Journal Article

Anti-inflammatory effects of moxifloxacin and levofloxacin on cadmium-activated human astrocytes: Inhibition of proinflammatory cytokine release, TLR4/STAT3, and ERK/NF-κB signaling pathway

Power, Christopher, Vivithanaporn, Pornpun, Suknuntha, Kran, Wonganan, Piyanuch, Sukwattanasombat, Jidapha, Phuagkhaopong, Suttinee

2025

Overview

Cadmium is a non-essential element and neurotoxin that causes neuroinflammation, which leads to neurodegenerative diseases and brain cancer. To date, there are no specific or effective therapeutic agents to control inflammation and alleviate cadmium-induced progressive destruction of brain cells. Fluoroquinolones (FQs), widely used antimicrobials with effective blood-brain barrier penetration, show promise in being repurposed as anti-inflammatory drugs. Therefore, we aimed to test the efficacy of repurposed FQs for the treatment of cadmium-induced inflammation using cultures of U-87 MG human astrocytes and primary human astrocytes. Both FQs abrogated cadmium-induced interleukin (IL)-6 and IL-8 release from human astrocytes in a concentration and time-dependent manner, although levofloxacin had a stronger inhibitory effect than moxifloxacin. The downregulation of inflammatory cytokine release occurred with a concomitant reduction in cadmium-induced elevations in p65 nuclear factor-κB (NF-κB) and extracellular signal-regulated kinases (ERKs) 1/2 phosphorylation. Additionally, levofloxacin treatment significantly alleviated cadmium-induced activation of phosphorylated NF-κB translocation and toll-like receptor (TLR)-4/signal transducer and activator of transcription (STAT) 3 signaling. Transcriptome analysis revealed that modulation of inflammation-related pathways was the most enriched after FQ treatment. Our data suggest that FQs, particularly levofloxacin, attenuate the inflammatory process mediated by cadmium in human astrocytes. These effects may be mediated, at least in part, by inhibition of immune pathways regulated by TLR4, STAT3, ERK MAPK, and NF-κB.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Amyotrophic lateral sclerosis / Anti-inflammatory agents / Anti-Inflammatory Agents - pharmacology / Antibiotics / Antimicrobial agents / Astrocytes / Astrocytes - drug effects / Astrocytes - metabolism / Bacterial infections / Biology and Life Sciences / Blood-brain barrier / Brain cancer / Brain research / Cadmium / Cadmium - toxicity / Cell culture / Cytokines / Cytokines - metabolism / Down-regulation / Effectiveness / Extracellular Signal-Regulated MAP Kinases - metabolism / Fluoroquinolones / Humans / Immunosuppressive agents / Inflammation / Kinases / Levofloxacin / Levofloxacin - pharmacology / MAP kinase / MAP Kinase Signaling System - drug effects / Medical research / Medicine and Health Sciences / Meningitis / Moxifloxacin / Moxifloxacin - pharmacology / Neurodegenerative diseases / Neurotoxicity / Neurotoxins / NF-kappa B - metabolism / NF-κB protein / Penicillin / Pharmacology / Phosphorylation / Physical Sciences / Poisoning / Signal transduction / Signal Transduction - drug effects / Stat3 protein / STAT3 Transcription Factor - metabolism / TLR4 protein / Toll-Like Receptor 4 - metabolism / Toll-like receptors / Toxins / Transcriptomes / Translocation