Secukinumab mitigates diethyl nitrosamine-induced acute liver injury in mice via modulating p-ERK/p-eIF2α/CHOP and NLRP3/Caspase-1/IL-1β pathways

Abstract

Secukinumab is a fully humanized monoclonal antibody which selectively targets IL-17A. It showed anti-inflammatory, neuroprotective, and antioxidant activity in many experimental studies. This study was aimed at exploring the hepatoprotective potential of secukinumab against diethylnitrosamine (DEN)-induced acute liver injury in mice, with an emphasis on its anti-inflammatory, antioxidant, and antipyroptotic properties. Thirty-six male mice were randomly divided into six groups-group one (Control): mice did not receive any treatment; group two (SEC20): mice received SEC (20 mg/kg, i.p.) only; group three (DEN group): mice received DEN (150 mg/kg, i.p.); group four (SEC5 + DEN): mice received SEC (5 mg/kg, i.p.) then injected with DEN 1 h after SEC administration; group five (SEC10 + DEN): mice received SEC (10 mg/kg, i.p.), then injected with DEN 1 h after SEC administration; and group six (SEC20 + DEN): mice received SEC (20 mg/kg, i.p.) then injected with DEN 1 h after SEC administration. Compared to DEN-injected mice, secukinumab at the dose of 5, 10, and 20 mg/kg significantly decreased serum levels of ALT, AST, GGT, and LDH as well as hepatic levels of MDA, IL-17A, p-ERK, p-eIF2α, CHOP, NLRP3, and IL-1β, in addition to increased serum level of albumin as well as hepatic levels of GSH and TAC. Histopathologically, secukinumab attenuated DEN-induced histopathological irregularities in hepatic tissues. Moreover, secukinumab markedly reduced the hepatic expression of NF-κB and Caspase-1. Secukinumab at the doses (5, 10, and 20 mg) showed hepatoprotective, antioxidant, and anti-inflammatory effects against DEN-induced hepatotoxicity in mice.