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1.
Int J Nanomedicine ; 13: 2349-2363, 2018.
Article in English | MEDLINE | ID: mdl-29713166

ABSTRACT

INTRODUCTION: One of the main issues in the medical field and clinical practice is the development of novel and effective treatments against infections caused by antibiotic-resistant bacteria. One avenue that has been approached to develop effective antimicrobials is the use of silver nanoparticles (Ag-NPs), since they have been found to exhibit an efficient and wide spectrum of antimicrobial properties. Among the main drawbacks of using Ag-NPs are their potential cytotoxicity against eukaryotic cells and the latent environmental toxicity of their synthesis methods. Therefore, diverse green synthesis methods, which involve the use of environmentally friendly plant extracts as reductive and capping agents, have become attractive to synthesize Ag-NPs that exhibit antimicrobial effects against resistant bacteria at concentrations below toxicity thresholds for eukaryotic cells. PURPOSE: In this study, we report a green one-pot synthesis method that uses Acacia rigidula extract as a reducing and capping agent, to produce Ag-NPs with applications as therapeutic agents to treat infections in vivo. MATERIALS AND METHODS: The Ag-NPs were characterized using transmission electron microscopy (TEM), high-resolution TEM, selected area electron diffraction, energy-dispersive spectroscopy, ultraviolet-visible, and Fourier transform infrared. RESULTS: We show that Ag-NPs are spherical with a narrow size distribution. The Ag-NPs show antimicrobial activities in vitro against Gram-negative (Escherichia coli, Pseudomonas aeruginosa, and a clinical multidrug-resistant strain of P. aeruginosa) and Gram-positive (Bacillus subtilis) bacteria. Moreover, antimicrobial effects of the Ag-NPs, against a resistant P. aeruginosa clinical strain, were tested in a murine skin infection model. The results demonstrate that the Ag-NPs reported in this work are capable of eradicating pathogenic resistant bacteria in an infection in vivo. In addition, skin, liver, and kidney damage profiles were monitored in the murine infection model, and the results demonstrate that Ag-NPs can be used safely as therapeutic agents in animal models. CONCLUSION: Together, these results suggest the potential use of Ag-NPs, synthesized by green chemistry methods, as therapeutic agents against infections caused by resistant and nonresistant strains.


Subject(s)
Acacia/chemistry , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/pharmacology , Metal Nanoparticles/chemistry , Silver/pharmacology , Animals , Anti-Infective Agents/chemistry , Bacillus subtilis/drug effects , Drug Resistance, Multiple, Bacterial/drug effects , Escherichia coli/drug effects , Female , Green Chemistry Technology/methods , Microbial Sensitivity Tests , Microscopy, Electron, Transmission , Plant Extracts/chemistry , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/drug effects , Rats, Wistar , Silver/chemistry , Spectrometry, X-Ray Emission , Spectroscopy, Fourier Transform Infrared
2.
Exp Toxicol Pathol ; 69(7): 430-434, 2017 Sep 05.
Article in English | MEDLINE | ID: mdl-28416145

ABSTRACT

Gingko biloba leaves have been used as herbal medicine in China for 5000 years, and the standardized leaf extract (GB-STE) has some beneficial effects in the treatment of age-related, cardiovascular, and neurological diseases. The aim of this study was to investigate the renoprotective effects of the Gingko biloba extract (GbE) against the toxicity of a single and relatively low dose of carbon tetrachloride (CCl4). In male adult Wistar rats, we determined the urine flux, the concentration of total proteins in urine, the concentration of glucose in urine, and the concentration of malondialdehyde (MDA) in renal cortex as well as two markers of renal function (clearance of inulin and p-aminohippurate); we also compared the histological lesions caused by CCl4. Carbon tetrachloride increased the urinary concentration of total proteins, and the renal concentration of MDA; however, it did not modify the urine flux, urinary concentration of glucose, nor the inuline or the p-aminohipurate clearances. Morphologically, CCl4 generated some tubular damage that was more intense in the inner cortex of kidneys. The GbE extract counteracted the effects of CCl4 on the concentration of total proteins in urine, the concentration of renal MDA, and the renal histological changes. In conclusion the main toxic effects produced by CCl4 were prevented by the GbE, probably due to their antioxidant properties and the inhibition of the main P450 isoenzyme (CYP2E1) that metabolize CCl4.


Subject(s)
Antioxidants/pharmacology , Carbon Tetrachloride/toxicity , Kidney/drug effects , Plant Extracts/pharmacology , Animals , Ginkgo biloba , Male , Rats , Rats, Wistar
3.
Hum Exp Toxicol ; 30(3): 209-16, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20571138

ABSTRACT

Functional and morphological alterations were generated by p.o. (per os) administration of a single oral dose of carbon tetrachloride (CCl(4); 0.125 mL/kg b.w., equivalent to 293 mg/kg) to adult male Wistar rats. CCl(4) significantly increased (p < 0.05) the serum activities of alanine aminotransferase (ALT; 7478 ± 1044%) and aspartate aminotransferase (AST; 6964 ± 833%), compared to control rats; CCl(4) also significantly decreased serum concentration of albumin (23 ± 5.5%) and increased the concentration of malondialhdeyde (MDA) in liver (300 ± 33%). Furthermore, CCl(4) down-regulated the mRNA steady-state level of tumor necrosis factor a(TNF-a). CCl(4) produced necrosis in the central lobe area, extended to the periphery, nuclear alterations (pycnosis, karyolysis and karyorrhexis), and cytoplasmic acidophilia. The pretreatment with 4 mg/kg (p.o.) of Ginkgo biloba extract (GbE), for 5 days, prevented most of the damage caused by CCl(4): significantly decreased the serum activities of ALT and AST (54 and 65%, respectively), compared to CCl(4)-treated rats; GbE partially prevented the increase of liver MDA (55 ± 14%) and the decrease of albumin concentration to 12 ± 0.2%. This pretreatment prevented the down-regulation of TNF-a and up-regulated the interleukine 6 (IL-6) mRNA steady-state level. Moreover, the GbE reduced the amount of necrotic areas in the central lobe area, compared to CCl(4)-treated rats.


Subject(s)
Carbon Tetrachloride/toxicity , Chemical and Drug Induced Liver Injury/prevention & control , Ginkgo biloba/chemistry , Plant Extracts/pharmacology , Animals , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/metabolism , Gene Expression Regulation/drug effects , Interleukin-6/metabolism , Male , Malondialdehyde , Plant Extracts/chemistry , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar , Serum Albumin/metabolism , Transaminases/blood , Tumor Necrosis Factor-alpha/metabolism
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