Curcumin-loaded cockle shell-derived calcium carbonate nanoparticles: a novel strategy for the treatment of lead-induced hepato-renal toxicity in rats

Lead (Pb) toxicity affects the hepatic and renal systems resulting to homeostasis imbalance. Curcumin is a strong antioxidant but has restrained clinical applications due to its poor bioavailability. Nanomedicine showed promising potentials in drug delivery and has brought forth the use of cockle shell-derived aragonite calcium carbonate nanoparticles (CSCaCO3NP) to enhance the effectiveness and targeted delivery of curcumin (Cur). Thus, this study aimed at evaluating the therapeutic effect of curcumin-loaded CSCaCO3NP (Cur- CSCaCO3NP) on lead-induced hepato-renal toxicity in rats. Thirty-six male adults Sprague-Dawley rats were randomly assigned into five groups. All groups contained six rats each except for 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 group A and B were euthanized after four weeks of lead induction. Oral administration of curcumin (100 mg/kg) for group C and Cur-CSCaCO3NP (50 and 100 mg/kg) for groups D and E respectively, commenced immediately after 4 weeks of lead induction which lasted for 4 weeks. All rats were euthanized at the 8th week of the experiment. Further, biochemical, histological and hematological analysis were performed. The findings revealed a biochemical, hematological and histological changes in lead-induced rats. However, treatments with the Cur-CSCaCO3NP and free curcumin reversed the aforementioned changes. Although, Cur-CSCaCO3NP presented better therapeutic effects on lead-induced toxicity in rats when compared to free curcumin as there was significant improvements in hematological, biochemical and histological changes which is parallel with attenuation of oxidative stress. The findings of the current study hold great prospects for Cur-CSCaCO3NP as a novel approach for effective oral treatment of lead-induced hepato-renal impairments

Cockle shell-derived calcium carbonate (aragonite) nanoparticles: a dynamite to nanomedicine

Cockle shell is an external covering of small, salt water edible clams (Anadara granosa) that dwells in coastal area. This abundant biomaterial is hard, cheap and readily available with high content of calcium carbonate in aragonite polymorphic form. At present, cockle shell-derived calcium carbonate nanoparticles (CSCaCO3NPs) with dual applications has remarkably drawn significant attention of researchers in nanotechnology as a nanocarrier for delivery of different categories of drugs and as bone scaffold due to its beneficial potentials such as biocompatibility, osteoconductivity, pH sensitivity, slow biodegradation, hydrophilic nature and a wide safety margin. In addition, CSCaCO3NP possesses structural porosity, a large surface area and functional group endings for electrostatic ion bonds with high loading capacity. Thus, it maintains great potential in the drug delivery system and a large number of biomedical utilisations. The pioneering researchers adopted a non-hazardous top-down method for the synthesis of CSCaCO3NP with subsequent improvements that led to the better spherical diameter size obtained recently which is suitable for drug delivery. The method is therefore a simple, low cost and environmentally friendly, which involves little procedural steps without stringent temperature management and expensive hazardous chemicals or any carbonation methods. This paper presents a review on a few different types of nanoparticles with emphasis on the versatile most recent advancements and achievements on the synthesis and developments of CSCaCO3NP aragonite with its applications as a nanocarrier for drug delivery in nanomedicine

Neurotherapeutic effects of curcumin on lead-induced toxicity in a rat model with emphasis on cerebellar damage

Lead (Pb) is a toxic environmental heavy metal that induces serious clinical defect on all organs with the brain, kidney and liver being the primary targets, hence Pb poisoning has been a major threat to public health in developing countries due to human activities. Curcumin is the main active constituent of turmeric rhizome (Curcuma longa) with great neuroprotective role as well as being a strong antioxidant and anti-inflammatory properties. This study is aimed at evaluating the therapeutic potentials of curcumin on Pb-induced toxicity in a rat model since the application of chelation therapy is associated with numerous side effects. Thirty-six male Sprague Dawley rats aged 8 weeks weighing between 200 – 250 g were randomly assigned into five (5) groups with 12 rats in Group A (normal saline) and 6 rats each for Group B (LTG) (50 mg/kg of lead acetate for 4 weeks), Group C (RC) (50 mg/kg lead acetate for 4 weeks and left for another 4 weeks without treatment), Group D (Cur100) (50 mg/kg lead acetate for 4 weeks, followed by 100 mg/kg curcumin for 4 weeks) and Group E (Cur200) (50 mg/kg lead acetate, followed by 200 mg/kg curcumin for 4 weeks). All experimental groups received the oral treatment through orogastric-tube on alternate days. Motor functions was assessed using horizontal bar method while Pb concentration in the cerebellum, liver and kidney of the rats were evaluated using inductive coupled plasma mass spectrometry (ICP-MS) techniques. Further, the rats’ cerebellum, liver and kidney were fixed in 10% buffered formalin for 5 days and subsequently prepared for histological examination using paraffin method. The Pbadministered rats showed significant decrease in motor activity scores, SOD activity with increase MDA levels and Pb concentration in their cerebellum, liver, kidney and serum with marked alterations in the histological architecture of the cerebellum, liver and kidney. However, treatment with curcumin improved their functional motor activity, reduced Pb concentration in the cerebellum, liver and kidney and ameliorates the markers of oxidative stress as well as attenuating the alterations in the histological architecture of the cerebellum, liver and kidney. Therefore, it is concluded that curcumin attenuates Pb-induced toxicity via inhibition of oxidative stress and chelating activity in rats

Curcumin Attenuates Lead-Induced Cerebellar Toxicity in Rats via Chelating Activity and Inhibition of Oxidative Stress

Lead (Pb) is a toxic, environmental heavy metal that induces serious clinical defects in all organs, with the nervous system being its primary target. Curcumin is the main active constituent of turmeric rhizome (Curcuma longa) with strong antioxidant and anti-inflammatory properties. This study is aimed at evaluating the therapeutic potentials of curcumin on Pb-induced neurotoxicity. Thirty-six male Sprague Dawley rats were randomly assigned into five groups with 12 rats in the control (normal saline) and 6 rats in each of groups, i.e., the lead-treated group (LTG) (50 mg/kg lead acetate for four weeks), recovery group (RC) (50 mg/kg lead acetate for four weeks), treatment group 1 (Cur100) (50 mg/kg lead acetate for four weeks, followed by 100 mg/kg curcumin for four weeks) and treatment group 2 (Cur200) (50 mg/kg lead acetate for four weeks, followed by 200 mg/kg curcumin for four weeks). All experimental groups received oral treatment via orogastric tube on alternate days. Motor function was assessed using a horizontal bar method. The cerebellar concentration of Pb was evaluated using ICP-MS technique. Pb-administered rats showed a significant decrease in motor scores and Superoxide Dismutase (SOD) activity with increased Malondialdehyde (MDA) levels. In addition, a marked increase in cerebellar Pb concentration and alterations in the histological architecture of the cerebellar cortex layers were recorded. However, treatment with curcumin improved the motor score, reduced Pb concentration in the cerebellum, and ameliorated the markers of oxidative stress, as well as restored the histological architecture of the cerebellum. The results of this study suggest that curcumin attenuates Pb-induced neurotoxicity via inhibition of oxidative stress and chelating activity

Ameliorative effect of curcumin on lead-induced hematological and hepatorenal toxicity in a rat model

Introduction: Lead (Pb) is a ubiquitous toxic heavy metal that inflicts numerous clinical consequences on humans. Curcumin is the principal component of turmeric, which is reported to have antioxidative properties. This study aimed at evaluating the ameliorative effects of curcumin on Pb-induced hepatorenal toxicity in a rat model. Methods: Thirty-six male Sprague-Dawley rats were randomly assigned into five groups with 12 rats in the control (normal saline) and six rats each for the lead-treated group (LTG) (50 mg/kg lead acetate [Pb acetate] for 4 weeks), recovery group (50 mg/kg Pb acetate for 4 weeks and left with no treatment for another 4 weeks), treatment group 1 (Cur100) (50 mg/kg Pb acetate for 4 weeks, followed by 100 mg/kg curcumin for 4 weeks), and treatment group 2 (Cur200) (50 mg/kg Pb acetate for 4 weeks, followed by 200 mg/kg curcumin for 4 weeks). All the experimental groups received oral treatments via orogastric-tube on alternate days. Pb concentration in the liver and kidney of the rats were evaluated using inductive-coupled plasma mass spectrometry techniques. Results: Pb-administered rats revealed significant alteration in oxidative status and increased Pb concentration in their liver and kidney with obvious reduction of hemogram and increased in leukogram as well as aberration in histological architecture of the liver and kidney. However, treatment with curcumin reduces the tissue Pb concentrations and ameliorates the above mention alterations. Conclusions: The results in this study suggested that curcumin attenuates Pb-induced hepatorenal toxicity via chelating activity and inhibition of oxidative stress

Cytotoxicity studies of curcumin loaded-cockle shell-derived calcium carbonate nanoparticles

Background: Cockle shell-derived calcium carbonate nanoparticles (CSCaCO3NP) are natural biogenic inorganic material that is used in drug delivery mainly as a bone-remodeling agent as well as a delivery agent for various therapeutics against bone diseases. Curcumin possesses a wide safety margin and yet puzzled with the problem of poor bioavailability due to insolubility. Propounding in vitro and in vivo studies on toxicity assessments of newly synthesized nanoparticles are ongoing to overcome some crucial challenges regarding their safety administration. Nanotoxicology has paved ways for concise test protocols to monitor sequential events with regards to possible toxicity of newly synthesized nanomaterials. The development of nanoparticle with no or less toxic effect has gained tremendous attention. Objective: This study aimed at evaluating the in vitro cytotoxic effect of curcumin-loaded cockle shell-derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) and assessing its biocompatibility on normal cells using standard techniques of WST’s assay. Methods: Standard techniques of WST’s assay was used for the evaluation of the biocompatibility and cytotoxicity. Results: The result showed that CSCaCO3NP and Cur-CSCaCO3NP possess minimal toxicity and high biocompatibility on normal cells even at a higher dose of 500 μg/ml and 40 μg/ml, respectively. Conclusion: CSCaCO3NP can be termed an excellent non-toxic nanocarrier for curcumin delivery. Hence, curcumin loaded cockle shell derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) could further be assessed for various in vivo and in vitro therapeutic applications against various bone- related ailments

Evaluation of in vitro release kinetics and mechanisms of curcumin-loaded cockle shell-derived calcium carbonate nanoparticles

Introduction: Curcumin has remarkable pharmacological activities but remains clinically constrained due to its poor bioavailability as a result of insolubility. This has necessitated the search for natural inorganic materials for curcumin delivery. Cockleshells are external hard materials of marine animals often treated as unwanted wastes, which are excellent sources of calcium carbonate. This study aimed to synthesize cockle shell-derived calcium carbonate (aragonite) nanoparticles (CSCaCO3NP) for delivery of curcumin and to evaluate its kinetic release in vitro. Methods: CSCaCO3NP was synthesized and conjugated with curcumin (Cur-CSCaCO3NP) using a simple top down approach and characterized for its physicochemical properties as a potential curcumin carrier. The in vitro release profile was assessed using the dialysis bag membrane method. The release data were fitted to Korsmeyer-Peppas, Zero order, and Higuchi models to evaluate the mechanism(s) of the release pattern. Results: A spherical shaped CSCaCO3NP with a surface area of 14.48+/-0.1 m2/g, with mean diameter size of 21.38+/-2.7 nm and zeta potential of -18.7 mV, was synthesized and found to have high loading content and encapsulation efficiency. The FT-IR and XRD revealed fewer observable changes on the peaks after conjugation. The profile of the in vitro kinetic release demonstrated a sustained release, and which was best fitted to the Higuchi equation model. Conclusion: The results of this study showed the capacity of the synthesized CSCaCO3NP to encapsulate curcumin efficiently with a stable release in vitro. This provides insight into and rationale for the potential of CSCaCO3NP for curcumin delivery. Therefore, CSCaCO3NP holds great prospects in the preclinical framework for enhancing curcumin efficacy in oral therapeutic applications

Curcumin-loaded cockle shell-derived calcium carbonate nanoparticles ameliorates lead-induced neurotoxicity in rats via attenuation of oxidative stress

A substantial global health burden is associated with neurotoxicity caused by lead (Pb) exposure and the common mechanism of this toxicity is mainly via oxidative damage. Curcumin has remarkable pharmacological activities but 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. This study aimed at investigating the ameliorative effect of curcumin-loaded CSCaCO3NP (Cur-CSCaCO3NP) on lead-induced neurotoxicity in rats. A total of 36 male Sprague–Dawley rats were randomly assigned into five groups. Each group consists of 6 rats apart from the control group which consists of 12 rats. During the 4 weeks induction phase, all rats received a flat dose of 50 mg/kg of lead while the control group received normal saline. The treatment phase lasted for 4 weeks, and all rats received various doses of treatments as follows: group C (Cur 100) received 100 mg/kg of curcumin, group D (Cur-CSCaCO3NP 50) received 50 mg/kg of Cur-CSCaCO3NP, and group E (Cur-CSCaCO3NP 100) received 100 mg/kg of Cur-CSCaCO3NP. The motor function test was carried out using the horizontal bar method. The cerebral and cerebellar oxidative biomarker levels were estimated using ELISA and enzyme assay kits. Lead-administered rats revealed a significant decrease in motor scores and SOD activities with a resultant increase in MDA levels. Furthermore, marked cellular death of the cerebral and cerebellar cortex was observed. Conversely, treatment with Cur-CSCaCO3NP demonstrated enhanced ameliorative effects when compared with free curcumin treatment by significantly reversing the aforementioned alterations caused by lead. Thus, CSCaCO3NP enhanced the efficacy of curcumin by ameliorating the lead-induced neurotoxicity via enhanced attenuation of oxidative stress

Estimation of body height from spinal length measurements using post-mortem computed tomographic images

Introduction: Post-mortem computed tomography (PMCT) provides information that helps in the determination of the cause of death and corpse identification of disaster victims. One of the methods for corpse identification includes assessment of the body stature. There is a lack of post-mortem imaging studies that focus on the anthropometric assessment of corpses. Our aim was to identify the relationship between cadaveric spine length and autopsy length (AL) among and autopsy length (AL) among a Malaysian population and derive a regression formula for the estimation of corpse body height using PMCT. Materials and Methods: We retrospectively assessed 107 cadavers that had undergone conventional autopsy and PMCT. We made 5 measurements from the PMCT that included cervical length (CL), thoracic length (TL), lumbosacral length (LS), total column length of the spine, excluding the sacrum and coccyx (TCL), and ellipse line measurement of the whole spine, excluding the sacrum and coccyx (EL). We compared these anthropometric PMCT measurements with AL and correlated them using linear regression analysis. Results: The results showed a significant linear relationship existed between TL and LS with AL, which was higher in comparison with the other parameters than the rest of the spine parameters. The linear regression formula derived was: 48.163 + 2.458 (TL) + 2.246 (LS). Conclusions: The linear regression formula derived from PMCT spine length parameters particularly thoracic and lumbar spine gave a finer correlation with autopsy body length and can be used for accurate estimation of cadaveric height. To the best of our knowledge, this is the first ever linear regression formula for cadaveric height assessment using only post mortem CT spine length measurements

A mini literature review on the application of susceptibility weighted imaging in neuroradiology

Objectives: Susceptibility-weighted imaging (SWI) is a recent and robust advancement in magnetic resonance imaging (MRI) technique that exploits the magnetic susceptibility differences of several tissues such as calcification, deoxygenated blood, and blood products iron. This study aims to highlight the principle and clinical application of SWI in different brain pathologies such as traumatic brain injury, arterial stroke, neurodegenerative disease, and brain tumor. Key findings: SWI is continuously employed in the differential diagnosis of numerous neurological disorders, these advancements in SWI made it an integral part of brain MRI protocol routine in evaluating various neurological diseases such as neurodegenerative and neurovascular diseases. Conclusion: SWI provides an exceptional technique that offers valuable information on neurological disorders as well as cerebral diamagnetic and paramagnetic substances. Implication for practice: The advent of SWI has enormously improved numerous applications in research and clinical neuroradiology such as the detection and assessment of hemorrhage, TBI, and neurodegenerative disease. SWI is a very useful alternative imaging tool in the management of stroke patients, via the facilitation and differentiation of calcium from a brain hemorrhage