Ferroptosis inhibition attenuates inflammatory response in mice with acute hypertriglyceridemic pancreatitis

Meng，Yi Teng1; Zhou，Yi2; Han，Pei Yu2; Ren，Hong Bo3

2023-04-21

10.3748/WJG.V29.I15.2294

World Journal of Gastroenterology   影响因子和分区

1007-9327

2219-2840

BACKGROUND Ferroptosis is involved in developing inflammatory diseases; yet, its role in acute hypertriglyceridemic pancreatitis (HTGP) remains unclear. AIM To explore whether ferroptosis is involved in the process of HTGP and elucidate its potential mechanisms. METHODS An HTGP mouse model was induced using intraperitoneal injection of P-407 and caerulein (CAE). Then, pancreatic tissues from the model animals were subjected to proteome sequencing analysis. The pathological changes and scores of the pancreas, lung, and kidney were determined using hematoxylin-eosin staining. The levels of serum amylase (AMY), triglyceride, and total cholesterol were measured with an automatic blood cell analyzer. Additionally, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were determined by enzyme linked immunosorbent assay. Malonaldehyde (MDA), glutathione (GSH), and Fe were detected in the pancreas. Finally, immunohistochemistry was performed to assess the expression of ferroptosis-related proteins. RESULTS Proteome sequencing revealed that ferroptosis was involved in the process of HTGP and that NADPH oxidase (NOX) 2 may participate in ferroptosis regulation. Moreover, the levels of serum AMY, TNF-α, IL-6, and IL-1β were significantly increased, MDA and Fe were upregulated, GSH and ferroptosis-related proteins were reduced, and the injury of the pancreas, lung, and kidney were aggravated in the P407 + CAE group compared to CAE and wild type groups (all P < 0.05). Notably, the inhibition of ferroptosis and NOX2 attenuated the pathological damage and the release of TNF-α, IL-6, and IL-1β in the serum of the mice. CONCLUSION Ferroptosis was found to have an important role in HTGP and may be considered a potential target for clinical treatment.

Acute hypertriglyceridemic pancreatitis Ferroptosis Ferrostatin-1 NADPH oxidase 2 Vas2870

SCI

英语

第一

Natural Science Foundation of Shandong Province[ZR2021MH032];

Gastroenterology & Hepatology

Gastroenterology & Hepatology

WOS:000981875100006

BAISHIDENG PUBLISHING GROUP INC

CLINICAL MEDICINE

2-s2.0-85156256142

Scopus

1.Department of Gastroenterology,Shenzhen People's Hospital,The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,Guangdong Province,518020,China
2.Wuxi School of Medicine,Jiangnan University,Wuxi,Jiangsu Province,214000,China
3.Department of Gastroenterology,Qilu Hospital,Jinan,Shandong Province,250012,China

Meng，Yi Teng,Zhou，Yi,Han，Pei Yu,et al. Ferroptosis inhibition attenuates inflammatory response in mice with acute hypertriglyceridemic pancreatitis[J]. World Journal of Gastroenterology,2023,29(15):2294-2309.

Meng，Yi Teng,Zhou，Yi,Han，Pei Yu,&Ren，Hong Bo.(2023).Ferroptosis inhibition attenuates inflammatory response in mice with acute hypertriglyceridemic pancreatitis.World Journal of Gastroenterology,29(15),2294-2309.

Meng，Yi Teng,et al."Ferroptosis inhibition attenuates inflammatory response in mice with acute hypertriglyceridemic pancreatitis".World Journal of Gastroenterology 29.15(2023):2294-2309.