Vesicular melatonin efficiently downregulates sodium fluoride-induced rat hepato- and broncho- TNF-α, TGF-β expressions, and associated oxidative injury: a comparative study of liposomal and nanoencapsulated forms

Abstract

Suvomoy Sana, Swarupa Ghosh, Nirmalendu Das, Sibani Sarkar, Ardhendu Kumar Mandal Drug Development, Diagnostics and Biotechnology, CSIR-Indian Institute of Chemical Biology, West Bengal, India Abstract: The importance of fluoride as a natural and industrial toxicant is recognized worldwide. We evaluated the regulating role and biological effect of vesicular (liposomal and nanoencapsulated) melatonin (N-acetyl-5-methoxytryptamine) for drug delivery and controlled release on the depletion of inflammatory mediators, as well as oxidative damage in sodium fluoride (NaF)-treated lungs and liver. Hepatic and bronchial damage was induced in Swiss albino rats with a single acute ingestion of NaF (48 mg/kg body weight, oral gavage). NaF exposure caused the generation of reactive oxygen species (ROS); upregulation of TNF-α and TGF-β; decreased activities of antioxidant systems (glutathione, glutathione-S-transferase, superoxide dismutase, catalase), succinate dehydrogenase, membrane microviscosity, and membrane potential; increased activity of lipid peroxidation and nicotinamide adenine dinucleotide hydride oxidase; and increased hepatic and nephrite toxicities (P<0.001) compared to those in normal animals. Charge (–ve/+ve)-specific single liposomal (dicetyl phosphate/stearylamine) and nanoencapsulated melatonin (4.46 mg/kg body weight, intravenous) treatments (2 hours after NaF exposure) significantly (P<0.01/0.001) and maximally (P<0.001) inhibited all alterations developed in NaF-mediated oxidative injuries in rat liver (+ve) and lungs (–ve), demonstrating their strong free radical scavenging, antioxidant and antigenotoxic properties, and vesicular efficiencies of targeting. Overall, these results suggest that nanoencapsulated melatonin might be considered as a more powerful remedial therapy in comparison to liposomes, in terms of its efficacy in regulating NaF-intoxicated oxidative injury. Keywords: sodium fluoride, reactive oxygen species, inflammatory mediators, oxidative injury, vesicular melatonin targeting

Keywords

• Sodium fluoride
• Reactive oxygen species
• Inflammatory mediators
• Oxidative injury
• Vesicular melatonin targeting