Curcumin encapsulated in chitosan nanoparticles: a novel strategy for the treatment of arsenic toxicity.
Water-soluble nanoparticles of curcumin were synthesized, characterized and applied as a stable detoxifying agent for arsenic poisoning. Chitosan nanoparticles of less than 50 nm in diameter containing curcumin were prepared. The particles were characterized by TEM, DLS and FT-IR. The therapeutic efficacy of the encapsulated curcumin nanoparticles (ECNPs) against arsenic-induced toxicity in rats was investigated. Sodium arsenite (2mg/kg) and ECNPs (1.5 or 15 mg/kg) were orally administered to male Wistar rats for 4 weeks to evaluate the therapeutic potential of ECNPs in blood and soft tissues. Arsenic significantly decreased blood δ-aminolevulinic acid dehydratase (δ-ALAD) activity, reduced glutathione (GSH) and increased blood reactive oxygen species (ROS). These changes were accompanied by increases in hepatic total ROS, oxidized glutathione, and thiobarbituric acid-reactive substance levels. By contrast, hepatic GSH, superoxide dismutase and catalase activities significantly decreased on arsenic exposure, indicative of oxidative stress. Brain biogenic amines (dopamine, norepinephrine and 5-hydroxytryptamine) levels also showed significant changes on arsenic exposure. Co-administration of ECNPs provided pronounced beneficial effects on the adverse changes in oxidative stress parameters induced by arsenic. The results indicate that ECNPs have better antioxidant and chelating potential (even at the lower dose of 1.5 mg/kg) compared to free curcumin at 15 mg/kg. The significant neurochemical and immunohistochemical protection afforded by ECNPs indicates their neuroprotective efficacy. The formulation provides a novel therapeutic regime for preventing arsenic toxicity.
Division of Pharmacology and Toxicology, Defense Research and Development Establishment, Gwalior 474 002, India.
Abhishek
A
Yadav
Vinay
V
Lomash
M
M
Samim
Swaran J S
SJ
Flora
D000818:Animals; D001151:Arsenic / Q000493:pharmacokinetics / Q000633:toxicity*; D020261:Arsenic Poisoning / Q000097:blood / Q000188:drug therapy*; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003474:Curcumin / Q000008:administration & dosage* / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014018:Tissue Distribution
D001679:Biogenic Amines; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D005978:Glutathione; D003474:Curcumin; D001151:Arsenic