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<p>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&#xa0;mg/kg, i.p.) only; group three (DEN group): mice received DEN (150&#xa0;mg/kg, i.p.); group four (SEC5 + DEN): mice received SEC (5&#xa0;mg/kg, i.p.) then injected with DEN 1&#xa0;h after SEC administration; group five (SEC10 + DEN): mice received SEC (10&#xa0;mg/kg, i.p.), then injected with DEN 1&#xa0;h after SEC administration; and group six (SEC20 + DEN): mice received SEC (20&#xa0;mg/kg, i.p.) then injected with DEN 1&#xa0;h after SEC administration. Compared to DEN-injected mice, secukinumab at the dose of 5, 10, and 20&#xa0;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&#xa0;mg) showed hepatoprotective, antioxidant, and anti-inflammatory effects against DEN-induced hepatotoxicity in mice.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月27日

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  • Zaid F. AL-rasheedi,
  • Omnia A. Nour,
  • Dalia H. El-Kashef

摘要

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.