Citation
Muhammad, Mailafiya Maryam
(2019)
Therapeutic effects of curcumin-loaded cockle shell-derived CaCO₃ nanoparticles on lead-induced toxicity damage in a rat model.
Masters thesis, Universiti Putra Malaysia.
Abstract
Lead toxicity is an alarming global threat that intoxicates multiple organs particularly
the brain. Prolong lead exposure resulted into approximately 494,550 deaths and
contributed around 10% of intellectual disability globally. Recently the use of
curcumin (Cur) as an alternative therapy for the treatment of heavy metal-induced
toxicity is attracting nucleus attentions. Despite its remarkable pharmacological
activities, it remains clinically constrained due to its poor bioavailability when orally
administered. Currently cockle shell-derived calcium carbonate nanoparticle
(CSCaCO3NP) is gaining more acceptance in nanomedicine as a nanocarrier to various
therapeutics. Hence, this study was designed to evaluate the therapeutic effect of
curcumin-loaded CSCaCO3NP on lead-induced toxicity in rats. Synthesis of
CSCaCO3NP as a potential drug carrier for curcumin delivery was conducted using a
simple top-down method. The physicochemical properties of CSCaCO3NP and Cur-
CSCaCO3NP were characterized using standard techniques. Cur-CSCaCO3NP in vitro
kinetic release mechanism was evaluated using the dialysis bag membrane method.
Cytotoxicity assessment was carried out using WST’s assay. For in vivo study, thirtysix
male adults Sprague-Dawley rats were randomly assigned into five groups. All
groups contained six rats each apart from group A which contained 12 rats. All rats
apart from the rats in group A (control) were orally administered a flat dose of 50
mg/kg of lead for four weeks. Six rats from the control and group B were euthanized
for toxicity confirmatory tests at week four. Oral administration of curcumin (100
mg/kg) for group C and Cur-CSCaCO3NP (50 and 100 mg/kg) for group D and E
respectively, commenced at week 5 and ended in week 8. Motor function test was
performed using horizontal bar method and all rats were euthanize at the 8th week of
the experiment. Further, biochemical, histological and histochemical analysis were
performed. A spherical shaped CSCaCO3NP with a surface area of 14.48±0.1 m2/g,
mean diameter of 21.38±2.7 nm and a zeta potential of -18.5 mV was synthesized
which has a high loading capacity. The FT-IR and XRD revealed fewer observable changes on the peaks after conjugation. In vitro kinetic release profile demonstrated
slow and steady release at pH 1.2 compared to the rapid release at pH 7.4. WST’s
assay showed no apparent toxicity and high biocompatibility on normal cells. The
findings from the in vivo assessments revealed significant (p <0.05) impaired motor
functions, biochemical, haematological, histochemical and histological alterations in
lead-induced rats. Although, the rats treated with free curcumin showed some
ameliorative effects, Cur-CSCaCO3NP treatment demonstrated an enhanced
therapeutic effect through significant (p < 0.05) improvements on motor coordination,
haematological parameters, histochemical and histological features, increased SOD
activities and decreased MDA levels, when compared to free curcumin treatment. The
findings of the current study holds great prospects for Cur-CSCaCO3NP as a novel
approach for effective oral treatment of lead-induced neurodegenerations as well as
hepato-renal impairments.
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