Abstract

LOBENZARIT ATTENUATES CONCANAVALIN A-INDUCED AUTOIMMUNE HEPATITIS IN MICE

Reem A. Alzoubi*, Ahmed M. Awad1, Marwa E. Abdelmageed

ABSTRACT

Autoimmune hepatitis (AIH) is a liver injury illustrated by dysregulation in immune responses. Current options for AIH have limitations that highlight the urgent need to investigate alternative or adjunct therapeutic strategies for AIH management. We planned to explore the protecting action of Lobenzarit (LBZ) against concanavalin A (CON A)- provoked AIH in mice. Con A developed meaningful hepatic damage, evidenced by dysregulation in liver function biomarkers, marked inflammatory cell infiltration, and hepatocellular degeneration. The pretreatment of mice with LBZ (25 and 50 mg/kg, intraperitoneally) resulted in a significant ameliorative effect on these alterations in a dose-dependent manner. Additionally, LBZ significantly limited the CD4+ and CD8+ T-cell infiltration, thereby modulating adaptive immune amplification. Accordingly, LBZ restored redox homeostasis through Subsequently, LBZ improved liver function profiles and preserved hepatic architecture. Furthermore, LBZ obviously raised the dropped levels of TAC, GSH and SOD and markedly lowered hepatic MDA levels as competed to Con A-treated group. Our findings position LBZ as a promising immunomodulatory agent that targets both innate and adaptive responses.  

Keywords: Autoimmune hepatitis; Lobenzarit; ROCK; Innate immunity; oxidative stress.