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

Abubakar K, Muhammad Mailafiya M, Danmaigoro A, Musa Chiroma S, Abdul Rahim EB, Abu Bakar Zakaria MZ

Biomolecules, 2019 09 06;9(9).
PMID: 31489882 DOI: 10.3390/biom9090453

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.
Fulltext Modified methods of nanoparticles synthesis in pH-sensitive nano-carriers production for doxorubicin delivery on MCF-7 breast cancer cell line

Hamidu A, Mokrish A, Mansor R, Razak ISA, Danmaigoro A, Jaji AZ, et al.

Int J Nanomedicine, 2019;14:3615-3627.
PMID: 31190815 DOI: 10.2147/IJN.S190830

Purpose: Modified top-down procedure was successfully employed in the synthesis of aragonite nanoparticles (NPs) from cheaply available natural seawater cockle shells. This was with the aim of developing a pH-sensitive nano-carrier for effective delivery of doxorubicin (DOX) on MCF-7 breast cancer cell line. Methods: The shells were cleaned with banana pelts, ground using a mortar and pestle, and stirred vigorously on a rotary pulverizing blending machine in dodecyl dimethyl betane solution. This simple procedure avoids the use of stringent temperatures and unsafe chemicals associated with NP production. The synthesized NPs were loaded with DOX to form DOX-NPs. The free and DOX-loaded NPs were characterized for physicochemical properties using field emission scanning electron microscopy, transmission electron microscopy, zeta potential analysis, Fourier transform infrared spectroscopy, and X-ray diffraction. The release profile, cytotoxicity, and cell uptake were evaluated. Results: NPs had an average diameter of 35.50 nm, 19.3% loading content, 97% encapsulation efficiency, and a surface potential and intensity of 19.1±3.9 mV and 100%, respectively. A slow and sustained pH-specific controlled discharge profile of DOX from DOX-NPs was observed, clearly showing apoptosis/necrosis induced by DOX-NPs through endocytosis. The DOX-NPs had IC50 values 1.829, 0.902, and 1.0377 µg/mL at 24, 48, and 72 hrs, while those of DOX alone were 0.475, 0.2483, and 0.0723 µg/mL, respectively. However, even at higher concentration, no apparent toxicity was observed with the NPs, revealing their compatibility with MCF-7 cells with a viability of 92%. Conclusions: The modified method of NPs synthesis suggests the tremendous potential of the NPs as pH-sensitive nano-carriers in cancer management because of their pH targeting ability toward cancerous cells.
Fulltext Toxicity and Safety Evaluation of Doxorubicin-Loaded Cockleshell-Derived Calcium Carbonate Nanoparticle in Dogs

Danmaigoro A, Selvarajah GT, Mohd Noor MH, Mahmud R, Abu Bakar MZ

Adv Pharmacol Sci, 2018;2018:4848602.
PMID: 30079088 DOI: 10.1155/2018/4848602

Doxorubicin (DOX) is a potent anticancer agent with cytotoxic effects which limit its clinical usage. This effect is due to its nonselective nature causing injury to the cells as a result of reactive free oxygen radical's release. Cockleshell-derived calcium carbonate nanoparticle (CS-CaCO3NP) is a pH-responsive carrier with targeted delivery potentials. This study aimed at evaluating the toxicity effects of repeated dose administration of DOX-loaded CS-CaCO3NP in healthy dogs. Fifteen dogs with an average body weight of 15 kg were randomized equally into 5 groups. Dogs were subjected to 5 doses at every 3-week interval with (i) normal saline, (ii) DOX, 30 mg/m2, and the experimental groups: CS-CaCO3NP-DOX at (iii) high dose, 50 mg/m2, (iv) clinical dose, 30 mg/m2, and (v) low dose, 20 mg/m2. Radiographs, electrocardiography, and blood samples were collected before every treatment for haematology, serum biochemistry, and cardiac injury assessment. Heart and kidney tissues were harvested after euthanasia for histological and ultrastructural evaluation. The cumulative dose of DOX 150 mg/m2 over 15 weeks revealed significant effects on body weight, blood cells, functional enzymes, and cardiac injury biomarkers with alterations in electrocardiogram, myocardium, and renal tissue morphology. However, the dogs given CS-CaCO3NP-DOX 150 mg/m2 and below did not show any significant change in toxicity biomarker as compared to those given normal saline. The study confirmed the safety of repeated dose administration of CS-CaCO3NP-DOX (30 mg/m2) for 5 cycles in dogs. This finding offers opportunity to dogs with cancer that might require long-term administration of DOX without adverse effects.
Gut health and serum growth hormone levels of broiler chickens fed dietary chitin and chitosan from cricket and shrimp

Ibitoye EB, Lokman IH, Hezmee MNM, Goh YM, Zuki ABZ, Jimoh AA, et al.

Poult Sci, 2019 Feb 01;98(2):745-752.
PMID: 30265345 DOI: 10.3382/ps/pey419

Growth hormones (GH) alone does not explain the growth rate in the chicken as growth in an animal is multi-factorial. Normal morphology of the intestinal villus and crypt, with adequate regulation of intestinal nutrient transporters, is essential to a healthy gut. Nutrition plays a significant role in gut health management, but information on the effect of dietary chitin and chitosan on gut morphology, gene expression of nutrient transporter, and serum levels of GH in broiler chickens is scanty. Thus, this study aimed at evaluating the comparative effect of dietary chitin and chitosan from cricket and shrimp on the small intestinal morphology, relative gene expression of intestinal nutrient transporters and serum level of GH in the broiler. A total of 150 day-old male Cobb500 broiler chicks were randomly allotted to one of the five treatment groups (n = 30). Treatment 1 was fed basal diet only, treatments 2 to 5 were fed a basal diet with 0.5 g cricket chitin, cricket chitosan, shrimp chitin, and shrimp chitosan, respectively, per kg diet. At days 21 and 42, duodenal and jejunal samples were assessed for structural morphology and jejunum for the relative gene expression of PepT1, EAAT3, SGLT1, and SGLT5 using quantitative real-time PCR. Results bared that dietary cricket chitosan and shrimp chitosan significantly (P < 0.05) improved jejunal villus height and reduced crypt depth without improving the body weight (BW). The gut morphology of birds under cricket chitin was poor and significantly (P < 0.05) different from other treated groups. Both the dietary chitin and chitosan at day 21 and only dietary chitosan at day 42 significantly (P < 0.05) down-regulated the relative mRNA expression of PepT1, EAAT3, SGLT1, and SGLT5 of broiler chickens. Treated groups differ non-significantly at both phases, while cricket chitin numerically increased the relative expression of PepT1, EAAT3, and SGLT1. Therefore, the potential of cricket chitin to improve BW and to up-regulate nutrient transporters is worthy of further exploration.
Ameliorative effect of curcumin on lead-induced hematological and hepatorenal toxicity in a rat model

Abubakar K, Mailafiya MM, Chiroma SM, Danmaigoro A, Zyoud TYT, Abdul Rahim E, et al.

J Biochem Mol Toxicol, 2020 Jun;34(6):e22483.
PMID: 32125074 DOI: 10.1002/jbt.22483

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

Mailafiya MM, Abubakar K, Chiroma SM, Danmaigoro A, Rahim EBA, Mohd Moklas MA, et al.

Saudi J Biol Sci, 2020 Jun;27(6):1538-1552.
PMID: 32489292 DOI: 10.1016/j.sjbs.2020.03.009

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

Mailafiya MM, Abubakar K, Chiroma SM, Danmaigoro A, Zyoud TYT, Rahim EBA, et al.

Food Sci Nutr, 2023 May;11(5):2211-2231.
PMID: 37181299 DOI: 10.1002/fsn3.3096

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.
Fulltext LC-MS/MS Proteomic Study of MCF-7 Cell Treated with Dox and Dox-Loaded Calcium Carbonate Nanoparticles Revealed Changes in Proteins Related to Glycolysis, Actin Signalling, and Energy Metabolism

Ahmed H, Ajat M, Mahmood RI, Mansor R, Razak ISA, Al-Obaidi JR, et al.

Biology (Basel), 2021 Sep 13;10(9).
PMID: 34571787 DOI: 10.3390/biology10090909

One of the most prevalent death causes among women worldwide is breast cancer. This study aimed to characterise and differentiate the proteomics profiles of breast cancer cell lines treated with Doxorubicin (DOX) and Doxorubicin-CaCO3-nanoparticles (DOX-Ar-CC-NPs). This study determines the therapeutic potential of doxorubicin-loaded aragonite CaCO3 nanoparticles using a Liquid Chromatography/Mass Spectrometry analysis. In total, 334 proteins were expressed in DOX-Ar-CC-NPs treated cells, while DOX treatment expressed only 54 proteins. Out of the 334 proteins expressed in DOX-CC-NPs treated cells, only 36 proteins showed changes in abundance, while in DOX treated cells, only 7 out of 54 proteins were differentially expressed. Most of the 30 identified proteins that are differentially expressed in DOX-CC-NPs treated cells are key enzymes that have an important role in the metabolism of carbohydrates as well as energy, including: pyruvate kinase, ATP synthase, enolase, glyceraldehyde-3-phosphate dehydrogenase, mitochondrial ADP/ATP carrier, and trypsin. Other identified proteins are structural proteins which included; Keratin, α- and β-tubulin, actin, and actinin. Additionally, one of the heat shock proteins was identified, which is Hsp90; other proteins include Annexins and Human epididymis protein 4. While the proteins identified in DOX-treated cells were tubulin alpha-1B chain and a beta chain, actin cytoplasmic 1, annexin A2, IF rod domain-containing protein, and 78 kDa glucose-regulated protein. Bioinformatics analysis revealed the predicted canonical pathways linking the signalling of the actin cytoskeleton, ILK, VEGF, BAG2, integrin and paxillin, as well as glycolysis. This research indicates that proteomic analysis is an effective technique for proteins expression associated with chemotherapy drugs on cancer tumours; this method provides the opportunity to identify treatment targets for MCF-7 cancer cells, and a liquid chromatography-mass spectrometry (LC-MS/MS) system allowed the detection of a larger number of proteins than 2-DE gel analysis, as well as proteins with maximum pIs and high molecular weight.