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.

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.

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.