ArticleNaunyn-Schmiedeberg's archives of pharmacology2025
Modulation of AMPK by esomeprazole and canagliflozin mitigates methotrexate-induced hepatotoxicity: involvement of MAPK/JNK/ERK, JAK1/STAT3, and PI3K/Akt signaling pathways.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed.
- Piribedil attenuates methotrexate-induced nephrotoxicity in rats: associated changes in miR-205/EGLN2, Nrf2, and PERK/ATF4/CHOP-related stress responses.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Olmesartan-Loaded PLGA Nanoparticles Attenuate Methotrexate-Induced Kidney Injury: Association with the AT1R/ERK1/2 Signaling Axis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Metabolomic, in vitro and preclinical evaluation of Auricularia polytricha mushroom.International microbiology : the official journal of the Spanish Society for Microbiology · 2026Article
- M2 macrophage-derived small extracellular vesicles carrying canagliflozin attenuate experimental asthma.Drug delivery and translational research · 2026Article
- Modulation of the ACLY-AMPK axis by bempedoic acid suppresses NF-κB-driven inflammation, VEGF-Notch angiogenic crosstalk, and cell-cycle progression in Solid Ehrlich Carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Fondaparinux attenuates methotrexate-induced hepatotoxicity by regulating coagulation, endothelial dysfunction, and inflammatory signaling via the TLR4/NLRP3 and NF-κB/IL-1β/MCP-1 pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Tempol Attenuates Methotrexate-Induced Osteotoxicity via Antioxidant Mechanisms: Impairment of Protection by GPX4 Inhibition Through ML210.Current issues in molecular biology · 2026Article
- Therapeutic potential of β-sitosterol in methotrexate-induced liver injury: association with STING and ERK-1 pathways.BMC gastroenterology · 2026Article
- Buspirone attenuates cyclophosphamide-induced renal dysfunction in association with alterations in miR-205/EGLN2, Nrf2, and PERK/ATF4/CHOP signaling.Frontiers in pharmacology · 2026Article
- Modulation of SIRT-1, NF-κB/TNF-α/IL-6, and ERK/Caspase-3 by Lutein Mitigates Methotrexate-Induced Hepatotoxicity.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Therapeutic potential of canagliflozin in DEN/TAA-induced renal cancer: mechanistic insights into NLRP3/IL-6/STAT3 and AMPK signaling and oxidative stress regulation.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
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 Tukey's post hoc test, with significance at p < 0.05. Results were presented as mean ± standard error (SE). Rats that received MTX showed significant liver damage, marked by elevated ALT, AST, MDA, MPO, iNOS, TNF-α, IL-6, and IL-1β levels (p < 0.01) and decreased antioxidant enzymes (HO-1, Nrf2, and GSH). Immunohistochemistry revealed increased NF-kB p65 and caspase-9 expression (p < 0.01), correlating with histopathological changes. Pretreatment with ESOM and CANA reduced liver enzyme levels, improved histology, restored antioxidant balance, and inhibited inflammatory pathways via p38MAPK/NF-kB p65 and JAK1/STAT3 (p < 0.01). Moreover, ESOM and CANA preserved PI3K/Akt activity and prevented caspase-dependent apoptosis (p < 0.01). Additionally, the combination treatment showed synergistic hepatoprotective effects, demonstrated by significant improvements in all measured parameters. These findings suggested that ESOM and CANA had significant potential as therapeutic agents for alleviating MTX-induced hepatotoxicity and warranted further investigation in future research.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.