Ferrocene/ β-cyclodextrin based supramolecular nanogels as theranostic systems

A supramolecular redox responsive nanogel (NG) with the ability to sense cancer cells and loaded with a releasing therapeutic agent was synthesized using hostguest interactions between polyethylene glycol-grafted-β-cyclodextrin and ferrocene boronic acid. Cyclic voltammetry matched with other spectroscopy and microscopy methods provided strong indications regarding host-guest interactions and formation of the NG. Moreover, the biological properties of the NG were evaluated using fluorescence silencing, confocal laser scanning microscopy, and cell toxicity assays. Nanogel with spherical core-shell architecture and 100–200 nm sized nanoparticles showed high encapsulation efficiency for doxorubicin (DOX) and luminol (LU) as therapeutic and sensing agents. High therapeutic and sensing efficiencies were manifested by complete release of DOX and dramatic quenching of LU fluorescence triggered by 0.05 mM H2O2 (as an ROS component). The NGs showed high ROS sensitivity. Taking advantage of a high loading capacity, redox sensitivity, and biocompatibility, the NGs can be used as strong theranostic systems in inflammation-associated diseases

Antioxidant Activity of Glycyrrhiza glabra L. Extract and Protective Effect of its Leaf Extract on Ethanol-Induced Nephrotoxicity in Male Rats

Introduction: Acute alcohol consumption leads to induction of lipid peroxidation in renal tissues, but its chronic consumption has moderate effects on biochemical and histological characteristics of this organ. Antioxidants have protective effects against ethanol-induced oxidative stress and tissue injury. The aim of this study was to assess antioxidant activity of Glycyrrhiza glabra leaf and stem extracts and the protective effect of its leaf extract on ethanol-induced nephrotoxicity.   Materials & methods: Total phenol and flavonoid contents of leaf and stem extracts of G. glabra were measured by Folin Ciocalteu and AlCl3 assays, respectively. Antioxidant activity of both extracts was assessed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. In addition, protective effect of the leaf extract was assessed using biochemical and histological analyses of renal tissues of male Wistar rats, which were divided into four groups including group 1 or control (received 1 ml distilled water daily), group 2 or ethanol group (received 1 ml of 50% ethanol daily), group 3 or ethanol + leaf extract group (received 1 ml of 50% ethanol + 500 mg/kg leaf extract daily), and group 4 (received 500 mg/kg of leaf extract daily). All treatments are performed through intragastric administration. Biochemical and histological analyses were used for the evaluation of nephrotoxicity. For histological study, the samples were stained with Hematoxylin-Eosin and examined by light microscopy. Finally, all the data were analyzed by SPSS (Ver. 20) and grouped by Duncan's Multiple Range Test at P <0.05 level.   Findings: There was no significant difference between total phenol contents of the stem and leaf extracts. However, the stem extract showed a higher total flavonoid content than the leaf extract. Also, both the extracts showed higher antioxidant activities (86-93%) than that of ascorbic acid (71%). Results from biochemical analysis indicated a significant increase in superoxide dismutase (SOD) activity and H2O2 content in the renal tissues of ethanol-treated rats in comparison with other groups; however, there were no significant changes in total protein and malondialdehyde (MDA) contents. Results from histological examination showed that alcohol consumption intensity injured kidney tissues, which was effectively moderated by the studied extract.   Discussion & Conclusions: Results from the present study showed that G. glabra extract has biological activity and can be used in future as a new natural antioxidant in food and drug industries

Effect of Embryonic Cerebrospinal Fluid on Proliferation and Differentiation of Neuroprogenitor Cells

Objective: Embryonic cerebrospinal fluid (e-CSF) has an important role in development of embryonic and adult brain. Proteomic analysis suggests that this fluid has many morphogenes and cytokines that alter in time and space throughout embryonic life. The aim of this study was to evaluate the developmental effect of embryonic CSF on proliferation and differentiation of neuroprogenitor cells in different gestational age.Materials and Methods: In this In this experimental study, we examined the role of e-CSF on proliferation and differentiation of neuroprogenitor cells using neurosphere culture method. Neurospheres size analysis and MTT assay were used to assess cell proliferation after four days in vitro. Glial differentiation study was carried out by immunocytochemistry. Neurospheres size and percentage of glial fibrialy acidic protein (GFAP) positive cells were measured by image analyzer (image J). The data were analyzed by one-way ANOVA, followed by the Tukey’s post hoc test. Data were expressed as mean ± SEM, and differences were considered significant when p<0.05, 0.01 and 0.001.Results: Viability and proliferation of neuro progenitor cells in cultures conditioned with E16 CSF and E18 CSF were significantly increased compare to control group. A dramatic decrease in percentage of GFAP-positive cells was found following the application of CSF from E16 and E18 embryos, but not E20 CSF.Conclusion: Our data suggest that, e-CSF altered proliferation and differentiation of neuro progenitor cells in age dependent manner. E16 and E18 CSF enhanced proliferation and viability of neuro progenitor cells, and inhibited differentiation to glial fate in comparison with control group

Protective effect of Arctium lappa on oxidative stress and nephrotoxicity induced by gentamicin

This study aimed to investigate the protective effect of Arctium lappa (AL) on gentamicin (GM)-induced nephrotoxicity in rats. Twenty-four Wistar rats were divided into four groups including: control group; GM group (intrapritoneal injection, IP, of 100 mg/kg GM B.W.); GM+AL group (received IP injection of 100 mg/kg GM and 500 mg/kg AL orally) and AL group (received 500 mg/kg AL orally). The experimental period lasted for 10 days. Nephrotoxicity was biochemically and histologically evaluated. The concentrations of creatinine, urea, malondialdehyde (MDA), superoxide dismutase (SOD) and peroxide hydrogen (H2O2) in the serum samples were determined. Moreover, histological examinations were performed. The animals treated with gentamicin showed significantly higher serum urea, creatinine, MDA and H2O2 levels and lower SOD activity. However, co-administration of AL produced amelioration in biochemical indices of nephrotoxicity in serum. Histomorphological examination showed necrosis and desquamation of tubular epithelial cells in the renal cortex in animals treated with gentamicin whereas simultaneous administration of AL and GM reduced histological damages. The data obtained suggest that treatment with AL extract can help to reduce gentamicin-induced nephrotoxicity

Oil-In-Water Microemulsion Encapsulation of Antagonist Drugs Prevents Renal Ischemia-Reperfusion Injury in Rats

Developing new therapeutic drugs to prevent ischemia/reperfusion (I/R)-induced renal injuries is highly pursued. Liposomal encapsulation of spironolactone (SP) as a mineralocorticoid antagonist increases dissolution rate, bioavailability and prevents the drug from degradation. In this context, this work develops a new formulation of oil-in-water type microemulsions to enhance the bioavailability of SP. The size of the SP-loaded microemulsion was about 6.0 nm by dynamic light scattering analysis. Briefly, we investigated the effects of nano-encapsulated SP (NESP) on renal oxidative stress, biochemical markers and histopathological changes in a rat model of renal I/R injury. Forty eight male Wistar rats were divided into six groups. Two groups served as control and injury model (I/R). Two groups received “conventional” SP administration (20 mg/kg) and NESP (20 mg/kg), respectively, for two days. The remaining two groups received SP (20 mg/kg) and NESP (20 mg/kg) two days before induction of I/R. At the end of the experiments, serum and kidneys of rats underwent biochemical, molecular and histological examinations. Our results showed that I/R induces renal oxidative stress, abnormal histological features and altered levels of renal biomarkers. Administration of SP in healthy animals did not cause any significant changes in the measured biochemical and histological parameters compared to the control group. However, SP administration in the I/R group caused some corrections in renal injury, although it could not completely restore I/R-induced renal oxidative stress and kidney damage. On the contrary, NESP administration restored kidney oxidative injury via decreasing renal lipid peroxidation and enhancing glutathione, superoxide dismutase and catalase in kidneys of the I/R group. The deviated serum levels of urea, creatinine, total proteins and uric acid were also normalized by NESP administration. Furthermore, NESP protected against renal abnormal histology features induced by I/R. Therefore, NESP has beneficial effects in preventing kidney damage and renal oxidative stress in a rat model of I/R, which deserves further evaluations in the future

Effect of Hydroethanolic Extract of Nigella sativa L. on Skin Wound Healing Process in Diabetic Male Rats.

BACKGROUND: The aim of this study was to investigate the effect of hydroethanolic Nigella sativa L. extract on skin wound healing in diabetic male rats. METHODS: This experimental study was conducted on 49 male Wistar rats weighing 220-250 g divided into 7 groups of 7 each: control (nondiabetic untreated), sham (nondiabetic eucerin-treated), nondiabetic phenytoin (1%)-treated, diabetic untreated, and three diabetic groups treated independently with phenytoin 1%, hydroethanolic N. sativa extracts 20% or 40%. Diabetes was induced with 60 mg/kg streptozosin in one administration. After anesthesia, 2 × 1 cm2 wounds were made on the rats' backs and each group was administered with its own respective treatment until the wounds were healed completely. Tissue specimens were prepared for histological examinations. The areas of the wounds were measured every 3 days. The data were analyzed by ANOVA and Tukey's post-hoc test. RESULTS: The mean duration of wound healing was 27 and 24 days for diabetic untreated and diabetic phenytoin-treated groups, respectively. Wounds were healed completely in nondiabetic untreated, sham, and nondiabetic phenytoin-treated groups on days 23, 24, and 21, respectively. The shortest duration of wound healing was seen in diabetic N. sativa extract (40%)-treated group (15 days) followed by diabetic N. sativa (20%)-treated group (18 days). These two groups were found to have the lowest mean wound area during the study with a significant difference from mean wound area in the controls (P < 0.05). CONCLUSIONS: N. sativa extract significantly promoted wound healing in diabetic rats in comparison with control groups. Although the beneficial mechanism of the promotion of wound healing was not specifically studied, it is believed that the anti-inflammatory and antimicrobial properties of N. sativa would contribute to this enhanced wound healing. KEYWORDS: Diabetes; Nigella sativa L.; rat; skin woun

Effect of Hydroethanolic Extract of Nigella sativa L. on Skin Wound Healing Process in Diabetic Male Rats.

BACKGROUND: The aim of this study was to investigate the effect of hydroethanolic Nigella sativa L. extract on skin wound healing in diabetic male rats. METHODS: This experimental study was conducted on 49 male Wistar rats weighing 220-250 g divided into 7 groups of 7 each: control (nondiabetic untreated), sham (nondiabetic eucerin-treated), nondiabetic phenytoin (1%)-treated, diabetic untreated, and three diabetic groups treated independently with phenytoin 1%, hydroethanolic N. sativa extracts 20% or 40%. Diabetes was induced with 60 mg/kg streptozosin in one administration. After anesthesia, 2 × 1 cm2 wounds were made on the rats' backs and each group was administered with its own respective treatment until the wounds were healed completely. Tissue specimens were prepared for histological examinations. The areas of the wounds were measured every 3 days. The data were analyzed by ANOVA and Tukey's post-hoc test. RESULTS: The mean duration of wound healing was 27 and 24 days for diabetic untreated and diabetic phenytoin-treated groups, respectively. Wounds were healed completely in nondiabetic untreated, sham, and nondiabetic phenytoin-treated groups on days 23, 24, and 21, respectively. The shortest duration of wound healing was seen in diabetic N. sativa extract (40%)-treated group (15 days) followed by diabetic N. sativa (20%)-treated group (18 days). These two groups were found to have the lowest mean wound area during the study with a significant difference from mean wound area in the controls (P < 0.05). CONCLUSIONS: N. sativa extract significantly promoted wound healing in diabetic rats in comparison with control groups. Although the beneficial mechanism of the promotion of wound healing was not specifically studied, it is believed that the anti-inflammatory and antimicrobial properties of N. sativa would contribute to this enhanced wound healing. KEYWORDS: Diabetes; Nigella sativa L.; rat; skin woun

Effect of hydroethanolic extract of Nigella sativa L. on skin wound healing process in diabetic male rats

Background: The aim of this study was to investigate the effect of hydroethanolic Nigella sativa L. extract on skin wound healing in diabetic male rats. Methods: This experimental study was conducted on 49 male Wistar rats weighing 220–250 g divided into 7 groups of 7 each: control (nondiabetic untreated), sham (nondiabetic eucerin-treated), nondiabetic phenytoin (1%)-treated, diabetic untreated, and three diabetic groups treated independently with phenytoin 1%, hydroethanolic N. sativa extracts 20% or 40%. Diabetes was induced with 60 mg/kg streptozosin in one administration. After anesthesia, 2 × 1 cm2 wounds were made on the rats' backs and each group was administered with its own respective treatment until the wounds were healed completely. Tissue specimens were prepared for histological examinations. The areas of the wounds were measured every 3 days. The data were analyzed by ANOVA and Tukey's post-hoc test. Results: The mean duration of wound healing was 27 and 24 days for diabetic untreated and diabetic phenytoin-treated groups, respectively. Wounds were healed completely in nondiabetic untreated, sham, and nondiabetic phenytoin-treated groups on days 23, 24, and 21, respectively. The shortest duration of wound healing was seen in diabetic N. sativa extract (40%)-treated group (15 days) followed by diabetic N. sativa (20%)-treated group (18 days). These two groups were found to have the lowest mean wound area during the study with a significant difference from mean wound area in the controls (P < 0.05). Conclusions: N. sativa extract significantly promoted wound healing in diabetic rats in comparison with control groups. Although the beneficial mechanism of the promotion of wound healing was not specifically studied, it is believed that the anti-inflammatory and antimicrobial properties of N. sativa would contribute to this enhanced wound healing

Ferrocene/ β-cyclodextrin based supramolecular nanogels as theranostic systems

A supramolecular redox responsive nanogel (NG) with the ability to sense cancer cells and loaded with a releasing therapeutic agent was synthesized using hostguest interactions between polyethylene glycol-grafted-β-cyclodextrin and ferrocene boronic acid. Cyclic voltammetry matched with other spectroscopy and microscopy methods provided strong indications regarding host-guest interactions and formation of the NG. Moreover, the biological properties of the NG were evaluated using fluorescence silencing, confocal laser scanning microscopy, and cell toxicity assays. Nanogel with spherical core-shell architecture and 100–200 nm sized nanoparticles showed high encapsulation efficiency for doxorubicin (DOX) and luminol (LU) as therapeutic and sensing agents. High therapeutic and sensing efficiencies were manifested by complete release of DOX and dramatic quenching of LU fluorescence triggered by 0.05 mM H2O2 (as an ROS component). The NGs showed high ROS sensitivity. Taking advantage of a high loading capacity, redox sensitivity, and biocompatibility, the NGs can be used as strong theranostic systems in inflammation-associated diseases