Toxicology Commons^™

Advanced Molecular Biologic Techniques In Toxicologic Disease, Jeanine Ward, Gyongyi Szabo, David Mcmanus, Edward Boyer

Gyongyi Szabo

The advancement of molecular biologic techniques and their capabilities to answer questions pertaining to mechanisms of pathophysiologic events have greatly expanded over the past few years. In particular, these opportunities have provided researchers and clinicians alike the framework from with which to answer clinical questions not amenable for elucidation using previous, more antiquated methods. Utilizing extremely small molecules, namely microRNA, DNA, protein, and nanoparticles, we discuss the background and utility of these approaches to the progressive, practicing physician. Finally, we consider the application of these tools employed as future bedside point of care tests, aiding in the ultimate goal of …

Interaction Of Fish Aryl Hydrocarbon Receptor Paralogs (Ahr1 And Ahr2) With The Retinoblastoma Protein, Rebeka Merson, Sibel Karchner, Mark Hahn

Rebeka Rand Merson

The aryl hydrocarbon receptor (AHR) mediates the toxic effects of 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) and related compounds. In some mammalian cell lines, TCDD induces G1 cell cycle arrest, which depends on an interaction between the AHR and the retinoblastoma tumor suppressor (RB). Mammals possess one AHR, whereas fishes possess two or more AHR paralogs that differ in the domains important for AHR-RB interactions in mammals. To test the hypothesis that fish AHR paralogs differ in their ability to interact with RB, we cloned RB cDNA from Atlantic killifish, Fundulus heteroclitus, and studied the interactions of killifish RB protein with killifish AHR1 and …

Occurrence And Biological Effect Of Exogenous Steroids In The Elkhorn River, Nebraska, Usa, Alan Kolok, Daniel Snow, Satomi Kohno, Marlo Sellin, Louis Guillette

Daniel D Snow

Recent studies of surface waters in North America, Japan, and Europe have reported the presence of steroidogenic agents as contaminants. The current study has three objectives: 1) to determine if steroidogenic compounds are present in the Elkhorn River, 2) to determine if sediments collected from the Elkhorn River can act as a source of steroidogenic compounds to aquatic organisms, and 3) to determine if site-specific biological effects are apparent in the hepatic gene expression of fathead minnows. Evidence was obtained using three approaches: 1) deployment of polar organic chemical integrative samplers (POCIS), 2) deployment of caged fathead minnows, and 3) …

Erectogenic Effects Of Clerodendron Capitatum: Involvement Of Phosphodiesterase Type-5 Inhibition, Dr Syam Mohan

Syam Mohan

No abstract provided.

Clausena Excavata Burm. F. (Rutaceae): A Review Of Its Traditional Uses, Pharmacological And Phytochemical Properties., Dr Syam Mohan

Syam Mohan

The present review describes the morphological, traditional, phytochemical and pharmacological aspects of Clausena excavata (Burm. f., Rutaceae). The plant grows wild in the tropical and subtropical parts of Asia and represents one of the richest sources of medicinal natural products. It is intensively used currently in traditional medicine for treatment of different illnesses. One part or a mixture of two or more parts of the plant in the form of powder or liquid doze is usually given to the patient. Phytochemically, many pure compounds from several secondary metabolite groups of C. excavata have been isolated from different parts of the …

Chloroform Fraction Of Centratherum Anthelminticum (L.) Seed Inhibits Tumor Necrosis Factor Alpha And Exhibits Pleotropic Bioactivities: Inhibitory Role In Human Tumor Cells, Dr Syam Mohan

Syam Mohan

We investigated the antioxidant potential, cytotoxic effect, and TNF-α inhibition activity with NF-κB activation response in a chloroformfraction of Centratherum anthelminticum seeds (CACF). The antioxidant property of CACF was evaluated with DPPH, ORAC, and FRAP assays, which demonstrated significant antioxidant activity. The cytotoxicity of CACF was tested using theMTT assay; CACF effective inhibitory concentrations (IC50) for A549, PC-3, MCF-7, and WRL-68 cells were 31.42 ± 5.4, 22.61 ± 1.7, 8.1±0.9, and 54.93±8.3 μg/mL, respectively. CACF effectively and dose-dependently inhibited TNF-α release, in vitro and in vivo. CACF inhibited TNF-α secretion in stimulated RAW264.7macrophage supernatants with an IC50 of 0.012 μg/mL, …

In Vitro Anti-Inflammatory, Cytotoxic And Antioxidant Activities Of Boesenbergin A, A Chalcone Isolated From Boesenbergia Rotunda (L.) (Fingerroot), Dr Syam Mohan

Syam Mohan

The current in vitro study was designed to investigate the anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A (BA), a chalcone derivative of known structure isolated from Boesenbergia rotunda. Human hepatocellular carcinoma (HepG2), colon adenocarcinoma (HT-29), non-small cell lung cancer (A549), prostate adenocarcinoma (PC3), and normal hepatic cells (WRL-68) were used to evaluate the cytotoxicity of BA using the MTT assay. The antioxidant activity of BA was assessed by the ORAC assay and compared to quercetin as a standard reference antioxidant. ORAC results are reported as the equivalent concentration of Trolox that produces the same level of antioxidant activity as …

Synthesis Of Chalcones With Anticancer Activities., Dr Syam Mohan

Syam Mohan

Several chalcones were synthesized and their in vitro cytotoxicity against various human cell lines, including human breast adenocarcinoma cell line MCF-7, human lung adenocarcinoma cell line A549, human prostate cancer cell line PC3, human adenocarcinoma cell line HT-29 (colorectal cancer) and human normal liver cell line WRL-68 was evaluated. Most of the compounds being active cytotoxic agents, four of them with minimal IC50 values were chosen and studied in detail with MCF-7 cells. The compounds 1, 5, 23, and 25 were capable in eliciting apoptosis in MCF-7 cells as shown by multiparameter cytotoxicity assay and caspase-3/7, -8, and -9 activities …

Cucurbitacin L 2-O- Glucoside Demonstrates Apoptogenesis In Colon Adenocarcinoma Cells (Ht-29): Involvement Of Reactive Oxygen And Nitrogen Species Regulation, Dr Syam Mohan

Syam Mohan

Emerging evidence suggests that reactive oxygen (ROS) and nitrogen (RNS) species can contribute to diverse signalling pathways of inflammatory and tumour cells. Cucurbitacins are a group of highly oxygenated triterpenes. Many plants used in folk medicine to treat cancer have been found to contain cucurbitacins displaying potentially important anti-inflammatory actions. The current study was designed to investigate the anti-ROS and -RNS effects of cucurbitacin L 2-O-β-glucoside (CLG) and the role of these signaling factors in the apoptogenic effects of CLG on human colon cancer cells (HT-29). This natural cucurbitacin was isolated purely from Citrullus lanatus var. citroides (Cucurbitaceae). The results …

Dentatin Induces Apoptosis In Prostate Cancer Cells Via Bcl-2, Bcl-Xl, Survivin Downregulation, Caspase-9, -3/7 Activation And Nf-Kb Inhibition., Dr Syam Mohan

Syam Mohan

This study was set to investigate antiproliferative potential of dentatin (a natural coumarin isolated from Clausena excavata Burm. F) against prostate cancer and to delineate the underlying mechanism of action. Treatment with dentatin dose-dependently inhibited cell growth of PC-3 and LNCaP prostate cancer cell lines, whereas it showed less cytotoxic effects on normal prostate epithelial cell line (RWPE-1). The inhibitory effect of dentatin on prostate cancer cell growth was due to induction of apoptosis as evidenced by Annexin V staining and cell shrinkage. We found that dentatin-mediated accumulation of reactive oxygen species (ROS) and downregulated expression levels of antiapoptotic molecules …

Excessive Dietary Calcium In The Disruption Of Structural And Functional Status Of Adult Male Reproductive System In Rat With Possible Mechanism, A K. Chandra, Pallav Sengupta, Haimanti Goswami, Mahitosh Sarkar

Pallav Sengupta, PhD