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Wortmannin, PI3K/Akt signaling pathway inhibitor, attenuates thyroid injury associated with severe acute pancreatitis in rats.
- Source :
-
International journal of clinical and experimental pathology [Int J Clin Exp Pathol] 2015 Nov 01; Vol. 8 (11), pp. 13821-33. Date of Electronic Publication: 2015 Nov 01 (Print Publication: 2015). - Publication Year :
- 2015
-
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.
- Subjects :
- Acute Disease
Amylases blood
Animals
Cytoprotection
Immunohistochemistry
Inflammation Mediators blood
Male
Malondialdehyde metabolism
Microscopy, Electron, Transmission
NF-kappa B metabolism
Pancreatitis blood
Pancreatitis enzymology
Pancreatitis pathology
Phosphatidylinositol 3-Kinase metabolism
Proto-Oncogene Proteins c-akt metabolism
Rats, Sprague-Dawley
Severity of Illness Index
Thyroid Diseases blood
Thyroid Diseases enzymology
Thyroid Diseases pathology
Thyroid Gland enzymology
Thyroid Gland ultrastructure
Thyroid Hormones blood
Wortmannin
p38 Mitogen-Activated Protein Kinases metabolism
Androstadienes pharmacology
Pancreatitis drug therapy
Phosphoinositide-3 Kinase Inhibitors
Protein Kinase Inhibitors pharmacology
Proto-Oncogene Proteins c-akt antagonists & inhibitors
Signal Transduction drug effects
Thyroid Diseases prevention & control
Thyroid Gland drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1936-2625
- Volume :
- 8
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- International journal of clinical and experimental pathology
- Publication Type :
- Academic Journal
- Accession number :
- 26823696