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1.
BMC Pharmacol Toxicol ; 24(1): 11, 2023 02 23.
Article in English | MEDLINE | ID: mdl-36823675

ABSTRACT

Neurotoxicity is a severe side effect of platinum compounds used for cancer chemotherapy such as Cisplatin. This neurotoxicity leads to severe cognitive and nervous dysfunction, therefore, limiting the dose of Cisplatin and compromising the treatment protocol.The present study investigates the neuroprotective effect of Sea Urchins which is a marine animal known for its rich bioactive compounds. Male Sprague Dawley rats received Cisplatin (2 mg/kg body weight) for 4 weeks, two times per week, followed by Sea Urchin extracts (50 and 100 mg/kg body weight) twice weekly for 4 weeks.Results show that rats treated with Urchin's extracts showed a significant improvement in the thermal (heat and cold) sensitivity compared to untreated rats. Liver enzymes Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) and Urea levels were also significantly decreased back to normal following treatment with sea urchin extracts. Brain tissue oxidative stress marker Nitric oxide (NO) and lipid peroxidation marker Malondialdehyde (MDA) increased significantly in the cisplatin-treated rats while the reduced glutathione levels (GSH) and catalase activity (CAT) showed a significant decrease. Treatment with sea Urchin extracts reversed these changes.Histological and immunohistochemical examination of the cerebral cortex reveled degenerative changes such as karyopyknosis and shrunken necrotic ghost like neurons in the cisplatin treated groups. There was also strong positive Glial fibrillary acidic protein (GFAP) reactivity and a negative B-cell leukemia/lymphoma 2 protein (Bcl2) reaction in most apparent neurons, indicating strong apoptotic changes. Treatment with Urchin extracts reversed these changes. Quantification of cerebral cortex neurons also revealed the strong effect of the extracts. Cisplatin treated groups showed 3708 cells/ mm3 compared to 8091 cells/mm3 in the normal rats. Extract treatment increased the neuronal numbers to almost normal levels. Quantification of the Immuno-histochemical expression of GFAP showed an increase by 10-folds after cisplatin administration. A remarkable decline from the cisplatin group was seen in the extract treated groups.In Conclusion, Sea Urchins extracts possess a strong neuroprotective activity and could provide a novel therapeutic method to prevent Cisplatin-induced neurotoxicity.


Subject(s)
Biological Products , Cisplatin , Neuroprotective Agents , Animals , Male , Rats , Antioxidants/pharmacology , Body Weight , Cisplatin/adverse effects , Glutathione/metabolism , Lipid Peroxidation , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Oxidative Stress , Rats, Sprague-Dawley , Sea Urchins/chemistry , Biological Products/pharmacology
2.
ACS Appl Bio Mater ; 5(8): 3678-3694, 2022 08 15.
Article in English | MEDLINE | ID: mdl-35820172

ABSTRACT

We report the development and evaluation of a series of well-designed single-dose extracellular matrix (ECM)-mimicking nanofibers (NFs)-reinforced hydrogel (HG)-based skin substitute for wound healing. The HG matrix of the proposed skin substitute is composed of gelatin (GE) and sodium alginate (SA), and incorporates hyaluronic acid (HA) as a key component of the natural ECM, as well as the antimicrobial Punica granatum extract (PE). This HG nanocomposite was cross-linked by the biocompatible N-(3-(dimethylamino)propyl)-N'-ethylcarbodiimide hydrochloride (EDC) cross-linker, and was reinforced with fragmented trans-ferulic acid (FA)-loaded cellulose acetate/polycaprolactone (PCL/CA) NFs. The NFs were obtained via wet electrospinning into a poly(vinyl alcohol) (PVA) coagulating solution to closely resemble the porous structure of the ECM fibers, which facilitates cell migration, attachment, and proliferation. The proposed design of the skin substitute allows adjustable mechanical characteristics and outstanding physical properties (swelling and biodegradability), as well as an excellent porous microstructure. The developed skin substitutes were characterized using Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and electron microscopy. In addition, the biodegradability, biocompatibility, bioactivity, mechanical, and in vitro drug release characteristics were investigated. Moreover, an in vivo excisional full-thickness defect model was conducted to assess skin regeneration and healing effectiveness. The average diameters of the plain and FA-loaded NFs are 210 ± 12 nm and 452 ± 25 nm, respectively. The developed ECM-mimicking skin substitutes demonstrated good antibacterial activity, free-radical scavenging activity, cytocompatibility, porosity, water absorption ability, and good biodegradability. In vivo application of the ECM-mimicking skin substitutes revealed their excellent wound-healing activity and their suitability for single-dose treatment of deep wounds with reducing the wound diameter to 0.95 mm after 15 days of treatment. Moreover, the histological investigation of the wound area demonstrated that the applied skin substitutes have not only enhanced the wound healing progress, but also can participate in improving the quality of the regenerated skin in the treated area via facilitating collagen fibers regeneration and deposition.


Subject(s)
Nanocomposites , Nanofibers , Skin, Artificial , Alginates/chemistry , Anti-Bacterial Agents , Gelatin , Nanocomposites/therapeutic use , Nanofibers/therapeutic use
3.
J Cosmet Dermatol ; 20(12): 4011-4016, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34525492

ABSTRACT

BACKGROUND: Melasma, also known as chloasma or mask of pregnancy, is a common, acquired, hyperpigmentary disorder usually affecting females. Tranexamic acid (TA), a derivative of amino acid lysine, has shown promising results over the past few years when used along with other therapies and when used as a stand-alone therapy. AIM OF THE WORK: In this study, we aimed to evaluate and compare the effectiveness of topically applied tranexamic acid after microneedling versus topically applied hydroquinone (HQ) 4% alone in patients with melasma. PATIENTS AND METHODS: Fifty selected patients were divided randomly according to the random number allocation method into two groups (25 patients each) of A (topical 4% hydroquinone, nightly application) and B (microneedling + topical 4% TA, every other week). RESULTS: After eight weeks of treatment, the mean modified MASI score of the HQ treated side changed from 6.604 ± 4.02 to 3.032 ± 1.19 with a mean decrease percentage of 54.8% ± 19.4%. This reduction in modified MASI score was found to be statistically significant, (p < 0.001). MASI score of group B (TA +microneedling) changed from 6.348 ± 3.84 to 3.712 ± 1.19 with mean decrease percentage of 57.4% ± 23.4% which was also statistically significant, (p < 0.001). CONCLUSION: We demonstrated safety and efficacy of both used modalities and with minimal side effects. Topical HQ application achieved minimal non-significant higher satisfactory results among raters and subjects.


Subject(s)
Melanosis , Tranexamic Acid , Female , Humans , Hydroquinones , Melanosis/drug therapy , Treatment Outcome
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