A low dose of naloxone mitigates autoimmune hepatitis by regulating TLR4/NF-κB and Nrf2/HO-1 signaling pathways

Naloxone is a non-selective opiate receptor antagonist that is mainly used in the management of acute opioid overdose or intoxication. Previously, naloxone has been shown to have anti-inflammatory and antioxidant properties. Concanavalin A (Con A) model is a common and well established animal model...

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Bibliographic Details
Published in:Inflammopharmacology 2023-10, Vol.31 (5), p.2467-2478
Main Authors: Ibrahim, Kawther Magdy, Ahmed, Hebatalla I., Ramadan, Laila, Balah, Amany
Format: Article
Language:English
Subjects:
Allergology
Animals
Antioxidants - pharmacology
Biomedical and Life Sciences
Biomedicine
Concanavalin A - pharmacology
Cytokines
Dermatology
Gastroenterology
Hepatitis, Autoimmune - drug therapy
Humans
Immunology
MAP Kinase Signaling System
NF-E2-Related Factor 2
NF-kappa B
Original
Original Article
Pharmacology/Toxicology
Rheumatology
Toll-Like Receptor 4
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Summary:Naloxone is a non-selective opiate receptor antagonist that is mainly used in the management of acute opioid overdose or intoxication. Previously, naloxone has been shown to have anti-inflammatory and antioxidant properties. Concanavalin A (Con A) model is a common and well established animal model of autoimmune hepatitis that closely resembles the pathological alterations that occur in human. The present study demonstrates that a low dose of naloxone (LD NX) has the ability to improve hepatic function and attenuate hepatic damage induced by Con A as indicated by a clear reduction in serum aminotransferase, bilirubin and enhancement of albumin production as well as liver pathological changes. Also, The proinflammatory cytokines, tumor necrosis factor-α (TNF-α), interferon- γ (IFN-γ), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were highly suppressed in animals pretreated with LD NX via interference with TLR4/NF-κB as well as JNK signaling pathways. Furthermore, oxidative stress was highly attenuated in animals pretreated with LD NX as indicated by high reduction in hepatic MDA and an increase in Nrf2, HO-1 expression and subsequent production of the endogenous antioxidants, SOD, CAT and GSH. Collectively, this study demonstrates that LD NX has the ability to mitigate Con A-induced autoimmune hepatitis via modulation of inflammatory cytokines secretion and interference with reactive oxygen species generation.
ISSN:0925-4692
1568-5608
DOI:10.1007/s10787-023-01327-5