Authors
Maneesh Mohan, Abhishek Chauhan, Raj Kamal, Shareen Singh, Ankit Awasthi, Thakur Gurjeet Singh
Published in
Toxicology and applied pharmacology. Pages 118094. Oct 31, 2026. Epub Oct 31, 2026.
Abstract
Methylmercury chloride (CH₃HgCl)-induced neurotoxicity is associated with oxidative stress, neuroinflammation, glutamate dysregulation, apoptosis, and progressive neuronal injury. Chitinase-3-like protein 1 (CHI3L1) plays an important role in neuroinflammatory processes and represents a potential therapeutic target in neurodegenerative disorders. Kasugamycin is an aminoglycoside antibiotic primarily used in agriculture as a bactericide and fungicide. Beyond its agricultural applications, kasugamycin exhibits anti-inflammatory and immunomodulatory properties; however, its potential therapeutic application in neurological disorders is limited by poor brain penetration and limited pharmacokinetic characteristics. Therefore, this study aimed to investigate the neuroprotective potential of liposomal kasugamycin against CH₃HgCl-induced neurotoxicity in rats. Kasugamycin-loaded liposomes were prepared using the thin-film hydration technique and optimized through a Central Composite Design approach. The optimized formulation was characterized for physicochemical properties and in vitro drug release before evaluation in a rat model of CH₃HgCl-induced neurotoxicity. Neuroprotective efficacy was assessed using behavioral, biochemical, molecular, and histopathological parameters. The optimized formulation exhibited nanoscale particle size and high encapsulation efficiency. Liposomal kasugamycin significantly improved locomotor performance and body weight while attenuating oxidative stress, neuroinflammation, apoptosis-related alterations, glutamate dysregulation, and neuronal injury. Treatment restored superoxide dismutase (SOD) and reduced glutathione (GSH) levels while decreasing malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), Bax, caspase-3, and glutamate levels. Furthermore, liposomal kasugamycin increased Bcl-2 and myelin basic protein (MBP) expression and modulated CHI3L1 expression, suggesting potential involvement of neuroinflammatory and neuroprotective pathways. To the best of our knowledge, this study provides the first evidence of the neuroprotective potential of liposomal kasugamycin against CH₃HgCl-induced neurotoxicity, supporting further investigation of this formulation as a potential therapeutic strategy for mercury-associated neuronal injury.
PMID:
42966604
Bibliographic data and abstract were imported from PubMed on 01 Nov 2026.
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