U/g, P < 0.05). CORM-2 suppressed plasma lactic acid levels (4.02 ± 0.02 mmol/L vs 7.72 ± 2.37 mmol/L, P < 0.05) and protected hepatic mitochondria in CLP mice. CORM-2 intervention also reduced elevated plasma AST (199.67 ± 11.08 U/L vs 379.67 ± 16.34 U/L, P < 0.05) and ALT (63.67 ± 12.23 U/L vs 112.67 ± 9.74 U/L, P < 0.05) activities in CLP mice.

CONCLUSION: The release of CO molecules by CORM-2 protects mitochondria and maintains a stable level of hepatic glucose metabolism. Thus, CORM-2 improves liver function and survival in septic mice.

Keywords: Sepsis; Carbon monoxide; Liver; Energy metabolism; Regulation

Core tip: This study used an exogenous carbon monoxide (CO) intervention for the first time and 18F-fluorodeoxyglucose/micro-positron emission tomography to detect hepatic glucose metabolism in vivo in septic mice. The protective effect of CO on hepatic mitochondria in septic mice was examined, and its regulatory effect on abnormal glucose metabolism was explored. The results will provide new evidence for potentially improving outcomes as a consequence of exogenous CO on the survival rate in septic patients.