title: Wortmannin, PI3K/Akt signaling pathway inhibitor, attenuates thyroid injury associated with severe acute pancreatitis in rats.
abstract: Increasing evidences suggest that PI3K/AKT pathway plays an important role in the pathogenesis of inflammatory diseases such as acute pancreatitis. However, the exact effect of PI3K/AKT on thyroid injury associated with acute pancreatitis has not been investigated. This study aimed to investigate the protective effects of wortmannin, PI3K/AKT inhibitor, on thyroid injury in a rat model of severe acute pancreatitis (SAP). Sixty male SD rats were randomly divided into four groups: sham operating group (SO), SAP group, wortmannin treatment (WOR) group and drug control (WOR-CON) group. Serum amylase (AMY), lipase (LIP) and thyroid hormone levels were evaluated. The morphological change of thyroid tissue was analyzed under the light and transmission electron microscopy. AKT, P38MAPK and NF-κB expression in the thyroid tissue was evaluated by immunohistochemical staining. Oxidative stress and inflammatory cytokines were detected. Results showed that wortmannin attenuated the following: (1) serum AMY, LIP and thyroid hormone (2) pancreatic and thyroid pathological injuries (3) thyroid MDA, (4) thyroid ultrastructural change, (5) serum TNF-α, IL-6 and IL-1β (6) AKT, MAPKP38 and NF-κB expression in thyroid tissues. These results suggested that wortmannin attenuates thyroid injury in SAP rats, presumably because of its role on prevent ROS generation and inhibits the activation of P38MAPK, NF-κB pathway. Our findings provide new therapeutic targets for thyroid injury associated with SAP.
authors.affiliation: Department of General Surgery, Renmin Hospital of Wuhan University Wuhan 430060, China.
authors.forename: Ablikim
authors.initials: A
authors.lastname: Abliz
authors.affiliation: Department of General Surgery, Renmin Hospital of Wuhan University Wuhan 430060, China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of General Surgery, Renmin Hospital of Wuhan University Wuhan 430060, China.
authors.forename: Rongze
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Renmin Hospital of Wuhan University Wuhan 430060, China.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Renmin Hospital of Wuhan University Wuhan 430060, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Renmin Hospital of Wuhan University Wuhan 430060, China.
authors.forename: Weixing
authors.initials: W
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D019610:Cytoprotection; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D016328:NF-kappa B / Q000378:metabolism; D010195:Pancreatitis / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects*; D013959:Thyroid Diseases / Q000097:blood / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D013961:Thyroid Gland / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D013963:Thyroid Hormones / Q000097:blood; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000730:Androstadienes; D018836:Inflammation Mediators; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D013963:Thyroid Hormones; D008315:Malondialdehyde; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D000681:Amylases; D000077191:Wortmannin
keywords: NF-κB; P38MAPK; PI3K/AKT pathway; Severe acute pancreatitis; thyroid injury; wortmannin
references.citation: JAMA. 1981 Jan 2;245(1):43-5
references.pmid: 7431627
references.citation: Mol Cell Biol. 2001 Feb;21(3):893-901
references.pmid: 11154276
references.citation: Ter Arkh. 1988;60(9):50-2
references.pmid: 3217881
references.citation: Ann Surg. 1992 Jan;215(1):44-56
references.pmid: 1731649
references.citation: Thyroid. 1992 Summer;2(2):119-23
references.pmid: 1525579
references.citation: N Engl J Med. 1995 Dec 7;333(23):1562-3
references.pmid: 7477174
references.citation: Rev Esp Enferm Dig. 1998 Jan;90(1):15-22
references.pmid: 9558943
references.citation: Am J Physiol Gastrointest Liver Physiol. 2004 Dec;287(6):G1200-12
references.pmid: 15271649
references.citation: Chem Biol. 2005 Jan;12(1):99-107
references.pmid: 15664519
references.citation: Bioessays. 2005 Feb;27(2):153-63
references.pmid: 15666353
references.citation: J Endocrinol Invest. 2005 Mar;28(3):261-9
references.pmid: 15952412
references.citation: J Clin Endocrinol Metab. 2005 Aug;90(8):4559-65
references.pmid: 15886232
references.citation: J Clin Endocrinol Metab. 2005 Dec;90(12):6460-5
references.pmid: 16189257
references.citation: Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G875-86
references.pmid: 17158252
references.citation: J Pharmacol Exp Ther. 2008 Jan;324(1):306-12
references.pmid: 17921189
references.citation: Mol Med. 2008 Mar-Apr;14(3-4):160-6
references.pmid: 18224252
references.citation: Cell Biochem Funct. 2008 Jun;26(4):451-8
references.pmid: 18464293
references.citation: Antioxid Redox Signal. 2009 Jan;11(1):135-65
references.pmid: 18837654
references.citation: Adv Exp Med Biol. 2008;632:187-201
references.pmid: 19025123
references.citation: Clin Sci (Lond). 2009 Jun;116(11):791-804
references.pmid: 19397491
references.citation: Bioessays. 2010 Mar;32(3):185-96
references.pmid: 20162662
references.citation: Hormones (Athens). 2011 Apr-Jun;10(2):117-24
references.pmid: 21724536
references.citation: J Cell Sci. 2011 Aug 1;124(Pt 15):2591-601
references.pmid: 21750195
references.citation: Exp Mol Med. 2012 Jan 31;44(1):45-51
references.pmid: 22056625
references.citation: Chirurg. 2000 Mar;71(3):253-64
references.pmid: 10789041
references.citation: Chemosphere. 2015 Jan;118:229-38
references.pmid: 25278044
references.citation: Nature. 2001 May 17;411(6835):355-65
references.pmid: 11357143
references.citation: Curr Opin Investig Drugs. 2001 Apr;2(4):496-501
references.pmid: 11566005
references.citation: J Clin Invest. 2001 Nov;108(9):1387-95
references.pmid: 11696584
references.citation: Science. 2002 May 31;296(5573):1655-7
references.pmid: 12040186
references.citation: Am J Transplant. 2002 Jan;2(1):57-61
references.pmid: 12095057
references.citation: Gastroenterology. 2004 Feb;126(2):554-66
references.pmid: 14762792
references.citation: Toxicology. 2012 Dec 8;302(1):68-76
references.pmid: 22889935
references.citation: Pharmacol Rev. 2012 Oct;64(4):1027-54
references.pmid: 23023033
references.citation: PLoS One. 2013;8(2):e57442
references.pmid: 23460857
references.citation: PLoS One. 2013;8(11):e81767
references.pmid: 24312352
references.citation: World J Gastroenterol. 2014 Nov 7;20(41):15190-9
references.pmid: 25386068
references.citation: J Clin Endocrinol Metab. 1986 Jul;63(1):1-8
references.pmid: 3011834