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1.
Colloids Surf B Biointerfaces ; 206: 111935, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34252691

RESUMO

Silver nanoparticles (AgNPs) could be employed in the combat against COVID-19, yet are associated with toxicities. In this study, biogenic and biocompatible AgNPs using the agro-waste, non-edible Hibiscus sabdariffa stem were synthesized. Under optimized reaction conditions, synthesized green AgNPs were crystalline, face cubic centered, spherical with a diameter of around 17 nm and a surface charge of -20 mV. Their murine lethal dose 50 (LD50) was 4 folds higher than the chemical AgNPs. Furthermore, they were more murine hepato- and nephro-tolerated than chemical counterparts due to activation of Nrf-2 and HO-1 pathway. They exerted an apoptotic anti-ovarian cancer activity with IC50 value 6 times more than the normal cell line. Being functionalized with polydopamine and conjugated to either moxifloxacin or gatifloxacin, the conjugates exerted an augmented antibiofilm activity against Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii biofilms that was significantly higher than antibiotic alone or functionalized AgNPs suggesting a synergistic activity. In conclusion, this study introduced a facile one-pot synthesis of biogenic and biocompatible AgNPs with preferential anti-cancer activity and could be utilized as antibiotic delivery system for a successful eradication of Gram-negative biofilms.


Assuntos
Antibacterianos , Nanopartículas Metálicas , Prata , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Química Verde , Hibiscus , Indóis , Camundongos , Testes de Sensibilidade Microbiana , Polímeros , Prata/farmacologia
2.
Int J Biol Macromol ; 185: 134-152, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34147524

RESUMO

This study was designed to present a new quercetin encapsulated chitosan functionalized copper oxide nanoparticle (CuO-ChNPs-Q) and assessed its anti-breast cancer activity both in vitro and in vivo. The CuO-ChNPs-Q may act as anti-proliferating agent against DMBA-induced mammary carcinoma in female rats. The CuONPs was functionalized with chitosan then quercetin was conjugated with them producing CuO-ChNPs-Q, then characterized. The in vitro anti-proliferating activity of the CuO-ChNPs-Q was evaluated against three human cell line. Then, the anti-breast cancer effect of the CuO-ChNPs-Q was assessed against DMBA-induction compared to both CuONPs and Q in female rat model. The in vitro results proved the potent anticancer activity of the CuO-ChNPs-Q compared to CuONPs and quercetin. The in vivo data showed significant reduction in breast tumors of DMBA-induced rats treated with CuO-ChNPs-Q compared to CuONPs and Q. The CuO-ChNPs-Q treatment had induced apoptosis via increased p53 gene, arrested the cell-cycle, and increased both cytochrome c and caspase-3 levels leading to mammary carcinoma cell death. Also, the CuO-ChNPs-Q treatment had suppressed the PCNA gene which decreased the proliferation of the mammary carcinoma cells. In conclusion, the CuO-ChNPs-Q might be a promising chemotherapeutic agent for treatment of breast cancer with a minimal toxicity on vital organs.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Quitosana/química , Cobre/química , Quercetina/administração & dosagem , Proteína Supressora de Tumor p53/metabolismo , 9,10-Dimetil-1,2-benzantraceno/efeitos adversos , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/metabolismo , Células CACO-2 , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Células MCF-7 , Nanopartículas Metálicas , Antígeno Nuclear de Célula em Proliferação/metabolismo , Quercetina/química , Quercetina/farmacologia , Ratos , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Molecules ; 25(18)2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32962014

RESUMO

New anticancer ruthenium(II/III) complexes [RuCl2(DMSO)2(Hapbim)] (1) and [RuCl3(DMSO) (Hapbim)] (2) (Hapbim = 2-aminophenyl benzimidazole) have been synthesized and characterized, and their chemotherapeutic potential evaluated. The interaction of the compounds with DNA was studied by both UV-Visible and fluorescence spectroscopies, revealing intercalation of both the Hapbim ligand and the Ru complexes. The in vitro cytotoxicity of the compounds was tested on human breast cancer (MCF7), human colorectal cancer (Caco2), and normal human liver cell lines (THLE-2), with compound (2) the most potent against cancer cells. The cytotoxic effect of (2) is shown to correlate with the ability of the Ru(III) complex to induce apoptosis and to cause cell-cycle arrest in the G2/M phase. Notably, both compounds were inactive in the noncancerous cell line. The anticancer effect of (2) has also been studied in an EAC (Ehrlich Ascites Carcinoma) mouse model. Significantly, the activity of the complex was more pronounced in vivo, with removal of the cancer burden at doses that resulted in only low levels of hepatotoxicity and nephrotoxicity. An apoptosis mechanism was determined by the observation of increased Bax and caspase 3 and decreased Bcl2 expression. Furthermore, (2) decreased oxidative stress and increased the levels of antioxidant enzymes, especially SOD, suggesting the enhancement of normal cell repair. Overall, compound (2) shows great potential as a chemotherapeutic candidate, with promising activity and low levels of side effects.


Assuntos
Antineoplásicos/química , Complexos de Coordenação/química , Rutênio/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Benzimidazóis/química , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Dimetil Sulfóxido/química , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Regulação para Cima/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
4.
Int J Biol Macromol ; 160: 1230-1241, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32474075

RESUMO

This study aimed to present a new heart of P. dactylifera (HP) extract loaded chitosan nanoparticles and estimate its anticancer, antimicrobial, antioxidant activity and free radical scavenger effect (in vitro). This nano-supplement may prevent doxorubicin cardiotoxicity and nephrotoxicity in rat model. The HP extract was loaded on chitosan nanoparticles producing HP-ChNPs, then characterized. The antioxidant properties of the HP-ChNPs was assessed in vitro. The antibacterial activity against three-gram positive bacteria and two gram-negative bacteria were done. The in vitro studies of cytotoxicity against MCF7, CaCo3, and Hela cell lines were also evaluated. Then, the protective effect of the HP-ChNPs (2 mg/kg, IP) was evaluated against doxorubicin induce organ toxicity in a rat model. The in vitro studies revealed the antibacterial, anticancer and antioxidant activities of the HP-ChNPs. The in vivo study demonstrates reduction of heart and kidney apoptosis with increased programmed cell death protein-1 (PD-1); as the major anticancer drug (doxorubicin) pathway is to release free radicals with decreased PD-1 levels and induction of apoptosis. In conclusion, the HP-ChNPs, in a very small dose, might be a promising supplement to avoid doxorubicin toxicity with improvment the antioxidant enzymes without affecting its anticancer activity.


Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Quitosana/análogos & derivados , Nanopartículas/química , Extratos Vegetais/farmacologia , Animais , Anti-Infecciosos/administração & dosagem , Antineoplásicos/administração & dosagem , Antioxidantes/administração & dosagem , Apoptose/efeitos dos fármacos , Doxorrubicina/toxicidade , Células HeLa , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Células MCF-7 , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Oxidantes/toxicidade , Phoeniceae/química , Extratos Vegetais/administração & dosagem , Ratos , Ratos Sprague-Dawley
5.
Food Chem Toxicol ; 135: 111045, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31830546

RESUMO

Cardiotoxicity and nephrotoxicity due to the abnormal production of free radicals have been observed in patients treated with the anticancer antibiotic adriamycin (ADR). The aim of the present study was to evaluate the role of the heart of palm extract in preventing oxidative stress, cardiotoxicity and nephrotoxicity induced by ADR. In this work, an aqueous ethanolic extract of the heart of the Phoenix dactylifera tree (HP) was investigated. The polyphenol content was evaluated by gas chromatography-mass spectrometry (GC-MS) and High-performance liquid chromatography (HPLC). The protective effect of the HP-extract (250 and 500 mg/kg, p.o.) was evaluated along with ADR administration (cumulative dose 15 mg/kg, IP) in rats. The HP-extract (500 mg/kg) treated group showed significant reductions in cardiotoxicity and nephrotoxicity serum markers, apoptotic percentage, and caspase-3 and cyclooxygenase-2 level, with an improvement in antioxidant enzymes in both heart and kidney homogenate, compared with the ADR-induction group. The cardiac and kidney programmed cell death protein-1 (PD-1) was increased in high dose HP-extract treated rats after being inhibited by ADR administration. In conclusion, the HP-extract might be a promising food supplement for preventing the cardiotoxicity and nephrotoxicity induced by ADR administration.


Assuntos
Apoptose/efeitos dos fármacos , Doxorrubicina/toxicidade , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Phoeniceae/química , Extratos Vegetais/farmacologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Animais , Relação Dose-Resposta a Droga , Masculino , Extratos Vegetais/química , Polifenóis/metabolismo , Ratos , Ratos Sprague-Dawley
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