Toxicological Aspects Research Articles

Green Synthesized Nanomaterials: An Analysis of the Impact on Cellular Processes, Gene Regulation, and Epigenome

Green synthesis of nanoparticles has gained prominence in recent years as a cost-effective and environmentally sustainable approach. This green nanotechnology has diverse applications, and their potential impact on cellular processes needs to be thoroughly examined via nanomaterials. One of the major challenges in this field is the alleviation of oxidative damage, cytotoxicity, and genotoxicity induced by nanoparticles. Lately, research is more focused on analyzing the epigenetic effects including DNA methylation and histone modifications mediated through the alteration in microRNA expression that is influenced by nanoparticles. Due to their physical and chemical properties, these nanomaterials are extremely suitable carriers of targeted modifications in gene regulatory systems. Delivery of silencing RNAs and artificial transcription factors built on nanoparticles for modulating gene expression has been extensively reported in recent years. Studies on various cell lines have confirmed the downstream effects of these changes in gene expression, as demonstrated by the significant alteration in expression of proteins functional in a multitude of pathways, such as those associated with oxidative stress, cytoskeletal proteins, molecular chaperones, proteins involved in energy metabolic processes, and apoptosis and tumor-related proteins. This reshuffling of molecular expression has also been corroborated by investigations at genomic, transcriptomic, proteomic, and metabolomic levels. This chapter highlights the detailed mechanism of modulation of gene regulation and expression, and the cytological and molecular changes caused by these bionanomaterials. The toxicological aspects and biocompatibility impacts of these nanoparticles, which are of paramount importance while considering their biomedical and environmental applications, have also been outlined.

Illicit Drug Exposures Reported to the Poisons Information Centre Erfurt (2011 to 2020)

Because of significant changes in recent years, cases of illicit drug exposure reported to the Poisons Information Centre (PIC) Erfurt during the last 10 years were investigated. Retrospective analysis of above-mentioned cases from 2011 to 2020 according to substance classes, symptom severity, age groups, and gender. Cases of illicit drug exposure (4,963, 2.8% of all exposures) increased from 316 in 2011 to 614 in 2015, decreased to 514 in 2017, and rose again to 578 in 2019. In 2020, a drop to 549 cases was observed. The ratio of multiple to single drug exposure cases, however, increased from 1.0 to 1.7 in 2020. Cases of exposure to psychostimulants almost doubled from 168 in 2011 to 319 in 2020. Cases of exposure to new psychoactive substances (NPS) rose from 21 in 2011 to 126 in 2015 and fell to 16 in 2020. 320 cases (6.5%) of illicit drug exposures resulted in severe, 1902 cases (38.3%) in moderate and 2139 cases (43.1%) in minor or no symptoms. Age groups mainly involved were adults of middle age (72.7%) and unknown age (12.7%) as well as adolescents (12.1%). Men (69.9%) were more often involved than women (26.9%). Illicit drug exposures reported to the Poisons Information Centre (PIC) Erfurt discontinuously increased from 2011 to 2020 mainly by increase in mixed consumption. The intermittent decrease in 2016 and 2017 was caused by the fall of NPS exposures. Data of substance abuse from PICs could supplement official annual drug reports in aspects of Clinical Toxicology.

Medicinal plants used during Pregnancy and Childbirth in Baramulla District of Jammu and Kashmir, India

Background: Although medicinal plants have long been beneficial to women's health, understanding regarding their usage during pregnancy and childbirth is scarce. This is the first research of its kind in the study area, with the aim of documenting and preserving traditional knowledge of medicinal plants used during pregnancy and childbirth. Materials and Methods: Field surveys were carried out from August 2018 to December 2020 in Baramulla district of Jammu and Kashmir. Information was gathered through group discussions, field tours and personal interviews using standard questionnaire with the tribal people, traditional healers, midwives and pregnant women. The data collected was analyzed through Use value (UV) and Informant Consensus factor (ICF). Results: A total of 60 medicinal plant species belonging to 56 genera and 30 families were reported to be commonly utilized by women for treating various health issues during pregnancy and childbirth. The Lamiaceae was found to be the most prevalent plant family, with leaves being the most regularly used plant part. Of all other methods of remedy preparation decoction was reported to be the most preferred. Childbirth had the highest ICF value and the most widely accepted medicinal plants were Cydonia oblonga, Malva neglecta, Thymus linearis, Geranium wallichianum, Achyranthes aspera, Taraxacum officinale and Ajuga bracteosa as per the Use Value. Conclusion: The current findings highlight the need for more in-depth research into the phytochemical, pharmacological, and toxicological aspects of commonly used medicinal plants for pregnancy and childbirth related health issues in order to provide reliable information to primary users and to develop novel drugs. Keywords: Medicinal plants, Pregnancy, Childbirth, Baramulla, J&K

Enantia chlorantha and its Multiple Therapeutic Virtues: A Mini Review

Enantia chlorantha is a plant commonly employed traditionally in phytotherapy to treat various ills. It has been a source of interest for many scientific works due to its exceptional properties, thus in the essence of highlighting the most pertinent outcome of the results obtained, this review had as objective to present the plant, its traditional uses, its composition, and multitude of exploitable virtues. Nevertheless, the adverse effect and the toxicological aspect constituting a limit to its use in conventional medicine, was also treated.

Coffee Leaves: An Upcoming Novel Food?

Unlike those of coffee beans, the healthy properties of coffee leaves have been overlooked for a long time, even if they are consumed as a beverage by local communities of several African countries. Due to the presence of xanthines, diterpenes, xanthones, and several other polyphenol derivatives as main secondary metabolites, coffee leaves might be useful to prevent many daily disorders. At the same time, as for all bioactive molecules, careless use of coffee leaf infusions may be unsafe due to their adverse effects, such as the excessive stimulant effects on the central nervous system or their interactions with other concomitantly administered drugs. Moreover, the presence of some toxic diterpene derivatives requires careful analytical controls on manufactured products made with coffee leaves. Accordingly, knowledge about the properties of coffee leaves needs to be increased to know if they might be considered a good source for producing new supplements. The purpose of the present review is to highlight the biosynthesis, metabolism, and distribution of the 4 main classes of secondary metabolites present in coffee leaves, their main pharmacological and toxicological aspects, and their main roles in planta. Differences in coffee leaf chemical composition depending on the coffee species will also be carefully considered.

Safety Evaluation of Doogh, a Traditional Iranian Dairy Product, in Khuzestan, Iran: A Cross-Sectional Study on Microbiological, Chemical and Toxicological Aspects

Safety Evaluation of Doogh, a Traditional Iranian Dairy Product, in Khuzestan, Iran: A Cross-Sectional Study on Microbiological, Chemical and Toxicological Aspects

Non-Heating Alternating Magnetic Field Nanomechanical Stimulation of Biomolecule Structures via Magnetic Nanoparticles as the Basis for Future Low-Toxic Biomedical Applications.

The review discusses the theoretical, experimental and toxicological aspects of the prospective biomedical application of functionalized magnetic nanoparticles (MNPs) activated by a low frequency non-heating alternating magnetic field (AMF). In this approach, known as nano-magnetomechanical activation (NMMA), the MNPs are used as mediators that localize and apply force to such target biomolecular structures as enzyme molecules, transport vesicles, cell organelles, etc., without significant heating. It is shown that NMMA can become a biophysical platform for a family of therapy methods including the addressed delivery and controlled release of therapeutic agents from transport nanomodules, as well as selective molecular nanoscale localized drugless nanomechanical impacts. It is characterized by low system biochemical and electromagnetic toxicity. A technique of 3D scanning of the NMMA region with the size of several mm to several cm over object internals has been described.

Ethnomedicinal Use, Phytochemistry, and Pharmacology of Xylocarpus granatum J. Koenig.

The mangrove plants are the potential sources of foods and remedies for people living in the forests and nearby communities. Xylocarpus granatum J. Koenig is traditionally used to treat various diseases including diarrhea, cholera, dysentery, fever, malaria, and viral infections, among others. To summarize critically the taxonomy, ethnomedicinal, phytochemistry, and pharmacological activities of X. granatum, information was collected from different databases. An up-to-date search (till June 2020) was carried out with the help of various scientific web resources from databases such as PubMed, Science Direct, Google Scholar, and various patent offices (e.g., WIPO, CIPO, and USPTO) using the keywords “Xylocarpus granatum” and then paired with ethnomedicinal use and phytochemical, phytochemistry, and pharmacological activity (in vitro, ex vivo, and in vivo studies). Findings revealed that seeds, fruits, stem bark, leaf, and twigs of X. granatum exhibited a wide range of key phytochemicals including limonoids, phragmalin, limonoid-based alkaloids, mexicanolides, protolimonoids, flavonols, and lactones. The plant possessed potent antioxidant, anticancer, antidiabetic, antimicrobial, antimalarial, antifeedant, and neuroprotective activities. No clinical studies have been reported in the databases. Ethnomedicinal assessment indicated the application of X. granatum in various fields of medical science specially to treat various human ailments, and this was attributed to the presence of enormous alkaloids as confirmed by pharmacological studies. However, to understand the mechanism of action in-depth studies are required. In view of these findings, more research is necessary to explore and characterize the chemical compounds and toxicological aspects of this medicinal mangrove plant. Overall, it can be stated that X. granatum may be one of the hopeful medicinal herbs for the treatment of various diseases in human beings.

Catunaregam spinosa (Thunb.) Tirveng: A Review of Traditional Uses, Phytochemistry, Pharmacological Activities, and Toxicological Aspects.

Catunaregam spinosa (Thunb.) Tirveng. (Syn. Randia dumetorum (Retz.) Lam.), belonging to the Rubiaceae family, is distributed in south Asian countries. It is used as a traditional medicine to treat gastrointestinal and hepatic problems and as an anti-inflammatory and antimicrobial agent. The main aim of this review is to collect and analyze the available scientific information on traditional uses, phytochemistry, and pharmacological activities of C. spinosa. The scientific information related to C. spinosa was collected from various resources and databases such as SciFinder, Scopus, PubMed, and other databases. C. spinosa was found to be an important crude drug of the traditional medicinal systems such as Ayurveda. It was found to be used by the people of India as an alternative medicine, while the fruit of this plant was found to be used in dietary regimens as well. Active phytochemicals such as catunarosides, randianin, and several other saponins and triterpenoids possess various pharmacological activities such as anti-inflammatory, hepatoprotective, antibacterial, and immunomodulatory activities. Many studies have been performed to isolate the active compounds; however, there is a need for more activity-guided isolation studies. Various in vitro studies showed promising results but there are not many studies related to mechanism of actions using animal models. Hence, future studies on C. spinosa should focus on correlating the traditional uses with active phytoconstituents and modern pharmacological activities.

Ethnopharmacological, Phytochemical, Pharmacological, and Toxicological Review on Senna auriculata (L.) Roxb.: A Special Insight to Antidiabetic Property.

Avartaki (Senna auriculata (L.) Roxb. syn. Cassia auriculata L.; Family- Fabaceae ) is a traditional medicinal plant, widely used for the treatment of various ailments in Ayurveda and Siddha system of medicine in India. Almost all the parts of the plant, such as flowers, leaves, seeds, barks, and roots have been reported for their medicinal uses. Traditionally, it has been used in the treatment of diabetes, asthma, rheumatism, dysentery, skin disease, and metabolic disorders. The principle phytochemicals in Senna auriculata (L.) Roxb. are alkaloids, anthraquinone, flavone glycosides, sugar, saponins, phenols, terpenoids, flavonoids, tannins, steroids, palmitic acid, linoleic acid, benzoic acid 2-hydroxyl methyl ester, 1-methyl butyl ester, resorcinol, α-tocopherol-β-D-mannosidase, epicatechin, ferulic acid, quercetin-3-O-rutinoside, quercetin, proanthocyanidin B1. The extracts from its different parts and their isolated compounds possess a wide range of pharmacological activities such as antidiabetic, antioxidant, anti-inflammatory, antihyperlipidemic, hepatoprotective, nephroprotective, cardioprotective, anti-atherosclerotic, anticancer, antimutagenic, antimicrobial, antiulcer, antipyretic, anthelmintic, immunomodulatory, antifertility, anti-venom, and anti-melanogenesis. The toxicological findings from preclinical studies ensured the safety of the plant, but comprehensive clinical studies are required for the safety and efficacy of the plant in humans. The current review article aimed to provide up-to-date information about Senna auriculata (L.) Roxb. covering its ethnomedicinal, phytochemical, pharmacological, and toxicological aspects with special emphasis on its clinical implications in diabetes.

Phytochemistry, Pharmacology, and Toxicology of Datura Species—A Review

Datura, a genus of medicinal herb from the Solanaceae family, is credited with toxic as well as medicinal properties. The different plant parts of Datura sp., mainly D. stramonium L., commonly known as Datura or Jimson Weed, exhibit potent analgesic, antiviral, anti-diarrheal, and anti-inflammatory activities, owing to the wide range of bioactive constituents. With these pharmacological activities, D. stramonium is potentially used to treat numerous human diseases, including ulcers, inflammation, wounds, rheumatism, gout, bruises and swellings, sciatica, fever, toothache, asthma, and bronchitis. The primary phytochemicals investigation on plant extract of Datura showed alkaloids, carbohydrates, cardiac glycosides, tannins, flavonoids, amino acids, and phenolic compounds. It also contains toxic tropane alkaloids, including atropine, scopolamine, and hyoscamine. Although some studies on D. stramonium have reported potential pharmacological effects, information about the toxicity remains almost uncertain. Moreover, the frequent abuse of D. stramonium for recreational purposes has led to toxic syndromes. Therefore, it becomes necessary to be aware of the toxic aspects and the potential risks accompanying its use. The present review aims to summarize the phytochemical composition and pharmacological and toxicological aspects of the plant Datura.

Forensic Analysis of Illicit Drugs and Novel Psychoactive Substances in Wastewater: A review of Toxicological, Chemical and Microbiological Aspects

Wastewater-based epidemiology has emerged as a new analytical strategy for monitoring licit and illicit drug use in a population by measuring the levels of biomarkers in wastewater. The main concept of this approach is that chemical substances ingested by the population will be excreted in urine and feces, which will be discarded into the sewage network and may accumulate at the wastewater treatment plant. Several licit and illicit substances such as ethanol, nicotine, cocaine, amphetamine, methamphetamine and morphine have been investigated and reported in wastewater in worldwide. In recent years, this approach has also been explored for environmental monitoring of novel psychoactive substances (NPS) as well, since analyses of wastewater represent a fast and cost-effective way to evaluate collectively drug intake in a given population served by a sewage network. In this paper, a comprehensive and interdisciplinary review of the forensic, toxicological, chemical and microbiological aspects of the analysis of “traditional” drugs of abuse and NPS in wastewater and examples of applications reported in recently published papers is provided. Wastewater analysis is a very promising strategy in monitoring drug use in the context of Forensic Chemistry and Toxicology, and has been implemented by many researchers in the analysis of drugs of abuse, as supported by many recent literature reports.

Toxicological aspects of cannabinoid, pesticide and metal levels detected in light Cannabis inflorescences grown in Italy

Recently, the cultivation of light Cannabis, with a total THC content less than 0.6%, has been encouraged due to its industrial and therapeutic potential. This has increased the consumption of hemp for both smoking purposes and food preparation. Even so, Cannabis inflorescences are not subject to EU regulations and standards provided for food and tobacco products. A study was carried out on thirty-one inflorescences samples, collected in different Italian regions, in order to determine cannabinoids, pesticides and metals and to evaluate the exposure of consumers to contaminants and ensure a safe consumption. Contents of THC were always below 0.5%, while CBD ranged between 0.3 and 8.64%. The determination of 154 pesticides showed that 87% of the samples contained fungicides and insecticides in the range 0.01–185 μg/g. The most found are spinosad and cyprodinil. The concentration of metals ranged from 1 to more than 100 μg/g and As, Cd, Co, Cr, Hg, Cu, Mo, Ni and V exceeded the regulatory US limits for inhaled Cannabis products, while Pb exceeded them for both oral and inhaled products. These contaminants are intrinsically toxic and may affect public health. Actions are needed to establish regulatory measures and reduce the adverse effects caused by contaminants in Cannabis.

Bioconversion of sugarcane vinasse into fungal biomass protein and its potential use in fish farming

The intensification of pisciculture operation requires the provision of an adequate supply of good quality fish feed. Many commercial feeds consist in fishmeal or soybean meal-based formulations, but they constitute costly protein sources. Hence, dietary transition from conventional fish ingredients towards fungi protein sources produced from vinasse could address concern about both fish feed cost and the detrimental environmental effects of distillery waste disposal. This work investigated the nutritional and toxicological aspects of Aspergillus sp. V2 grown on vinasse to be used as a possible fish feed. Proximate analysis of biomass obtained from 50% (v/v) residue supplemented with 2.0 g/L (NH4)2H2PO4 revealed a total proteins content (34.0%), fat (4.7%), ash (15.8%), crude fiber (4.0%), moisture (0.3%) and carbohydrate (45.2%) within acceptable levels for commercial fish diets. The biomass protein composition was similar to soybean meal, containing all the essential amino acids (EAAs) for fish feeding. Finally, total aflatoxins level was 6.8 ± 0.2 µg per kg of dry weight, which does not exceed the permissible levels established for feedstuffs. These findings provide evidence that biomass of Aspergillus sp. V2 produced from vinasse could meet the nutritional requirements for use in fish diet, reducing economic pressures for the pisciculture and distilleries.

A REVIEW ON TOXICITY OF SNUHI (EUPHORBIA NERIFOLIA LINN.)

Snuhi (Euphorbia nerifolia Linn.) is a widely known poisonous medicinal plant in Ayurveda. It is categorized un- der Sthavara Upavisha. In Ayurveda, Upavisha is the group of drugs that are less toxic and not so lethal but pro- duces certain toxic symptoms on consumption or administration. Snuhi is one among the Upavisha and a well- known plant in the Indian system of medicine. In the Ayurveda concept, it is believed that toxic material may be useful in various diseases if it is administered properly and similarly even a drug if not administered properly be- comes an acute poison. The present review article highlights overall information about the plant Snuhi, its toxico- logical aspect, management, medico-legal aspect. Keywords: Snuhi, Upavisha, Toxicological aspect

Polyphenols as anticancer agents: Toxicological concern to healthy cells.

Polyphenols are a group of diverse chemical compounds present in a wide range of plants. Various biological properties such as antiallergic, antiviral, antibacterial, anticarcinogenic, antiinflammatory, antithrombotic, vasodilatory, and hepatoprotective effect of different polyphenols have been reported in the scientific literature. The major classes of polyphenols are flavonoids, stilbenoids, lignans, and polyphenolic acids. Flavonoids are a large class of food constituents comprising flavones, isoflavanones, flavanones, flavonols, catechins, and anthocyanins sub-classes. Even with seemingly broad biological activities, their use is minimal clinically. Among the other concurrent problems such as limited bioavailability, rapid metabolism, untargeted delivery, the toxicity associated with these polyphenols has been a topic of concern lately. These polyphenols have been reported to result in different forms of toxicity that include organ toxicity, genotoxicity, mutagenicity, cytotoxicity, etc. In the present article, we have tried to unravel the toxicological aspect of these polyphenols to healthy cells. Further high-quality studies are needed to establish the clinical efficacy and toxicology concern leading to further exploration of these polyphenols.

Various Solvent Effects on Phytochemical Screening and Gas Chromatography–mass Spectroscopy Analysis of Tephrosia Villosa Leaf Extract Mass

Introduction: Plants produce various chemicals to protect themselves; but recent studies proved that many phytochemicals can also protect humans against infectious diseases. The present study was conducted to identify and characterize the phytoconstituents and gas chromatography–mass spectroscopy (GCMS) analysis of petroleum ether, chloroform, ethyl acetate, ethanol, methanol, and aqueous extract of leaves of Tephrosia villosa (L.) Pers. of family Fabaceae. Materials and Method: The leaf extracts were subjected to qualitative screening for primary and secondary metabolites as per standard methods; further, GC–MS analysis was carried out for the identification of secondary metabolites. Result: Preliminary phytochemical screening of leaf extract of T. villosa showed positive result for alkaloids, flavonoids and triterpenoids, saponins, glycosides, gum and mucilages, and fixed oils in methanolic extract which is followed by aqueous extract. In quantitative analysis, the highest amount of phenolic content was obtained in aqueous extract, tannin in petroleum ether, and flavonoids and saponins in ethyl acetate. GC–MS analysis of leaf extract revealed the presence of 53 bioactive phytochemical compounds. Conclusion: It can be concluded that the species contain effective phytochemical compounds, need further research on toxicological aspects to develop a safe drug.

Identification of a Series of N-Methylpyridine-2-carboxamides as Potent and Selective Inhibitors of the Second Bromodomain (BD2) of the Bromo and Extra Terminal Domain (BET) Proteins.

Domain-specific BET bromodomain ligands represent an attractive target for drug discovery with the potential to unlock the therapeutic benefits of antagonizing these proteins without eliciting the toxicological aspects seen with pan-BET inhibitors. While we have reported several distinct classes of BD2 selective compounds, namely, GSK620, GSK549, and GSK046, only GSK046 shows high aqueous solubility. Herein, we describe the lead optimization of a further class of highly soluble compounds based upon a picolinamide chemotype. Focusing on achieving >1000-fold selectivity for BD2 over BD1 ,while retaining favorable physical chemical properties, compound 36 was identified as being 2000-fold selective for BD2 over BD1 (Brd4 data) with >1 mg/mL solubility in FaSSIF media. 36 represents a valuable new in vivo ready molecule for the exploration of the BD2 phenotype.

Dietary Flavonoids: Cardioprotective Potential with Antioxidant Effects and Their Pharmacokinetic, Toxicological and Therapeutic Concerns.

Flavonoids comprise a large group of structurally diverse polyphenolic compounds of plant origin and are abundantly found in human diet such as fruits, vegetables, grains, tea, dairy products, red wine, etc. Major classes of flavonoids include flavonols, flavones, flavanones, flavanols, anthocyanidins, isoflavones, and chalcones. Owing to their potential health benefits and medicinal significance, flavonoids are now considered as an indispensable component in a variety of medicinal, pharmaceutical, nutraceutical, and cosmetic preparations. Moreover, flavonoids play a significant role in preventing cardiovascular diseases (CVDs), which could be mainly due to their antioxidant, antiatherogenic, and antithrombotic effects. Epidemiological and in vitro/in vivo evidence of antioxidant effects supports the cardioprotective function of dietary flavonoids. Further, the inhibition of LDL oxidation and platelet aggregation following regular consumption of food containing flavonoids and moderate consumption of red wine might protect against atherosclerosis and thrombosis. One study suggests that daily intake of 100 mg of flavonoids through the diet may reduce the risk of developing morbidity and mortality due to coronary heart disease (CHD) by approximately 10%. This review summarizes dietary flavonoids with their sources and potential health implications in CVDs including various redox-active cardioprotective (molecular) mechanisms with antioxidant effects. Pharmacokinetic (oral bioavailability, drug metabolism), toxicological, and therapeutic aspects of dietary flavonoids are also addressed herein with future directions for the discovery and development of useful drug candidates/therapeutic molecules.

Toxicological Aspect of Fatal Methamphetamine

Drug addiction has become a worldwide problem and the leading cause of death. The global problem of addiction and drug abuse is responsible for hundreds of deaths every year. It affects not only individual users, but also their families and communities. The current study, presents the fatality of some cases caused by the complications brought about the presence of methamphetamine and other abused drugs. It has been a drug of abuse in the past and is still gaining popularity as a recreational drug because of its much longer excitatory duration of more than three hours and its biotransformation to amphetamine, the active metabolite. In present postmortem cases methamphetamine and other combined drugs have issue in cardiac major health problems and poisoning-related deaths. Many postmortem cases found positive to methamphetamine and amphetamine or combined with other drugs include different narcotics/ stimulants drugs such as : benzodiazepines, THC, opium, and lyrica. The toxic effects of methamphetamine can explain increasing reports of heart failure and consequently death in young abusers. As this recognition may prove to be of some forensic value to clarify the death in methamphetamine abusers.