Modulation of AMPK by esomeprazole and canagliflozin mitigates methotrexate-induced hepatotoxicity: involvement of MAPK/JNK/ERK, JAK1/STAT3, and PI3K/Akt signaling pathways.

ABSTRACT: This research investigated the hepatoprotective effects of esomeprazole (ESOM) and canagliflozin (CANA) against methotrexate-induced liver toxicity, focusing on AMPK modulation and its regulation of MAPK/JNK/ERK, JAK1/STAT3, and PI3K/Akt pathways. Fifty male Wistar rats were divided into five groups: control, MTX, and three pretreatment groups receiving ESOM (30 mg/kg), CANA (30 mg/kg), or their combination. ESOM and CANA were administered for 8 days before and 1 day after a single MTX injection (20 mg/kg, intraperitoneally) on day 9 to induce hepatotoxicity. Liver injury, oxidative stress, inflammation, and apoptosis were assessed using biochemical, histopathological, immunohistochemical, qRT-PCR, and western blot analyses. Data were analyzed by one-way analysis of variance (ANOVA) and Tu

SUBMITTER: El-Dessouki AM 

PROVIDER: S-EPMC12350602 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature