ArticleDrug design, development and therapy2025
Mechanistic Insights into FOLFOX-Induced Neurotoxicity and Determination of Its Concentrations via a Novel, Simultaneous HPLC Quantification Method in Brain Tissue.
Article in Drug design, development and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: FOLFOX, a commonly prescribed chemotherapeutic regimen, associated with significant neurotoxicity, that necessitates stop administration in some cases, hence, this study aimed to investigate the molecular mechanisms underlying FOLFOX-induced neurotoxicity in the brain and sciatic nerve, and determining its cerebral concentration via HPLC technique. Methods: 48 rats were divided into four groups: normal control, Oxaliplatin (6 mg/kg), 5-Fluorouracil (50 mg/kg), and a combination group (oxaliplatin 6 mg/kg + 5-fluorouracil 50 mg/kg). Behavioral tests in addition to samples collection from cerebral tissues, sciatic nerves, and blood were conducted. Tissue histological and biochemical changes were determined, including oxidative stress markers (Nrf2, SOD2, HO-1), apoptotic proteins (Bax, cCaspase-3, Bcl-2), and inflammatory biomarkers (COX-II, TNF-α, IL-6, NF-κβ). A new HPLC method was developed and validated to quantify oxaliplatin and 5-fluorouracil (5-Flu) concentrations in the brain tissue. Results: Both oxaliplatin and 5-Flu induced a substantial oxidative stress, evidenced by reduced expression of Nrf2, SOD2, and HO-1 proteins, associated with a significant upregulation of the pro-apoptotic proteins Bax and cleaved caspase-3, and downregulation of the anti-apoptotic protein Bcl-2. Inflammatory markers were increased in all treated groups, and the highest levels were observed in the combination group. HPLC analysis confirmed a significantly higher concentration of both drugs in the cerebral tissue of the combination group. Histopathological findings revealed neuronal damage and inflammation associated by increased Glial fibrillary acidic protein (GFAP) and decreased neural cell adhesion molecule (NCAM) expression. Behavioral assessments demonstrated markedly reduced pain thresholds in treated animals. Conclusion: This study identified a novel mechanisms underlying FOLFOX neurotoxicity involving activation of the pro-apoptotic BAX/cCaspase-3 pathway and suppression of the Nrf2/KEAP-1/SOD2/HO-1 antioxidant defense mechanism. These disorders induced a neuronal injury, evidenced by altered GFAP and NCAM expression. The findings highlight the synergistic role of FOLFOX components in driving oxidative stress, apoptosis, and inflammation, collectively contributing to neurotoxicity.
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.