Effective treatment of resistant opportunistic fungi associated with immuno-compromised individuals using silver biosynthesized nanoparticles.

Drug resistance in filamentous fungus to antifungal medicines is a huge problem in biomedical applications; so, an effective strategy for treating opportunistic fungal infections is needed. Mentha piperita is a very fascinating plant to treat a variety of ailments as home remedies. Eighteen strains of Aspergillus species were used for this study which are having a unique antifungal resistance profile in presence of silver nanoparticles (AgNPs). AgNPs were prepared, using an aqueous extract of M. Piperita and characterized it by various techniques. Structural properties of AgNPs were systematically studied using X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), Fourier-transform infrared spectroscopy (FT-IR), and Raman measurement, which emanate the single-phase fcc structure of silver nanoparticles. The spherical nature and elemental analysis of as-synthesized AgNPs were confirmed using scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) spectroscopy, respectively. The optical study has been analyzed using UV-Vis spectroscopy and band gap was calculated as 2.51 eV, using Tauc plot. To analyze and validate the good efficacy of the disc approach, antifungal activity of AgNPs nanoparticles in different concentrations against isolates was achieved in both disc and broth microdilution. The extracellular enzymatic activity of A. fumigatus was found to explore the precise impact of nanoparticles on fungal metabolism. The antifungal efficacy of AgNPs against all fungi was highly successful in disc method. The broth approach underlined the favorable results of the disc method. It provided more precise results in determining the minimum inhibition concentration (MIC), as well as the minimum effective concentration (MEC). A. fumigatus (AM6) enzymatic activity was boosted by AgNPs. Also, ß-galactosidase, ß-glucuronidase, and ß-glucosidase are necessary enzymes whose activity has been boosted. Consequently, M. piperita AgNPs can play a major and intriguing function against resistant Aspergillus species with a significant shift in the enzymatic activity profile of fungi due to this action.

Potassium bromate-induced oxidative stress, genotoxicity and cytotoxicity in the blood and liver cells of mice.

Potassium bromate (KBrO3) is an oxidising agent that is extensively used as a food additive, it is also a product of cosmetic and pharmaceutical relevance. The objective of this study was to evaluate the oxidative stress, genotoxicity, and apoptosis induced by KBrO3 in an experimental animal model. To study the toxic effects and oxidative stress, different doses of KBrO3 below LD50 (The half maximal lethal dose, 50, 100 and 150 mg/kg body weight) were given intraperitoneally to the mice for multiple time periods (24, 48, and 72 h). The results showed that KBrO3 significantly induces oxidative damage by increasing the levels of reactive oxygen species (ROS) and lipid peroxidase and depleted the levels of catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) enzymes in the serum and liver. Moreover, a significant increase of chromosomal aberrations in bone marrow cells and an elevated incidence of micronuclei in the peripheral blood of mice were observed. KBrO3 induces 3 ´ -OH end double-strand DNA breaks, which was evident in liver sections of the treated mice, and increases the percentage of apoptotic cells, as observed in TUNEL assays and flow cytometry analysis. The present findings indicate that KBrO3 induces oxidative stress, genotoxicity, and cytotoxicity in a dose- and time-dependent manner in mice.

Reactive Oxygen Species-Mediated Cytotoxicity in Liver Carcinoma Cells Induced by Silver Nanoparticles Biosynthesized Using Schinus molle Extract.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is ranked as the third most common cause of cancer-related mortality worldwide. Schinus molle (S. mole) L. is an important medicinal plant that contains many bioactive compounds with pharmacological properties. The role of S. molle leaf extract in the biosynthesis of silver nanoparticles (AgNPs) was determined. The biosynthesized AgNPs were thoroughly characterized by UV-vis spectrophotometry, transmission electron microscopy (TEM), X-ray diffraction (XRD), and dynamic light scattering (DLS) techniques. Furthermore, the cytotoxic effect of the biosynthesized AgNPs using S. molle (SMAgNPs) against HepG2 liver cancer cells was investigated. Reactive oxygen species generation, apoptosis induction, DNA damage, and autophagy activity were analyzed. The results clearly showed that the biosynthesized silver nanoparticles inhibited the proliferation of HepG2 by significantly (p < 0.05) inducing oxidative stress, cytotoxicity, DNA damage, apoptosis, and autophagy in a dose- and time-dependent manner. These findings may encourage integrating the potential of natural products and the efficiency of silver nanoparticles for the fabrication of safe, environmentally friendly, and effective anticancer agents.

Amelioration of indole acetic acid-induced cytotoxicity in mice using zinc nanoparticles biosynthesized with Ochradenus arabicus leaf extract.

The diversity of natural phytochemicals represents an unlimited source for discovery and development of new drugs. Ochradenus arabicus, (family: Resedaceae) a notable medicinal plant displays a high content of flavonoid glycosides. This study investigates a possible preventative role of zinc nanoparticles biosynthesized by O. arabicus leaf extracts (OAZnO NPs) in limiting genotoxicity and cytotoxicity caused by indole acetic acid (IAA) in laboratory mice. ZnO NPs were synthesized using O. arabicus leaf extracts and characterized with UV-visible spectroscopy, scanning electron microscopy (SEM) and X-Ray diffraction (XRD). The mice were randomly distributed into the following six groups: control, OAZnO NPs treated (10 mg/kg BW), IAA treated (50 mg/kg BW); simultaneous treatment, pre-treatment, and post-treatment. Reactive oxygen species (ROS), DNA damage, chromosome aberration, and apoptosis were analyzed as toxicity endpoints. IAA exposure significantly induced production of ROS, DNA damage, apoptosis, chromosome aberrations, and micronuclei. Pre-, post-, and simultaneous treatment with OAZnO NPs ameliorated the damage caused by IAA exposure. Exposure to OAZnO NPs alone caused no toxicity for any endpoint based on comparison to controls. This study demonstrated that IAA-induced cytotoxic damage in mice could be ameliorated by treatment with OAZnO NPs. These findings require additional verification in mechanistic and in vitro studies.

Protective Effect of Capparis spinosa Extract against Potassium Bromate Induced Oxidative Stress and Genotoxicity in Mice.

Despite the commercial value of potassium bromate (KBrO3), it has been linked to many diseases including cancer. Capparis spinosa possesses exceptional ethnobotanical, pharmaceutical, and economic prominence by virtue of its bioactive components. The present study was designed to explore the protective role and antioxidant potential of ethanolic leaves extract of C. spinosa against the oxidative stress, genotoxicity, and apoptosis induced by KBrO3 in an experimental animal model. The results of the study revealed remarkable diminution in the levels of oxidative stress in all the treatment groups. C. spinosa extract attenuated the toxic effects of KBrO3 significantly (p < 0.05) in a time- and dose-dependent manner by restoring the normal levels of ROS and antioxidative enzymes in serum and liver tissues. The extract also abolished the oxidative DNA damage as it was evident in decreased frequency of micronuclei. A marked increase in viable cells was observed in annexin-V apoptosis assay. In conclusion, the findings of the present study demonstrate that ethanolic leaves extract of C. spinosa has considerable protective effects against KBrO3-induced toxicity in experimental mice which is attributed to its antioxidant activity. Therefore, leaves of C. spinosa could be used as a potential source of natural antioxidant and bioactive compounds.

Samsum ant venom protects against carbon tetrachloride-induced acute spleen toxicity in vivo.

Many active molecules used in the development of new drugs are produced by ants. Present study assessed antioxidant and anti-inflammatory properties of Samsum ant venom (SAV) extract in carbon tetrachloride (CCL4)-induced spleen toxicity. Toxicity and oxidative stress were measured in four experimental groups: a negative control group without any treatment, a positive control group (CCl4-treated rats; a single dose of 1 ml/kg CCL4), an experimental group of CCl4-treated rats co-treated daily with SAV (100 µl), and a group to determine safe use with rats treated only with SAV (100 µl) daily for 3 weeks. CCl4-treatment led to an elevation in toxicity and oxidative stress. CCl4 significantly elevated malondialdehyde (MDA) levels, as well as expression of inhibitor of κB (IκB) and tumor necrosis factor-α (TNF-α) proteins. On the other hand, a decrease in glutathione (GSH) and catalase (CAT) levels were detected in CCl4-treated rats. Co-treatment with SAV was found to reduce these inflammatory and oxidative parameters. SAV elucidated a significant recovery of MDA concentration as well as a significant restoration in GSH levels compared to CCl4-treated rats; however, SAV increased CAT levels compared to normal rats. Hence, SAV was found to restore splenomegaly induced in CCl4-treated rats. Histopathological analysis also favored the biochemical analysis showing improvement in splenic architecture in CCl4 and SAV co-treated rats. The antioxidant properties of SAV may potentially enhance anti-inflammatory actions and improve spleen structure and function in CCl4-challenged rats.

In Silico Elucidation of the Plausible Inhibitory Potential of Withaferin A of Withania Somnifera Medicinal Herb Against Breast Cancer Targeting Estrogen Receptor.

BACKGROUND: Estrogen Receptors (ER) are members of the nuclear intracellular receptors family. ER once activated by estrogen, it binds to DNA via translocating into the nucleus and regulates the activity of various genes. Withaferin A (WA) - an active compound of a medicinal plant Withania somnifera was reported to be a very effective anti-cancer agent and some of the recent studies has demonstrated that WA is capable of arresting the development of breast cancer via targeting estrogen receptor. OBJECTIVE: The present study is aimed at understanding the molecular level interactions of ER and Tamoxifen in comparison to Withaferin A using In-silico approaches with emphasis on Withaferin A binding capability with ER in presence of point mutations which are causing de novo drug resistance to existing drugs like Tamoxifen. METHODS: Molecular modeling and docking studies were performed for the Tamoxifen and Withaferin A with the Estrogen receptor. Molecular docking simulations of estrogen receptor in complex with Tamoxifen and Withaferin A were also performed. RESULTS: Amino acid residues, Glu353, Arg394 and Leu387 was observed as crucial for binding and stabilizing the protein-ligand complex in case of Tamoxifen and Withaferin-A. The potential of Withaferin A to overcome the drug resistance caused by the mutations in estrogen receptor to the existing drugs such as Tamoxifen was demonstrated. CONCLUSION: In-silico analysis has elucidated the binding mode and molecular level interactions which are expected to be of great help in further optimizing Withaferin A or design / discovery of future breast cancer inhibitors targeting estrogen receptor.

Gemcitabine induced cytotoxicity, DNA damage and hepatic injury in laboratory mice.

The present study was conducted to demonstrate cytotoxicity, apoptosis and hepatic damage induced by gemcitabine in laboratory mice. Animals were treated with a single dose of gemcitabine (415 mg/kg body wt), equivalent to a human therapeutic dose, and sacrificed after 1, 2 and 3 weeks. A significant decrease in mean body weight and absolute liver weight was registered. The levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were increased as a result of this induced stress. Various structural changes were observed in the liver tissue of treated mice, as evident in the histological sections. Specifically, gemcitabine exposure was able to induce apoptosis in liver cells, and the incidence of TUNEL positive liver cells was increased compared to the control group. DNA fragmentation appeared on agarose gel and flow cytometry analysis confirmed the induction of apoptosis. These findings in gemcitabine-treated animal tissues suggest that inhibition or disruption of cells' DNA synthesis may be the mechanism by which this drug induces toxicity in the animal body.

Cytogenotoxic effects of Adenium obesum seeds extracts on breast cancer cells.

The extracts prepared from various areal parts of the Adenium obesum (Forssk.) Roem. & Schult. (Family: Apocynaceae) including leaves, fruit and seeds ethanolic extracts and seed aqueous extract were evaluated against MCF-7 cells in order to investigate its potential of cytogenotoxicity and induction of apoptosis. The ethanolic seeds extract had comparatively higher cytotoxicity (IC50 ∼ 337 µg/ml). Further, apoptosis and DNA damaging potential of seeds ethanolic extract was analyzed by applying multiple sub-lethal concentrations and durations. Flow cytometry results revealed that maximum percentage of early apoptosis (37%) and late apoptosis (35%) were observed after 12 h exposure in concentrations 200 µg/ml and 300 µg/ml, respectively. Similarly, the higher effect of extract in terms of DNA damage by alkaline comet assay was registered after 12 h treatment at concentrations 200 and 300 µg/mL. The calculated total damage score (TDS) for these concentrations were 614 and 617, respectively. The above findings indicate that A. obesum ethanolic seeds extracts has cytogenotoxic properties that could be further explored for the potential source of chemotherapeutic lead against cancer.

Ovarian development and histological observations of threatened dwarf snakehead fish, Channa gachua (Hamilton, 1822).

Channa gachua were monthly sampled throughout a year and the histological analysis of their ovaries was done to determine the changes occurring in ovarian development. Based on histological examination of the ovaries, the oogenic process of C. gachua undergoes distinct cyclic and seasonal morphological changes. Five different developmental stages were identified under three major categories: pre-spawning (immature, maturing, mature), spawning (ripe-running) and post-spawning (spent). The peak spawning period of C. gachua was noticed during December - February. The gonadosomatic index (GSI) and ova diameter ranged from 0.79 to 3.61% and 543-1123 µm respectively. The highest mean GSI (3.61 ± 0.16) and oocyte diameter (1123 ± 55 µm) were observed in December indicating that during this month the gonadal development reached maturity.