Sorbitol dehydrogenase inhibitor protects the liver from ischemia/reperfusion-induced injury via elevated glycolytic flux and enhanced sirtuin 1 activity

Zhang,Changhe; Li,Xiangcheng; Liu,Qinhong

doi:10.3892/mmr.2014.2715

Sorbitol dehydrogenase inhibitor protects the liver from ischemia/reperfusion-induced injury via elevated glycolytic flux and enhanced sirtuin 1 activity

Authors:
- Changhe Zhang
- Xiangcheng Li
- Qinhong Liu
View Affiliations

Affiliations: Department of General Surgery, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China, Department of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: October 21, 2014 https://doi.org/10.3892/mmr.2014.2715
Pages: 283-288

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Sorbitol dehydrogenase (SDH), a key enzyme of the polyol pathway, has recently been demonstrated to have an important role in mediating tissue ischemia/reperfusion (I/R) injury. The present study investigated how this enzyme may affect the ischemic liver and the mechanism underlying its effect. Firstly, C57BL/6 mice were subjected to oral administration of CP‑470,711 (5 mg/kg body weight/day for five days) and 70% hepatic I/R. Next the present study further investigated the changes in liver function, histology, inflammation, apoptosis and necrosis; the cytosolic adenosine triphosphate (ATP) and nictotinamide adenine dinucleotide [NAD(H)] contents and the protein level of caspase 3 and sirtuin 1 (SIRT1). The data demonstrated that sorbitol dehydrogenase inhibitor (SDI)‑administration significantly alleviated I/R‑induced liver injury, palliated histological changes and lowered the level of hepatocyte apoptosis and necrosis. In addition, SDI‑pretreatment in ischemic liver markedly maintained the cytosolic ATP and NAD(H) proportion, enhanced SIRT1 and suppressed the activation of caspase 3 at the protein level. The findings in the present study revealed that the flux through SDH may render the liver more vulnerable to I/R-induced injury and interventions targeting this enzyme may provide a novel adjunctive approach to protect from severe tissue injury following liver ischemia.

View Figures

View References

1	Elias-Miró M, Massip-Salcedo M, Raila J, et al: Retinol binding protein 4 and retinol in steatotic and nonsteatotic rat livers in the setting of partial hepatectomy under ischemia/reperfusion. Liver Transpl. 18:1198–1208. 2012.PubMed/NCBI
2	Varona MA, Soriano A, Aguirre-Jaime A, et al: Statistical quality control charts for liver transplant process indicators: evaluation of a single-center experience. Transplant Proc. 44:1517–1522. 2012. View Article : Google Scholar : PubMed/NCBI
3	Tang WH, Wu S, Wong TM, Chung SK and Chung SS: Polyol pathway mediates iron-induced oxidative injury in ischemic-reperfused rat heart. Free Radic Biol Med. 45:602–610. 2008. View Article : Google Scholar : PubMed/NCBI
4	Li Q, Hwang YC, Ananthakrishnan R, et al: Polyol pathway and modulation of ischemia-reperfusion injury in Type 2 diabetic BBZ rat hearts. Cardiovasc Diabetol. 7:332008. View Article : Google Scholar : PubMed/NCBI
5	Tang WH, Kravtsov GM, Sauert M, et al: Polyol pathway impairs the function of SERCA and RyR in ischemic-reperfused rat hearts by increasing oxidative modifications of these proteins. J Mol Cell Cardiol. 49:58–69. 2010. View Article : Google Scholar : PubMed/NCBI
6	Chu-Moyer MY, Ballinger WE, Beebe DA, et al: SAR and species/stereo-selective metabolism of the sorbitol dehydrogenase inhibitor, CP-470,711. Bioorg Med Chem Lett. 12:1477–1480. 2002. View Article : Google Scholar : PubMed/NCBI
7	Schmidt RE, Dorsey DA, Beaudet LN, et al: A potent sorbitol dehydrogenase inhibitor exacerbates sympathetic autonomic neuropathy in rats with streptozotocin-induced diabetes. Exp Neurol. 192:407–419. 2005. View Article : Google Scholar
8	Ramalho FS, Alfany-Fernandez I, Casillas-Ramirez A, et al: Are angiotensin II receptor antagonists useful strategies in steatotic and nonsteatotic livers in conditions of partial hepatectomy under ischemia-reperfusion? J Pharmacol Exp Ther. 329:130–140. 2009. View Article : Google Scholar : PubMed/NCBI
9	Suzuki S, Toledo-Pereyra LH, Rodriguez FJ and Cejalvo D: Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK506 and cyclosporine. Transplantation. 55:1265–1272. 1993. View Article : Google Scholar : PubMed/NCBI
10	Berry MN and Friend DS: High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol. 43:506–520. 1969. View Article : Google Scholar : PubMed/NCBI
11	Wang S, Chen T, Chen R, et al: Emodin loaded solid lipid nanoparticles: preparation, characterization and antitumor activity studies. Int J Pharm. 430:238–246. 2012. View Article : Google Scholar : PubMed/NCBI
12	Lee HR, Kim HJ, Ko JS, et al: Comparative characteristics of porous bioceramics for an osteogenic response in vitro and in vivo. PLoS One. 8:e842722013. View Article : Google Scholar : PubMed/NCBI
13	Nikoletopoulou V, Markaki M, Palikaras K and Tavernarakis N: Crosstalk between apoptosis, necrosis and autophagy. Biochim Biophys Acta. 1883:3448–3459. 2013. View Article : Google Scholar
14	So PW and Fuller BJ: Enhanced energy metabolism during cold hypoxic organ preservation: studies on rat liver after pyruvate supplementation. Cryobiology. 46:295–300. 2003. View Article : Google Scholar : PubMed/NCBI
15	Katz NR: Metabolic heterogeneity of hepatocytes across the liver acinus. J Nutr. 122(Suppl): 843–849. 1992.PubMed/NCBI
16	Yu Q, Wang T, Zhou X, et al: Wld(S) reduces paraquat-induced cytotoxicity via SIRT1 in non-neuronal cells by attenuating the depletion of NAD. PLoS One. 6:e217702011. View Article : Google Scholar : PubMed/NCBI
17	Bantel H and Schulze-Osthoff K: Mechanisms of cell death in acute liver failure. Front Physiol. 3:792012. View Article : Google Scholar
18	Malhi H, Gores GJ and Lemasters JJ: Apoptosis and necrosis in the liver: a tale of two deaths? Hepatology. 43(Suppl 1): 31–44. 2006. View Article : Google Scholar : PubMed/NCBI
19	Brosnan JT, Krebs HA and Williamson DH: Effects of ischaemia on metabolite concentrations in rat liver. Biochem J. 117:91–96. 1970.PubMed/NCBI
20	Ying W: NAD+/NADH and NADP+/NADPH in cellular functions and cell death: regulation and biological consequences. Antioxid Redox Signal. 10:179–206. 2008. View Article : Google Scholar : PubMed/NCBI
21	Dodson M, Darley-Usmar V and Zhang J: Cellular metabolic and autophagic pathways: traffic control by redox signaling. Free Radic Biol Med. 63:207–221. 2013. View Article : Google Scholar : PubMed/NCBI
22	Ying W, Garnier P and Swanson RA: NAD+ repletion prevents PARP-1-induced glycolytic blockade and cell death in cultured mouse astrocytes. Biochem Biophys Res Commun. 308:809–813. 2003. View Article : Google Scholar : PubMed/NCBI
23	Hwang YC, Kaneko M, Bakr S, et al: Central role for aldose reductase pathway in myocardial ischemic injury. FASEB J. 18:1192–1199. 2004. View Article : Google Scholar : PubMed/NCBI
24	Ramasamy R, Trueblood N and Schaefer S: Metabolic effects of aldose reductase inhibition during low-flow ischemia and reperfusion. Am J Physiol. 275:H195–H203. 1998.PubMed/NCBI
25	Benavente CA and Jacobson EL: Niacin restriction upregulates NADPH oxidase and reactive oxygen species (ROS) in human keratinocytes. Free Radic Biol Med. 44:527–537. 2008. View Article : Google Scholar
26	Dong W, Li F, Pan Z, et al: Resveratrol ameliorates subacute intestinal ischemia-reperfusion injury. J Surg Res. 185:182–189. 2013. View Article : Google Scholar : PubMed/NCBI
27	Yan W, Fang Z, Yang Q, et al: SirT1 mediates hyperbaric oxygen preconditioning-induced ischemic tolerance in rat brain. J Cereb Blood Flow Metab. 33:396–406. 2013. View Article : Google Scholar : PubMed/NCBI
28	Lempiäinen J, Finckenberg P, Mervaala EE, et al: Caloric restriction ameliorates kidney ischaemia/reperfusion injury through PGC-1α-eNOS pathway and enhanced autophagy. Acta Physiol (Oxf). 208:410–421. 2013.PubMed/NCBI
29	Pillai JB, Isbatan A, Imai S and Gupta MP: Poly (ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity. J Biol Chem. 280:43121–43120. 2005. View Article : Google Scholar : PubMed/NCBI
30	Alano CC, Ying W and Swanson RA: Poly (ADP-ribose) polymerase-1-mediated cell death in astrocytes requires NAD⁺ depletion and mitochondrial permeability transition. J Biol Chem. 279:18895–18902. 2004. View Article : Google Scholar : PubMed/NCBI
31	Jang SY, Kang HT and Hwang ES: Nicotinamide-induced mitophagy: event mediated by high NAD⁺/NADH ratio and SIRT1 protein activation. J Biol Chem. 287:19304–19314. 2012. View Article : Google Scholar : PubMed/NCBI
32	Mouchiroud L, Houtkooper RH, Moullan N, et al: The NAD⁺/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell. 154:430–441. 2013.
33	Siegel C and McCullough LD: NAD⁺ depletion or PAR polymer formation: which plays the role of executioner in ischaemic cell death? Acta Physiol (Oxf). 203:225–234. 2011.