Narrow Results

The toxic effects of oral administration of 0.25 g/kg Nerium oleander leaves, 0.25 g/kg Rhazya stricta leaves or their mixture at 0.25 g/kg N. oleander leaves plus 0.25 g/kg R. stricta leaves on Najdi sheep were investigated. Daily oral dosing of R. stricta leaves for 42 days was not fatal to sheep while single oral doses of either N. oleander leaves or the mixture with R. stricta leaves proved fatal to animals within 24 hours with dyspnea, grunting, salivation, grinding of the teeth, ruminal bloat, frequent urination, ataxia and recumbency prior to death. The main lesions were widespread congestion or hemorrhage, pulmonary cyanosis, emphysema, bronchotracheal froths, and hepatonephropathy. The clinical and pathological changes were correlated with alterations in serum LDH and AST activities and concentrations of cholesterol, bilirubin, urea, total protein, albumin, and globulin and hematological values.

The toxic effects of diet containing 10% of C. senna L. fruits or 10% of N. oleander L. leaves or their 1 : 1 mixture (5%+5%) on male Wistar rats treated for 6 weeks were investigated. Diarrhea was a prominent sign of C. senna L. toxicosis. In both phytotoxicities, there were decreases in body weight gains, inefficiency of feed utilization, dullness and enterohepatonephropathy. These findings accompanied by leukopenia and anemia were correlated with alterations of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities and concentrations of total protein, albumin, urea and other serum constituents. In both phytotoxicities, the ability of the liver to excrete bilirubin remained unchanged. Feeding the mixture of C. senna L. fruits and N. oleander L. leaves caused more serious effects and death of rats. The implications of these findings are discussed.

The effect of 5, 10, 20, 40 and 80 mg/kg b. wt. of hydroalcoholic extract of geriforte (an Ayurvedic herbal medicine) administered intraperitoneally was studied on the radiation-induced mortality in mice exposed to 10 Gy of γ-radiation. Treatment of mice with different doses of geriforte consecutively for 5 days before irradiation delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug treated irradiated controls. A maximum protection was observed for 10 mg/kg geriforte, where a highest number of survivors were reported by 30 days post-irradiation and further experiments were carried out using this dose of geriforte. The mice were treated with 10 mg/kg b. wt. geriforte or double distilled water (DDW) and exposed to 7, 8, 9, 10 and 11 Gy of gamma radiation and observed for the induction of symptoms of radiation sickness and mortality up to 30 days post-irradiation. The geriforte treatment protected the mice against the GI death as well as bone marrow deaths and the dose reduction factor (DRF) was found to be 1.14. Toxicity study showed that geriforte was non-toxic up to a dose of 4250 mg/kg, where no drug-induced mortality was observed. The LD₅₀ dose of geriforte was found to be 4750 mg/kg b. wt. To understand the mechanism of action of geriforte, free radical scavenging activity of the drug was evaluated. Geriforte was found to scavenge ^•OH, O₂^•-ABTS^•+ and NO^• in a dose-dependent manner. Our study demonstrates that geriforte is a good radioprotective agent and the optimum protective dose of 10 mg/kg was 1/475th of the LD₅₀ dose.

Ginseng is one of the most popular herbal supplements on the US market. Numerous reports of adverse effects from products containing ginseng have been filed with the US Food and Drug Administration (FDA) and the literature documents a "ginseng abuse syndrome" among regular users. However, the chronic toxic effects of ginseng are not well characterized. Because of its significant human exposure and the fact that little information on its toxicity is available, Panax ginseng was nominated by the US National Institutes of Health (NIH) to the US National Toxicology Program (NTP) to assess its carcinogenic potential. In this paper, we reported the results of NTP chronic toxicity and tumorigenicity bioassay. It shows that, under these experimental conditions, Panax ginseng is not toxic or tumorigenic.

Aloe-emodin (AE), a bioactive anthraquinone derived from both Aloe vera and Rheum officinale, has recently been demonstrated to have various pharmacological activities. With the widespread popularity of natural products, such as antineoplastic drugs, AE has attracted much attention due to its remarkable antineoplastic activity on multiple tumor cells involving multi-channel mechanisms, including the disruption of cell cycle, induction of apoptosis, anti-metastasis, antiangiogenic, and strengthening of immune function. Experimental data have revealed AE as a potentially potent anti-cancer candidate. Despite this, the pharmaceutical application of AE is still in a fledging period as most research has concentrated on the elucidation of the molecular mechanism of action of existing treatments, rather than the development of novel formulations. Therefore, the present review summarizes the potential toxicity, molecular mechanism, pharmacokinetic characteristics, and pharmaceutical development of AE as an antineoplastic agent. This is based on its physicochemical properties, in an attempt to encourage further research on AE as a potential anti-cancer agent.

Kansui, the root of Euphorbia kansui T.N. Liou ex T.P. Wang, is a well-known traditional Chinese medicine. This paper reviews advances in investigations of the botany, the phytochemistry, the analytical method, the pharmacology and the toxicology of kansui. Nearly 100 compounds have been isolated from kansui and identified, and diterpenes and triterpenes are considered to be the characteristic and bio-active constituents of kansui. They possess multiple pharmacological activities, including diuretic, purgation, and antitumor effects. However, they also have a degree of toxicity, and can cause skin, oral, and gastrointestinal irritation. In this paper, the toxicity-efficacy relationship, attenuation and incompatibility of kansui are further discussed. Several future investigations of kansui are also proposed, all of which would improve the identification of kansui and other toxic herbs, as well as further their utilization.

Toxic Chinese materia medica (CMM) has both pharmacological activities and toxic effects. Based on thousands of years of experience in the application of CMMs, people have explored many practical processing methods of CMMs, also known as “Pao Zhi”, to reduce/control toxicity and preserve/enhance efficacy. Toxic CMMs have been used throughout China’s hospitals. Yet, the production and use of toxic CMM should be carried out in accordance with the Chinese pharmacopoeia (ChP) and the processing regulations formulated by the health administrative departments of provinces, autonomous regions, and municipalities directly under the Central Government. This paper summarizes the current understanding and awareness of toxicity and 45 toxic CMMs, the commonly used processing methods of toxic CMMs recorded in the 2020 edition of ChP, and the changes in the chemical component, toxicity, or efficacy profiles after processing. This review may provide useful information for the processing methods of toxic CMMs worldwide. We believe that with an in-depth study and understanding of toxic CMMs combined with a standardized application, the toxicity of CMMs will be predictable and controllable in the future.

$\beta$-Escin is an oleanane-type pentacyclic triterpenoid saponin extracted from the seeds of Aesculus hippocastanum (AH), which is more widely distributed. $\beta$-Escin sodium has been approved by the American FDA for clinical usage. This paper is intended to summarize an updated and comprehensive review of the pharmacological activities, pharmacokinetic properties, toxicity, and analytical methods of $\beta$-escin. Studies have shown that $\beta$-escin has significant antitumor, antiviral, anti-inflammatory, and other activities alongside less adverse effects and higher safety than other compounds. The review shows that the pharmacological effects of $\beta$-escin involve mechanisms such as ATM/$\gamma$H2AX, RhoA/Rock, GSK-3$\beta$/$\beta$-Catenin, HER2/HER3/Akt, and PI3K/Akt signaling pathways, and Cyclin A, p21${}^{WAF1∕CIP1}$, survivin, Bcl-2, Mcl-1, Caspases, TGF-$\beta$, MMPs, and TNF-$\alpha ,$ among other inflammatory factors. $\beta$-Escin has significant cytotoxicity; the use of the chitosan/xanthan gum-based polyelectrolyte complexes PA1 and PC-11 to modify it not only to reduces its toxicity, but also improves its drug efficacy. Because of this, these compounds may become a new research hotspot. $\beta$-Escin in vivo metabolism can be converted by the CYP1A2 enzyme in the intestinal flora to produce $\alpha$-escin, deacylated, deglycosylated, and 21$\beta$-$O$-crotonoyl-protoescin, and the binding rate of the plasma proteins is higher than 90%. These are mainly metabolized by the liver, kidneys, and other organs, and excreted in the form of urine and feces. The number of reports on the specific mediators of the metabolism of $\beta$-escin and their mechanisms and metabolites is relatively small; furthermore, the results are vague. Therefore, a complete and in-depth exploration of the pharmacokinetic characteristics of $\beta$-escin is needed to provide a more complete and effective theoretical reference for the study of its pharmacodynamic activity.

Analytical modeling and computer simulation may provide an assessment for the success of different cancer therapeutic strategies (both maximum tolerable dosing and metronomic dosing), particularly for the presence of microscopically dormant cells. Different authors substantially showed that metronomic strategy is better than maximum tolerable dosing. In the present work, the different physiological constraints have been considered. Accumulation of drug, dead tumor cells as well as metabolites produced by living tumor cells produce toxicity that affect the physiological system. This affects the subsequent drug application and thereby the therapeutic procedure and its outcome. Translating these into logistics and incorporating them into analytical state-space models, the transformation of the overall system has been examined through computer simulations. The observation is that situations of frequent drug stoppages may occur due to patho-physiological constraints, which may in turn inactivate the cell-mediated immune response. Simulation results suggest that even the combination of different strategies does not improve the situation. Other ways of boosting the immunity and tuning of biological constraints would be required to get positive outcome.

In the last century, mercury levels in the global environment have tripled as a result of increased pollution from industrial, occupational, medicinal and domestic uses.¹ Glutathione is known to be the main agent responsible for the excretion of mercury (Refs. 2 to 4). It has also been shown that mercury inhibits glutathione synthetase (an enzyme acting in the synthesization of glutathione), therefore leading to decreased glutathione levels (Refs. 5 to 7). Mercury also interferes with the production of heme in the porphyrin pathway.⁸ Heme is needed for biological energy production and ability to detox organic toxins via the P450 enzymes.⁹ The purpose of this paper is to show that the body's response to mercury exposure is hysteretic, i.e. when this feedback of mercury on its main detoxifying agents is strong enough, then mercury body burden has two points of equilibrium: one with normal abilities to detoxify and low levels of mercury and one with inhibited abilities to detoxify and high levels of mercury. Furthermore, a small increase of the body's mercury burden may not be sufficient to trigger observable neurotoxic effects but it may be sufficient to act as a switch leading to an accumulation of mercury in the body through environmental exposure until its toxicity is manifested.

The Concorde trial shows an increase in CD4⁺ lymphocytes, but not a higher survival, in AZT treated asymptomatic patients. Our murine bone-marrow experiments show that in chronic AZT treatments a large increase in the lymphoids/erythroids compartment is due to host cytotoxicity. We put forward a mathematical formula for predicting cytotoxicity of given drug protocols, which can be used for modulating the schedule so as to increase its efficacy while maintaining its toxicity low. Our study suggests that in chronic treatments a large, single, daily dose will be less toxic than the same dose divided into several daily dosings.

The use of NPs in the health care field is increasing. Before their biological application, investigating the toxicities of both n-type ZnO nanoparticles (NPs) and nitrogen-doped (“p-type”) NPs is important. Using L929 cells, the cell viability, oxidative stress, apoptosis induction, inflammatory responses, and cellular uptake were assayed 24h after the addition of n-type ZnO NPs and nitrogen-doped NPs (which act as p-type) (25$\mu$g/mL). The ZnO NPs were fabricated using a gas evaporation method. Increased H₂O₂ generation and decreased levels of glutathione were more evident in with n-type than in those treated with nitrogen-doped (“p-type”) ZnO NPs. Caspase-3/-7 activity was higher in cells treated with n-type ZnO NPs than in those treated with nitrogen-doped (“p-type”) NPs. Elevated levels of TNF-$\alpha$ and IL-1$\beta$ were observed in cell culture supernatants: IL-1$\beta$ levels were higher in n-type ZnO NPs than nitrogen-doped (“p-type”) NPs. The cellular Zn uptake of n-type ZnO NPs was higher than nitrogen-doped (“p-type”) NPs. These findings show that n-type ZnO NPs have higher cytotoxicity than nitrogen-doped (“p-type”) ZnO NPs. This may be due to a reductive effect of n-type ZnO NPs that induces higher free radical production, reactive oxygen species (ROS) generation, and cellular uptake of this type of ZnO NPs.

The article is discusses about the importance of Chinese herbal medicine in the millenium. It explains the toxicity of herbal ingredients, contamination and drug interactions.

Agilent collaborates with Gachon University to discover biomarkers for cancer and diabetes.

Population Genetics collaborates with Cambridge University to unravel the genetic causes of Asperger Syndrome.

Medicyte GmbH and Reinnervate Ltd to collaborate on development of next generation predictive 3D cell toxicity assays.

Agilent Technologies and Samsung Medical Center to collaborate on clinical research projects.

German Biotech innovator Altona DIAGNOSTICS launches BionexusNexus-Certified regional hub in Malaysia: ADT Biotech Sdn Bhd.

Bosch Packaging Technology has enhanced competences in process technology.

AstraZeneca completes sale of Aptium Oncology assets.

Avacta expands following Aptuscan acquisition.

Angiotech founder joins Union MedTech & Octa Phillip Bioscience Managers global team.

Greenphire appoints John Blakeley Chief Commercial Officer.

Applying Nano-Scale Technologies to Make Big Ideas Possible.

Toxicity of Engineered Nanomaterials.

Graphene for Smart Medical Devices.

Protein Nanocages: The Versatile Molecular Shell.

SINGAPORE – International Collaboration to Advance Research on Non-Animal Approaches to Chemical Safety Testing.

UNITED STATES – Coriell Institute Licenses PluriTest, a Novel Stem Cell Technology.

UNITED STATES – Tackling World's Problems with Human-Computer Intelligence.

UNITED STATES – Untapped Region in Brain Cell Offers Goldmine of Drug Targets for New Autism Treatments, UCLA Study Finds.

UNITED STATES – Activating Beige Fat in Humans Could Combat Obesity.

UNITED STATES – Cancer-Killing Proteins Destroy Tumor Cells in Bloodstream.

UNITED STATES – Measuring the Mechanical Forces of Disease.

UNITED STATES – Scientists Identify Molecule That Appears to Fuel Deadly Genetic Illness.

AUSTRALIA – Medlab Supports New Federal Legislation for Medical Cannabis.

UNITED KINGDOM – BioAscent Expands Compound Management Services Offering with Pierre Fabre Collaboration.

SWITZERLAND – Harmful Mutations Have Accumulated during Early Human Migrations Out of Africa.

JAPAN – BIOTRONIK's Itrevia 7 HF-T is First CRT-D Approved for Full-Body MRI Scanning in Japan.

SINGAPORE – VIVA Foundation and NUS Launches $10 Million Cancer Research Centre for Childhood Leukaemia.

SINGAPORE – Discovery Paves the Way for Potential Genetics-Guided Precision Medicine for Paediatric Leukaemia Patients.

SINGAPORE – Partnership between Sony and Alder Hey Children's Hospital Drives Innovation in Children's Healthcare.

UNITED STATES – UGA Researchers Make Link between Genetics and Aging.

UNITED STATES – Latin Dancing may Have Health Benefits for Older Adults.

UNITED STATES – Interferon Not Beneficial for Most Stage III Melanoma.

UNITED STATES – Dissecting the Animal Diet, Past and Present.

UNITED STATES – Water Conservation Important to Many; Only Some Take Action.

UNITED KINGDOM – Innova Biosciences Introduces New LATEX One-Step Conjugation Kits.

UNITED KINGDOM – New Understanding of the Mechanism of Neurodegeneration Leads to a Novel Approach to Treatment for Alzheimer's Disease.

TAIWAN – Breakthrough in Homogeneous Antibody Development and a New Generation of Glycoarray Technology.

TAIWAN – Increasing Protein Synthesis by Leucine Ameliorates Synaptopathy Caused by Dementia, ALS and Autism.

The following topics are under this section:

• Empowering the Consumer in Heart Health Management
• Game Changers – Triple-Threat Start-up Technology to shake up both Food and Biomedical industries
• The Lab report - Researchers from National University of Singapore looking to discover novel metal-based anticancer drugs with reduced toxicity.

Xenobiotics biotransformation in humans is a process of the chemical modifications, which may lead to the formation of toxic metabolites. The prediction of such metabolites is very important for drug development and ecotoxicology studies. We created the web-application MetaTox (http://way2drug.com/mg) for the generation of xenobiotics metabolic pathways in the human organism. For each generated metabolite, the estimations of the acute toxicity (based on GUSAR software prediction), organ-specific carcinogenicity and adverse effects (based on PASS software prediction) are performed. Generation of metabolites by MetaTox is based on the fragments datasets, which describe transformations of substrates structures to a metabolites structure. We added three new classes of biotransformation reactions: Dehydrogenation, Glutathionation, and Hydrolysis, and now metabolite generation for 15 most frequent classes of xenobiotic’s biotransformation reactions are available. MetaTox calculates the probability of formation of generated metabolite — it is the integrated assessment of the biotransformation reactions probabilities and their sites using the algorithm of PASS (http://way2drug.com/passonline). The prediction accuracy estimated by the leave-one-out cross-validation (LOO-CV) procedure calculated separately for the probabilities of biotransformation reactions and their sites is about 0.9 on the average for all reactions.

b-Bilene hydrochlorides are shown to be improved intermediates for the synthesis of metallo-isoporphyrins in enhanced yields (28% vs. 6%). Several new diamagnetic zinc(II) and a novel paramagnetic copper(II) isoporphyrin salts were also obtained using this approach. Metal-free isoporphyrins were also isolated. In vitro studies using human carcinoma HEp2 cells show that all metallo-isoporphyrins accumulate within cells and localize partially in the mitochondria. The zinc-isoporphyrins were found to be moderately phototoxic while the copper complex showed the lowest phototoxicity, maybe as a result of its paramagnetic nature.