title: SPA0355 attenuates ischemia/reperfusion-induced liver injury in mice.
abstract: Hepatic ischemia/reperfusion (I/R) injury leads to oxidative stress and acute inflammatory responses that cause liver damage and have a considerable impact on the postoperative outcome. Much research has been performed to develop possible protective techniques. We aimed to investigate the efficacy of SPA0355, a synthetic thiourea analog, in an animal model of hepatic I/R injury. Male C57BL/6 mice underwent normothermic partial liver ischemia for 45 min followed by varying periods of reperfusion. The animals were divided into three groups: sham operated, I/R and SPA0355 pretreated. Pretreatment with SPA0355 protected against hepatic I/R injury, as indicated by the decreased levels of serum aminotransferase and reduced parenchymal necrosis and apoptosis. Liver synthetic function was also restored by SPA0355 as reflected by the prolonged prothrombin time. To gain insight into the mechanism involved in this protection, we measured the activity of nuclear factor-κB (NF-κB), which revealed that SPA0355 suppressed the nuclear translocation and DNA binding of NF-κB subunits. Concomitantly, the expression of NF-κB target genes such as IL-1β, IL-6, TNF-α and iNOS was significantly downregulated. Lastly, the liver antioxidant enzymes superoxide dismutase, catalase and glutathione were upregulated by SPA0355 treatment, which correlated with the reduction in serum malondialdehyde. Our results suggest that SPA0355 pretreatment prior to I/R injury could be an effective method to reduce liver damage.
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonbuk, Republic of Korea.
authors.forename: Ui-Jin
authors.initials: UJ
authors.lastname: Bae
authors.affiliation: Department of Surgery, Chonbuk National University Medical School, Jeonbuk, Republic of Korea.
authors.forename: Jae Do
authors.initials: JD
authors.lastname: Yang
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonbuk, Republic of Korea.
authors.forename: Sun-O
authors.initials: SO
authors.lastname: Ka
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonbuk, Republic of Korea.
authors.forename: Jeung-Hyun
authors.initials: JH
authors.lastname: Koo
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonbuk, Republic of Korea.
authors.forename: Seong Ji
authors.initials: SJ
authors.lastname: Woo
authors.affiliation: Department of Oral Biochemistry, Wonkwang University, Jeonbuk, Republic of Korea.
authors.forename: Young-Rae
authors.initials: YR
authors.lastname: Lee
authors.affiliation: Department of Surgery, Chonbuk National University Medical School, Jeonbuk, Republic of Korea.
authors.forename: Hee Chul
authors.initials: HC
authors.lastname: Yu
authors.affiliation: Department of Surgery, Chonbuk National University Medical School, Jeonbuk, Republic of Korea.
authors.forename: Baik Hwan
authors.initials: BH
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Hui-Yuan
authors.initials: HY
authors.lastname: Zhao
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Jae-Ha
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Division of Biotechnology, College of Environmental and Bioresource Sciences, Chonbuk National University, Jeonbuk, Republic of Korea.
authors.forename: Sang-Myeong
authors.initials: SM
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Raok
authors.initials: R
authors.lastname: Jeon
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonbuk, Republic of Korea.
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Park
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D048588:Benzoxazines / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000293:injuries* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013890:Thiourea / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D048588:Benzoxazines; D016328:NF-kappa B; C570784:SPA0355; D013890:Thiourea
references.citation: Hepatobiliary Pancreat Dis Int. 2006 Aug;5(3):436-42
references.pmid: 16911946
references.citation: J Clin Invest. 2005 Apr;115(4):849-59
references.pmid: 15776110
references.citation: Gastroenterology. 2003 Oct;125(4):1246-57
references.pmid: 14517806
references.citation: Ann Surg. 2004 Feb;239(2):220-31
references.pmid: 14745330
references.citation: J Hepatol. 2009 Aug;51(2):296-306
references.pmid: 19515451
references.citation: FASEB J. 1990 Dec;4(15):3355-9
references.pmid: 2253850
references.citation: Hepatol Res. 2008 May;38(5):429-40
references.pmid: 18034829
references.citation: Science. 1996 Nov 22;274(5291):1379-83
references.pmid: 8910279
references.citation: J Toxicol Sci. 2005 May;30(2):103-10
references.pmid: 15928458
references.citation: Hum Gene Ther. 2009 Oct;20(10):1133-42
references.pmid: 19534599
references.citation: J Hepatol. 2013 Nov;59(5):1094-106
references.pmid: 23811302
references.citation: J Hepatol. 2011 Aug;55(2):328-36
references.pmid: 21167234
references.citation: Am J Physiol. 1991 Mar;260(3 Pt 1):G355-62
references.pmid: 2003603
references.citation: Hepatol Int. 2009 Dec;3(4):526-36
references.pmid: 19941170
references.citation: Shock. 1996 Jan;5(1):34-40
references.pmid: 8821101
references.citation: J Gastroenterol Hepatol. 2011 Jan;26 Suppl 1:173-9
references.pmid: 21199529
references.citation: Hepatology. 1997 Jul;26(1):113-20
references.pmid: 9214459
references.citation: Am J Pathol. 2009 May;174(5):1776-85
references.pmid: 19349371
references.citation: J Surg Res. 2005 Apr;124(2):244-9
references.pmid: 15820254
references.citation: Br J Pharmacol. 2011 Sep;164(2b):794-806
references.pmid: 21501144
references.citation: Free Radic Biol Med. 2000 Oct 15;29(8):756-63
references.pmid: 11053777
references.citation: J Surg Res. 2013 Apr;180(2):e99-e106
references.pmid: 22560855
references.citation: J Hepatol. 2007 Dec;47(6):784-92
references.pmid: 17936399
references.citation: Exp Mol Med. 2013 Nov 01;45:e51
references.pmid: 24176948
references.citation: Gut. 2005 Jun;54(6):835-42
references.pmid: 15888794
references.citation: Science. 1998 Sep 11;281(5383):1680-3
references.pmid: 9733516
references.citation: Liver Transpl. 2006 Dec;12(12):1869-79
references.pmid: 17133584
references.citation: Transplantation. 2010 May 15;89(9):1050-6
references.pmid: 20160675
references.citation: World J Gastroenterol. 2005 Nov 28;11(44):6960-7
references.pmid: 16437600
references.citation: Hepatology. 2000 Aug;32(2):169-73
references.pmid: 10915720