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: Ablikim Abliz, Wenhong Deng, Rongze Sun, Wenyi Guo, Liang Zhao, Weixing Wang
• Journal: International journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 8 Issue 11 Pg. 13821-33 ( 2015) ISSN: 1936-2625 [Electronic] United States
• PMID: 26823696 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androstadienes
• Inflammation Mediators
• NF-kappa B
• Phosphoinositide-3 Kinase Inhibitors
• Protein Kinase Inhibitors
• Thyroid Hormones
• Malondialdehyde
• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt
• p38 Mitogen-Activated Protein Kinases
• Amylases
• Wortmannin

Topics

• Acute Disease
• Amylases (blood)
• Androstadienes (pharmacology)
• Animals
• Cytoprotection
• Immunohistochemistry
• Inflammation Mediators (blood)
• Male
• Malondialdehyde (metabolism)
• Microscopy, Electron, Transmission
• NF-kappa B (metabolism)
• Pancreatitis (blood, drug therapy, enzymology, pathology)
• Phosphatidylinositol 3-Kinase (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, metabolism)
• Rats, Sprague-Dawley
• Severity of Illness Index
• Signal Transduction (drug effects)
• Thyroid Diseases (blood, enzymology, pathology, prevention & control)
• Thyroid Gland (drug effects, enzymology, ultrastructure)
• Thyroid Hormones (blood)
• Wortmannin
• p38 Mitogen-Activated Protein Kinases (metabolism)