Gold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats

Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2 g/kg p.o. once only. After 24 h of APAP intoxication, animals were treated with three different doses of AuNPs (50 μg/kg, 100 μg/kg, 150 μg/kg) orally or silymarin at a dose of 50 mg/kg p.o., once only. Animals of all the groups were sacrificed after 24 h of last treatment. APAP administered group showed a significant rise in the AST, ALT, SALP, LDH, cholesterol, bilirubin, albumin, urea and creatinine in serum which indicated the hepato-renal damage. A significantly enhanced LPO and a depleted level of GSH were observed in APAP intoxicated rats. Declined activities of SOD and Catalase, after acetaminophen exposure indicated oxidative stress in liver and kidney. The activities of ATPase and glucose-6-Phosphatase were significantly inhibited after APAP administration. AuNPs treatment reversed all variables significantly towards normal level and was found nontoxic. Thus it is concluded that gold nanoparticles played a beneficial role in reducing acetaminophen induced toxicity and can be used in the development of drug against hepatic as well as renal diseases, after further preclinical and clinical studies.     

Fullerenol nanoparticles prevents doxorubicin-induced acute hepatotoxicity in rats

Doxorubicin (DOX), commonly used antineoplastic agent, affects bone marrow, intestinal tract and heart, but it also has some hepatotoxic effects. Main mechanism of its toxicity is the production of free reactive oxygen species. Polyhidroxilated C₆₀ fullerene derivatives, fullerenol nanoparticles (FNP), act as free radical scavengers in in vitro systems. The aim of the study was to investigate potential FNP protective role against DOX-induced hepatotoxicity in rats. Experiments were performed on adult male Wistar rats. Animals were divided into five groups: (1) 0.9% NaCl (control), (2) 100 mg/kg ip FNP, (3) 10 mg/kg DOX iv, (4) 50 mg/kg ip FNP 30 min before 10 mg/kg iv DOX, (5) 100 mg/kg ip FNP 30 min before 10 mg/kg iv DOX. A general health condition, body and liver weight, TBARS level and antioxidative enzyme activity, as well as pathohistological examination of the liver tissue were conducted on days 2 and 14 of the study. FNP, applied alone, did not alter any examinated parameters. However, when used as a pretreatment it significantly increased survival rate, body and liver weight, and decreased TBARS level, antioxidative enzyme activity and hepatic damage score in DOX-treated rats. FNP administered at a dose of 100 mg/kg significantly attenuated effects of doxorubicin administered in a single high dose in rats, concerning general condition, body and liver weight, lipid peroxidation level and antioxidative enzyme activity as well as structural alterations of the hepatic tissue.     

Inhibition of the growth of human dermatophytic pathogens by selected australian and asian plants traditionally used to treat fungal infections

ObjectiveSyzygium australe (H.L. Wnddl. ex. Link) B. Hyland, Syzygium luehmannii (F. Muell.) L.A.S. Johnson, Syzygium jambos L. (Alston), Terminalia ferdinandiana Exell. and Tasmannia lanceolata (Poir.) A.C.Sm. are used in traditional Australian Aboriginal and Asian healing systems to treat a variety of pathogenic diseases including fungal skin infections, yet they are yet to be examined for the ability to inhibit the growth of human dermatophytes.Materials and methodsThe fungal growth inhibitory activity of extracts produced from selected Australian and Asian plants was assessed against a panel of human dermatophytes by standard disc diffusion and liquid dilution MIC methods. The toxicity of the extracts was evaluated by Artemia lethality and MTS HDF cell viability assays. The phytochemistry of the most promising extracts were examined by GC-MS headspace analysis and some interesting compounds were highlighted.ResultsThe aqueous and methanolic extracts of all plant species were good antifungal agents, inhibiting the growth of all of the dematophytes tested. The methanolic S. australe (SA) and S. luehmannii (SL) extracts were particularly potent fungal growth inhibitors. MIC values of 39 and 53 μg/mL were recorded for the methanolic SL fruit extract against T. mentagrophytes and T. rubrum respectively. Similar MICs were also noted for the methanolic SL leaf extract (88 and 106 μg/mL respectively). The methanolic SL leaf extract was a particularly good fungal growth inhibitor, with MIC values ≤ 100 μg/mL against the reference C. albicans strain (96 μg/mL), E. floccosum (53 μg/mL), and T. mentagrophytes (88 μg/mL). This extract also produced MICs ≤ 200 μg/mL against all other fungal species/strains tested. Similarly good activity was seen for the methanolic S. australe leaf and fruit extracts, as well as the S. lehmannii fruit and S. jambos leaf extracts, with MIC values 100-500 μg/mL. Interestingly, these extracts had low toxicity and high therapeutic indices, indicating their suitability for clinical use. GC-MS headspace analysis highlighted several monoterpenoids and sesquiterpenoids in the methanolic SA and SL extracts. T. ferdinandiana and T. lanceolata extracts also had promising antifungal activity, albeit with substantially higher MICs.ConclusionWhilst multiple extracts inhibited fungal growth, the methanolic S. australe and S. luehmannii leaf extracts and the S. luehmannii fruit extracts showed particularly potent activity against each of these dermatophytes, indicating that they are promising leads for the development of anti-dermatophytic therapeutics.     

Chemical composition,antioxidant activity and antifungal effects of five Iranian essential oils against Candida strains isolated from urine samples

Systemic candidiasis has become an emerging fungal infection in recent years. Anti-Candida resistance to conventional antifungal agents has subsequently increased. This study reported the chemical composition, antioxidant and anti-Candida activity of Origanum majorana, Artemisia dracunculus, Cymbopogon citrate, Cinnamomum verum and Caryophyllus aromaticus essential oils. Different Candida species, from urine tracts of hospitalized patients, were included to be challenged with understudied essential oils. Chemical compositions were determined using gas chromatography/mass spectroscopy (GC/MS) analysis and antioxidant activity was measured using DDPH assay. MIC of these essential oils was evaluated using broth micro-dilution test. Caryophyllus aromaticus had the highest antioxidant activity while the lowest antioxidant activity was for Artemisia dracunculus. MICs of Cinnamomum verum, Caryophillium aromaticus, Artemisia dracunculus, Origanum vulgare and Cymbopogon citratus essential oils ranged from 125 to 175 μg/mL (mean value: 147.7 ± 25.5 μg/mL), 700 to 1000 μg/mL (mean value: 740.9 ± 105.4 μg/mL), 1000 to 2000 μg/mL (mean value: 1454.5 ± 509.6 μg/mL), 173 to 350 μg/mL (mean value: 208 ± 55.8 μg/mL) and 125 to 175 μg/mL (mean value: 156.8 ± 24.6 μg/mL) for different Candida species, respectively. In general, natural compounds are suitable to be used as anti-Candida and antioxidant agents. However in this stage, these compounds could be applied as supplementary agents along with conventional antifungal drugs.     

Cytomegalovirus reactivation enhances the virulence of Staphylococcus aureus pneumonia in a mouse model

Objectives

Cytomegalovirus (CMV) reactivation in intensive care unit patients may increase mortality and favour bacterial pneumonia. We developed a murine model to compare the severity of staphylococcal pneumonia after CMV reactivation and in CMV-negative mice.

Isavuconazole: A new broad-spectrum azole. Part 1: In vitro activity

Triazoles compounds are first-line agents for the treatment of invasive fungal diseases. Isavuconazole is the most recent triazole compound, approved in 2015 by the FDA and the EMA to treat invasive aspergillosis and mucormycosis. We reviewed here the in vitro activity of isavuconazole against a vast spectrum of species. Isavuconazole MICs were evaluated using CLSI, EUCAST or Etest methods, with no significant differences between the technics. Low MIC₅₀ and MIC₉₀ (< 1 μg/mL) were described for isavuconazole against the majority of Candida spp., except for C. glabrata and C. krusei. In vitro activity against Aspergillus spp. varied according to the species with an overall MIC₉₀ of 1 μg/mL ranging from 0.125 μg/mL (A. fumigatus) to 16 μg/mL (A. niger, A. tubingiensis). As for Aspergillus, the activity of isavuconazole against agents of mucormycosis varies upon genus and species, with an overall MIC₉₀ from 4 (Rhizopus spp.) to 16 μg/mL (Rhizomucor spp. and Mucor spp.). Recently, to help detecting non-wild-type isolates, EUCAST committee has proposed ECOFFs values for C. albicans, C. parapsilosis and C. tropicalis (0.03 μg/mL), for Aspergillus fumigatus (2 μg/mL), A. nidulans (0.25 μg/mL), A. terreus (1 μg/mL), A. flavus (2 μg/mL) and A. niger (4 μg/mL). Moreover, clinical breakpoints (susceptible/resistant) were defined for Aspergillus fumigatus (1 μg/mL), A. nidulans (0.25 μg/mL) and A. terreus (1 μg/mL). Using these breakpoints, isavuconazole showed activity against the vast majority of fungi.     

Endurance training reduces exercise-induced acidosis and improves muscle function in a mouse model of sickle cell disease

Sickle cell disease (SCD) mice (Townes model of SCD) presented exacerbated exercise-induced acidosis and fatigability as compared to control animals. We hypothesize that endurance training could represent a valuable approach to reverse these muscle defects. Endurance-trained HbAA (HbAA-END, n = 10), HbAS (HbAS-END, n = 11) and HbSS (HbSS-END, n = 8) mice were compared to their sedentary counterparts (10 HbAA-SED, 10 HbAS-SED and 9 HbSS-SED mice) during two rest – exercise – recovery protocols during which muscle energetics and function were measured. In vitro analyses of some proteins involved in muscle energetics, pH regulation and oxidative stress were also performed. Exercise-induced acidosis was lower in HbSS-END mice as compared to their sedentary counterparts during both moderate (p < 0.001) and intense (p < 0.1) protocols. The total force production measured during both protocols was higher in trained mice compared to sedentary animals. In vitro analyses revealed that enolase/citrate synthase ratio was reduced in HbSS-END (p < 0.001) and HbAS-END (p < 0.01) mice compared to their sedentary counterparts. In addition, malondialdehyde concentration was reduced in trained mice (p < 0.05). In conclusion, endurance training would reverse the more pronounced exercise-induced acidosis, reduce oxidative stress and ameliorate some of the muscle function parameters in SCD mice.     

Oral acute toxicity study as well as tissues oxidative stress and histopathological disorders in edible camphor administered rats

In the South-western part of Nigeria, edible camphor (EC) infusions are used to treat pile, back pain, and erectile dysfunction, especially in preparation for sexual intercourse. We therefore carried out oral acute toxicity study, and then investigated the effects of various doses of EC on the activities of lactate dehydrogenase (LDH), catalase (CAT), and superoxide dismutase (SOD), as well as reduced glutathione (GSH) and malondialdehyde (MDA) levels in wistar rats. Oral LD₅₀ of EC was estimated to be 9487 mg/kg body weight. Based on this, thirty animals were divided into six groups of five rats each, and were orally administered various doses of EC (1, 2, 4, and 6 g/kg body weight) for seven days. Comparing all results with control, EC significantly increased serum LDH activity (4 and 6 g/kg), liver (6 g/kg) and kidney (4 and 6 g/kg) MDA levels, as well testis GSH levels (1 g/kg). CAT activities were significantly decreased in liver, kidney, and testis, and also lung GSH level by all the tested doses. For SOD, activities were significantly increased in liver and lung, but significantly decreased in kidney (2, 4, and 6 g/kg). Various pathological disorders were also seen following the various doses of EC administered, especially in liver, kidney and lung. Therefore, from our findings, it is evident that incessant, misuse or overconsumption of EC could lead to oxidative tissue damage in rats.     

Cytogenotoxicological defense of retinyl palmitate in the front damage of antineoplastics

Cancer, the multifactorial pathology and to date is the most lethal causes of death in the world. Cyclophosphamide (CPA) and doxorubicin (DOX) are the individually or combindly used two anticancer drugs. The antineoplastic drugs-mediated genetic instability can be overcome by using antioxidants. The study evaluated the cytogenotoxic modulatory potentials of retinyl palmitate (RP) caused by CPA and DOX in Swiss mice. For this, adult Mus musculus of either sex were divided equally regarding to the gender. Toxicogenetic effects were induced by the intraperitoneal (i.p.) administration of the CPA (20 mg/kg) and/or DOX (2 mg/kg), following to test for comet assay and micronucleus test in bone marrow cells after 48 h (DOX) and 7 h (CPA) of the administration of RP (100 IU/kg). Both CPA and DOX significantly (p < 0.05) increased with the index and frequency of damages, clastogenic and/or aneugenic effects with the augmenting of micronuclei, demonstrating the cytotoxicity interference on the ratio of normochromatic to polychromatic erythrocytes and bone marrow cells of mice, that were found to reduce in RP treatment groups. In conclusion, RP has a modulatory effect on CPA and DOX-mediated cytogenotoxic events. The findings may be a good indication to manage the antioneoplastic drug-induced stress mediated detrimental effects by using RP, especially as a side effect minimizer.     

Antioxidant,cytotoxic and antineoplastic effects of Carissa carandas Linn. leaves

For scientific clarification of some traditional uses, this study was designed to explore the antioxidant, cytotoxic and antineoplastic properties of leaf extract of Carissa carandas Linn., a traditional medicinal plant of Bangladesh. The methanol extract of Carissa carandas leaves (MELC) was applied on DPPH and ABTS experiments to determine its antioxidant activity. In vitro the cytotoxic effect of MELC was evaluated against colonic adenocarcinoma cell lines (SW-480 and SW-48) whereas in vivo its antineoplastic property was tested against Ehrlich ascites carcinoma (EAC). The DPPH and ABTS assays revealed the antioxidant activity of MELC with IC₅₀ 10.5 ± 1.2 and 1.75 ± 0.3 μg/ml that was comparable to L-ascorbic acid. In vitro cytotoxic study, MELC reduced the viability of adenocarcinoma cells in dose dependent manner and in vivo, administration of MELC (25 mg/kg) resulted in a significant (p < 0.05) decrease in viable EAC cell count thereby increasing the life span of the EAC cell bearing mice. Restoration of hematological parameters such as red blood cells (RBC), hemoglobin and white blood cells (WBC) to normal levels in MELC-treated mice was also observed. Moreover, treatment with MELC induced apoptosis of EAC cells as observed in fluorescence microscopic view of DAPI (4,6-diamidino-2-phenylindole) stained cells and also increased p53 gene expression MELC-treated cells in respect to untreated EAC control. In addition, the MELC was rich in polyphenol content and its GC–MS chromatogram confirmed the presence of some compounds all of which showed anticancer and cytotoxic activities in previous studies. In a word, this study supports the use of Carissa carandas in traditional medicine as well as highlights the need to further explore the potentials of MELC as an antineoplastic agent.     

In vitro antidermatophytic activity and cytotoxicity of extracts derived from medicinal plants and marine algae

Objectives

This study was conducted to evaluate the antidermatophytic activity of 48 extracts obtained from medicinal plants (Cibotium barometz, Melastoma malabathricum, Meuhlenbeckia platyclada, Rhapis excelsa, Syzygium myrtifolium, Vernonia amygdalina) and marine algae (Caulerpa sertularioides, Kappaphycus alvarezii) against Trichophyton rubrum and Trichophyton interdigitale (ATCC reference strains), and the cytotoxicity using African monkey kidney epithelial (Vero) cells. Active plant extracts were screened for the presence of phytochemicals and tested against clinical isolates of Trichophyton tonsurans.

Synthesis,characterization and antifungal activity of a novel formulated nanocomposite containing Indolicidin and Graphene oxide against disseminated candidiasis

Objective

Candidiasis is one of the most opportunistic fungal infections in immunocompromised patients. The emergence of multidrug-resistant Candida species necessitates the development of novel antifungal agents. Seeking to the discovery of natural antifungal agents, this study aimed to synthesize a novel formulated nanocomposite containing Indolicidin (IN), antimicrobial peptide, and Graphene oxide (GO), kind of nanomaterial, against Candida growth using in vitro and in vivo experiments for the first time.

Antidepressant-like activity of methyl jasmonate involves modulation of monoaminergic pathways in mice

Purpose

The efficacy of current antidepressant drugs has been compromised by adverse effects, low remission and delay onset of action necessitating the search for alternative agents. Methyl jasmonate (MJ), a bioactive compound isolated from Jasminum grandiflorum has been shown to demonstrate antidepressant activity but its mechanism of action remains unknown. Thus, the role of monoaminergic systems in the antidepression-like activity of MJ was investigated in this study.

Plateau–patella angle: An option for the evaluation of patellar height in patients with patellar instability

Background

Patellar instability is a debilitating disease. An important factor related to recurrent dislocation is patellar height. A new method of patellar height measurement, the plateau–patella angle (PPA), was proposed in 2011. However, to date, there is no study evaluating the use of this method in patients with patellar instability. The aim of this study was to evaluate the PPA in patients with recurrent patellar dislocation.

Extract of bulbus Fritillaria cirrhosa perturbs spindle assembly checkpoint,induces mitotic aberrations and genomic instability in human colon epithelial cell line

Background

Bulbus Fritillaria cirrhosa D. Don (BFC) has been used in China as a folk medicine for the treatment of cough and asthma for more than 2000 years. The antitussive and antiasthmatic effects of BFC have been reported before, nevertheless its toxicity and safety have not been documented. This study investigated the possible effects of BFC on spindle assembly checkpoint (SAC), mitotic fidelity and genomic stability in human NCM460 colon epithelial cells.

Statistical versus artificial intelligence -based modeling for the optimization of antifungal activity against Fusarium oxysporum using Streptomyces sp. strain TN71

A Streptomyces sp. strain TN71 was isolated from Tunisian Saharan soil and selected for its antimicrobial activity against phytopathogenic fungi. In an attempt to increase its anti–Fusarium oxysporum activity, GYM + S (glucose, yeast extract, malt extract and starch) culture medium was selected out of five different production media. Plackett–Burman design (PBD) was used to select yeast extract, malt extract and calcium carbonate (CaCO₃) as parameters having significant effects on antifungal activity, and a Box–Behnken design was applied for further optimization. The analysis revealed that the optimum concentrations for the anti–F. oxysporum activity of the tested variables were yeast extract 5.03 g/L, malt extract 8.05 g/L and CaCO₃ 4.51 g/L. Artificial Neural Networks (ANNs): the Multilayer perceptron (MLP) and the Radial basis function (RBF) were created to predict the anti–F. oxysporum activity. The comparison between experimental and predicted outputs from ANN and Response Surface Methodology (RSM) were studied. The ANN model presents an improvement of 14.73%. To our knowledge, this is the first work reporting the statistical versus artificial intelligence -based modeling for the optimization of bioactive molecules against mycotoxigenic and phytopathogenic fungi.     

Anatomical and molecular studies of cytochrome P450 family CYP7A1 gene polymorphism and its association with gallstone in north Indian population

Introduction

In this study, we have mainly focused on the molecular and biochemical aspects to know the cause of gall stone diseases in human. To know about these problems, there may be necessitating initiating interest in researchers of this field and to set up easily available tools and techniques. The screening of polymorphism with molecular approaches of P450 super family CYP7A1 gene was performed to explore its relation with gallstone diseases.

Protective effect of Tritone (Livosone) on oxidative DNA damage and its hepatoprotective potential against various hepatotoxic agent in wistar rats

Aim

To evaluate antioxidant activity, DNA damage inhibition and hepatoprotecitve potential of polyherbal formulation Tritone (Livosone).

Combined effects of deoxynivalenol and zearalenone on oxidative injury and apoptosis in porcine splenic lymphocytes in vitro

Deoxynivalenol (DON) and zearalenone (ZEA) are the two most common mycotoxins in animal feed. In this study, we examined oxidative injury and apoptosis of porcine splenic lymphocytes induced by DON or ZEA and their combination in vitro. Based on IC₅₀ values, porcine splenic lymphocytes were treated with 0.06, 0.3, 1.5, and 7.5 μg/mL DON, 0.08, 0.4, 2, and 10 μg/mL ZEA, or both DON and ZEA at 0.06 and 0.08 μg/mL, 0.3 and 0.4 μg/mL, and 1.5 and 2 μg/mL, respectively. After 48 h of DON and/or ZEA exposure, the cells were analyzed for antioxidant functions, apoptosis, and mRNA and protein expression of apoptosis-related genes p53, Bcl-2, Bax, caspase-3, and caspase-8 to determine their apoptosis and oxidative damage effects and mechanisms. The results showed that, compared with the control group, SOD, CAT, GPx, GSH, and Bcl-2 mRNA and protein expression levels were significantly reduced in exposed groups (P < 0.05 or P < 0.01). Furthermore, MDA contents, apoptosis rates, and p53, Bax, caspase-3 and caspase-8 protein and mRNA expression levels were increased significantly (P < 0.01). The effects of DON and ZEA were dose dependent and synergistic in combination. These data suggest that DON and ZEA induce oxidative damage and apoptosis of porcine splenic lymphocytes.     

Clinical predictors of the leading pathogens in human immunodeficiency virus-infected adults with community-onset bacteremia in the emergency department: The importance of transmission routes

Background/Purpose

To investigate the clinical characteristics and pathogens of community-onset bacteremia among human immunodeficiency virus (HIV)-infected adults as well as to establish the clinical predictors of the major microorganisms.