Selenium Mitigates Caerulein and LPS-induced Severe Acute Pancreatitis by Inhibiting MAPK, NF-κB, and STAT3 Signaling via the Nrf2/HO-1 Pathway

Swetha, K. and Indumathi, M. C. and Kishan, R. and Siddappa, S. and Chen, C. H. and Marathe, G. K. (2025) Selenium Mitigates Caerulein and LPS-induced Severe Acute Pancreatitis by Inhibiting MAPK, NF-κB, and STAT3 Signaling via the Nrf2/HO-1 Pathway. Biological Trace Element Research, 203 (9). pp. 4728-4750. ISSN 0163-4984

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Abstract

Severe acute pancreatitis (SAP) leads to systemic inflammation, resulting in multiorgan damage. Acute lung injury and acute respiratory distress syndrome develop in one-third of SAP patients, with a high mortality rate of 60% due to secondary complications. Patients with pancreatitis often have selenium deficiency, and selenium supplements may provide beneficial effects. This study examined the protective role of selenium in a model of SAP induced by caerulein + lipopolysaccharide (cae + LPS). Mice were administered selenium (1 mg/kg) before being challenged with caerulein (6 injections of 50 mu g/kg) and LPS (10 mg/kg). At 3 h after the last caerulein injection, blood was collected for estimating pancreatic enzymes and cytokine levels, and the mice were euthanized. We performed morphological and histological studies, measured levels of protease and oxidative stress markers and conducted western blot, ELISA, and RT-qPCR analyses. We examined lung tissue histologically and estimated myeloperoxidase levels. Selenium pretreatment significantly reduced pancreatic enzyme levels such as amylase, lipase, and proteases (specifically MMPs) and reversed tissue injury in the pancreas and lungs caused by cae + LPS. In addition, selenium-treated mice showed decreased levels of inflammatory markers and chemokines. Examination of the downstream inflammatory pathways confirmed the protective effect of selenium, which mediates its anti-inflammatory and antioxidant action by inhibiting the major inflammatory signaling pathways (MAPKs, NF-kappa B, and STAT3) and activating the phosphorylation of Nrf2 via Nrf2/HO-1 pathways. These findings suggest that selenium may be a potential therapeutic option for treating SAP-associated secondary complications.

Item Type:	Article
Uncontrolled Keywords:	Severe acute pancreatitis (SAP), Caerulein , Systemic inflammation, Selenium, Nuclear-factor erythroid 2 related factor 2/ Heme oxygenase 1 (Nrf2/HO-1), Mitogen activated protein kinases (MAPKs).
Subjects:	C Chemical Science > Biochemistry
Divisions:	Department of > Biochemistry
Depositing User:	Ms Varalakshmi
Date Deposited:	30 Oct 2025 06:13
Last Modified:	30 Oct 2025 06:13
URI:	http://eprints.uni-mysore.ac.in/id/eprint/17884

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