Page 42 - Pharma News Letter Vol1 Issue2 - Converted By Dr. Ahmed Rashed

Chapter VI

1 publication affiliated with Faculty of Pharmacy
st
Mansoura National University

International Immunopharmacology

Volume 121, August 2023, 110442

Celecoxib abrogates concanavalin A-induced
hepatitis in mice: Possible involvement of Nrf2/
HO-1, JNK signaling pathways and COX-2
expression

Aya khaleel , Ahmed R. El-Sheakh 1,2,3 , Ghada
1
M. Suddek ,*
1
1 Department of Pharmacology and Toxicology,
Faculty of Pharmacy, Mansoura University,
Mansoura, Egypt.

2 Department of Pharmacology and Toxicology,
Faculty of Pharmacy, Mansoura National
University, Gamasa, Egypt. factor erythroid 2-related factor 2 (Nrf2) and

3 Future Studies and Risks Management’ the stress protein heme oxygenase-1 (HO-1)
National Committee of Drugs, Academy levels. Moreover, celecoxib 30 and 60 mg/
of Scientific Research, Ministry of Higher kg inhibited the release of proinflammatory
Education, Elsayeda Zeinab, Egypt. markers including IL-1β and TNF-α along
with significant decrease in p-JNK, AKT
Abstract phosphorylation ratio and caspase-3 expression.

Concanavalin A (ConA) is an established model Besides, Con A was correlated to high
for inducing autoimmune hepatitis (AIH) in expression of cyclooxygenase COX-2 and this
mice, mimicking clinical features in human. increasing was improved by administration
The aim of the current study is to explore of celecoxib. These changes were in good
the possible protective effect of celecoxib, a agreement with improvement in histological
cyclooxygenase-2 inhibitor, on immunological deterioration. The protective effect of celecoxib
responses elicited in the ConA model of acute was also associated with significant reduction
hepatitis. ConA (20 mg/kg) was administered of autophagy biomarkers (Beclin-1 and LC3II).
intravenously to adult male mice for 6 h. Prior In conclusion, celecoxib showed antioxidant,
to ConA intoxication, mice in the treated groups anti-inflammatory, anti-apoptotic and anti-
received daily doses of celecoxib (30 and 60 autophagy activity against Con A-induced
mg/kg in CMC) for 7 days. Results revealed immune-mediated hepatitis. These effects
that administration of celecoxib 60 mg/kg for could be produced by modulation of Nrf2/HO-
7 days significantly protected the liver from 1, IL-1B /p-JNK/p-AKT, JNK/caspase-3, and
ConA-induced liver damage revealed by Beclin-1/LC3II signaling pathways. https://doi.
significant decrease in ALT and AST serum org/10.1016/j.intimp.2023.110442
levels. Celecoxib 30 and 60 mg/kg pretreatment
enhanced oxidant/antioxidant hemostasis by
significant reduction of MDA and NO content
and increase hepatic GSH contents and SOD
activity. In addition, celecoxib 30 and 60 mg/
kg caused significant increase in hepatic nuclear

42 Faculty of Pharmacy Newsletter