Natural Toxic Substances Research Articles

Mechanistic Insights into Nitrite Degradation by Metabolites of L. plantarum A50: An LC-MS-Based Untargeted Metabolomics Analysis

Nitrites are universally acknowledged natural toxic substances that frequently lead to poisoning in humans and animals. During fermentation, certain microorganisms utilize a portion of the nitrogen element and reduce nitrates to nitrites through specific metabolic pathways. In this study, a highly effective lactic acid bacterial strain, Lactiplantibacillus plantarum A50, was isolated and screened from alfalfa silage for its remarkable ability to degrade nitrites. L. plantarum A50 exhibits exceptional nitrite removal capacity, with a degradation rate of 99.06% within 24 h. Furthermore, L. plantarum A50 demonstrates normal growth under pH values ranging from 4 to 9 and salt concentrations of 5%, displaying excellent tolerance to acidity, alkalinity, and salinity. Additionally, it undergoes fermentation using various carbon sources. Within the first 6–12 h of culture, L. plantarum A50 primarily achieves nitrite degradation through non-acidic processes, resulting in a degradation rate of 82.67% by the 12th hour. Moreover, the metabolites produced by L. plantarum A50 exhibit a synergistic interaction with acidity, leading to a nitrite degradation rate of 98.48% within 24 h. Notably, both L. plantarum A50 and MRS broth were found to degrade nitrites. Consequently, a non-targeted metabolomic analysis using LC-MS was conducted to identify 342 significantly different metabolites between L. plantarum A50 and MRS broth. Among these, lipids and lipid-like molecules, organic acids and derivatives, organic oxygen compounds, and organoheterocyclic compounds emerged as the main constituents. Lipids and lipid-like molecules, derivatives of glucose and galactose, amino acids and their derivatives, as well as organoheterocyclic compounds, are likely to play a role in nitrite elimination. Through the enrichment analysis of differential metabolic pathways using KEGG, nine distinct pathways were identified. These pathways provide essential nutrients, maintain cellular structure and function, participate in substance transport, regulate metabolic activities, and enhance resistance against pathogenic microorganisms in L. plantarum A50.

Causative Substance and Time of Mortality Presented to Emergency Department Following Acute Poisoning: 2014-2018 National Emergency Department Information System (NEDIS)

Purpose: The purpose of this study was to investigate the cause of acute fatal poisoning and the time of death by analyzing the National Emergency Department Information System (NEDIS) of South Korea. Methods: The NEDIS data from 2014 to 2018 excluding non-medical visits were used for this study. The patients with acute poisoning were extracted using diagnostic codes. The toxic substances were classified into pharmaceuticals, pesticides, gases, artificial poisonous substances, and natural toxic substances. Patients were classified according to the time of death, place of death, and region. In each case, the most causative substances of poisoning were identified. Results: There were 380,531 patients including poisoning-related diagnoses, of which 4,148 (1.1%) died, and the WHO age-standardized mortality rate was 4.8 per 100,000. Analysis of 2,702 death patients whose primary diagnosis was acute poisoning, the most common cause of poisoning death was pesticides (62%), followed by therapeutic drugs, gas, and artificial toxic substances. Herbicides were the most common pesticides at 64.5%. The proportion of mortality by time, hyperacute (<6 h) 27.9%, acute (6-24 h) 32.6%, subacute (1-7 d) 29.7%, and delayed period (>7 d) were 9.8%. Conclusion: This study suggests that the most common cause of poisoning death was pesticides, and 60% of deaths occurred within 24 hours. The 71% of mortality from pesticides occurred within 6-24 hours, but mortality from gas was mostly within 6 hours. According to the geographic region, the primary cause of poisoning death was varied to pesticides or pharmaceuticals.

Herbal Medicine Must Be Treated with Care—A Case Report on Aconitine

Pathologists usually only request a screening for natural toxic substances if plant material has been observed during autopsy or if there exists a hint in the police investigation file. This situation is aggravated by the fact that most toxins are not covered by typical immunoassays and gas chromatography–mass spectrometry (GC–MS) profiling systems. In addition, only a few forensic toxicological libraries based on liquid chromatography coupled to high-resolution tandem mass spectrometry (LC–HRMS/MS) exist. In the following case, femoral blood and urine were applied to systematic toxicological analysis (STA). However, the concentrations determined in blood did not lead to death. Consequently, a liquid chromatography high-resolution tandem mass spectrometry (LC–HRMS/MS) screening approach was applied. Aconitine was quantitated in all specimens taken during autopsy and urine and bile fluid screened for aconitine metabolites. Aconitine, jesaconitine, hypaconitine, and mesaconitine were found in the root piece collected from the duodenum. Apart from aconitine, no other alkaloids were detected in the urine or in the femoral blood sample. The highest concentrations of aconitine were found in gastric content (55.2 μg/mL), bile fluid (11.7 μg/mL), and liver (9.14 μg/g), and least in femoral blood (0.15 μg/mL) and cerebrospinal fluid (0.07 μg/mL). The liver/peripheral blood ratio amounted to 61 L/kg and indicated that aconitine undergoes postmortem redistribution. During our metabolism investigation, we found 3-dehydrogen-aconitine in the urine and bile fluid sample and N-deethyl-aconitine only in the bile fluid sample. If the routine GC–MS screening approach does not come up with a toxin, then LC–HRMS/MS profiling could represent the method of choice. In this case aconitine was identified. The concentrations determined were compared to those reported in literature and clearly indicate that the deceased died due to an aconitine overdose.

Biokinetics and biotransformation of paralytic shellfish toxins in different tissues of Yesso scallops, Patinopecten yessoensis

Paralytic shellfish toxins (PSTs) are a group of natural toxic substances often found in marine bivalves. Accumulation, anatomical distribution, biotransformation and depuration of PSTs in different tissues of bivalves, however, are still not very well understood. In this study, we investigated biokinetics and biotransformation of PSTs in six different tissues, namely gill, mantle, gonad, adductor muscle, kidney, and digestive gland, in Yesso scallops Patinopecten yessoensis exposed to a toxic strain of dinoflagellate Alexandrium pacificum. High daily accumulation rate (DAR) was recorded at the beginning stage of the experiment. Most of the PSTs in toxic algae ingested by scallops were retained and the toxicity level of PSTs in scallops exceeded the regulatory limit within 5 days. At the late stage of the experiment, however, DAR decreased obviously due to the removal of PSTs. Fitting results of the biokinetics model indicated that the amount of PSTs transferred from digestive gland to mantle, adductor muscle, gonad, kidney, and gill in a decreasing order, and adductor muscle, kidney, and gonad had higher removal rate than gill and mantle. Toxin profile in digestive gland was dominated by N-sulfocarbamoyl toxins 1/2 (C1/2), closely resembled that of the toxic algae. In contrast, toxin components in kidney were dominated by high-potency neosaxitoxin (NEO) and saxitoxin (STX), suggesting that the kidney be a major organ for transformation of PSTs.

Sediment as a Potential Pool for Lipophilic Marine Phycotoxins with the Case Study of Daya Bay of China.

Marine sediments can reserve many environmental pollutants. Lipophilic marine phycotoxins (LMPs) are natural toxic substances widespread in the marine environment; however, evidence of their existence in sediment is scarce. In the present study, in order to explore the occurrence and distribution characteristics of LMPs in sediment, surface sediment samples collected from a tropical area of Daya Bay (DYB) at different seasons, were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). According to the results, up to six toxin compounds were detected in sediment samples from DYB, OA and DTX1 had the highest levels, followed by PTX2, homo-YTX, AZA2, and GYM. Although AZA2 and GYM were found in most of the sediment, OA, DTX1, homo-YTX, and PTX2 were the predominant toxin compounds, and PTX2 was the most ubiquitous toxin in sediment. The spatial distribution of LMP components in the sediment fluctuated with sampling times, partially according to the physical–chemical parameters of the sediment. There are likely several sources for LMPs existing in surface sediments, but it is difficult to determine contributions of a specific toxin-source in the sediment. Therefore, marine sediments may be a toxin reservoir for LMPs accumulation in benthic organisms via food chains.

Personal Care Products Are Only One of Many Exposure Routes of Natural Toxic Substances to Humans and the Environment

The special issue “A Critical View on Natural Substances in Personal Care Products” is dedicated to addressing the multidisciplinary special challenges of natural ingredients in personal care products (PCP) and addresses also environmental exposure. In this perspective article, we argue that environmental exposure is probably not so much dominated by PCP use, but in many cases by direct emission from natural or anthropogenically managed vegetation, including agriculture. In support of this hypothesis, we provide examples of environmental fate and behaviour studies for compound classes that are either listed in the International Nomenclature of Cosmetics Ingredients (INCI) or have been discussed in a wider context of PCP applications and have been classified as potentially harmful to humans and the environment. Specifically, these include estrogenic isoflavones, the carcinogenic ptaquiloside and pyrrolizidine alkaloids, saponins, terpenes and terpenoids, such as artemisinin, and mycotoxins. Research gaps and challenges in the domains of human and environmental exposure assessment of natural products common to our currently rather separated research communities are highlighted.

Nutrients and natural toxic substances in commonly consumed Jerusalem artichoke (Helianthus tuberosus L.) tuber

This study determined nutrients, chemical contaminants, (insecticide residues and heavy metals), and natural toxic substances (nitrate, nitrite, cyanide, oxalate, phytate, and trypsin inhibitor) in tubers of Jerusalem artichokes—Kaentawan in the Thai language—grown in four major provinces in Thailand. They were purchased, prepared, homogenized, and freeze-dried for further analysis using standard methods. All Kaentawan samples contained considerable amounts of fructans and dietary fiber (15.4±0.2gand3.2±0.8g/100gfresh weight [FW], respectively), as well as potassium and iron (339±61and0.32±0.05mg/100gFW, respectively). All samples had very low amounts of insecticide residues (37 compounds), cyanide, and trypsin inhibitor, as well as Pb, Cd, nitrate, and nitrite (0.82±0.09, 0.10±0.02, 1.9–17.5, and 0.01–0.24mgkg−1FW, respectively), in addition to oxalate and phytate (14±9and0.17±0.02mg/100gFW, respectively). This study’s data can be used for food composition databases and for safety consumption.

Binary Mixture Toxicity of AROCLOR 1248, Oleic Acid, and Elemental Sulfur to Vibrio fischeri Luminescence

The objective of this research was to evaluate the toxicity of the industial xenobiotic Aroclor 1248 (A) and natural origin substances~elemental sulfur (S80) and oleic acid (OA) and their binary mixtures to V. fischeri bioluminescence during the prolonged exposure time (up to 60 min). The bioluminescence quenching test was used to determine the toxic effects. Full factorial experiment design and multiple regression analysis and the comparison of binary mixture effect with the sum of effects of individual chemicals were used for the evaluation of combined effects of toxicants. The analysis of general trend of mixture toxicity to bioluminescence showed that mixture toxic effects were reversible up to 60 min. Data analysis revealed different joint effects, which were depended on mixture composition. S80 enhanced toxic effect of A and acted additively with synergistic interaction. Hydrophobic OA in mixture with A acted antagonistically and in mixture with sulfur caused an additive effect with antagonistic component of interaction. It was concluded that low concentrations of natural toxic substances present in environmental samples as mixtures of chemicals can define the toxicodynamic character of industrial xenobiotics.

Intragastric gavage with denatonium benzoate acutely induces neuronal activation in the solitary tract nucleus via the vagal afferent pathway.

Natural toxic substances have a bitter taste and their ingestion sends signals to the brain leading to aversive oral sensations. In the present study, we investigated chronological changes in c-Fos immunoreactivity in the nucleus tractus solitarius (NTS) to study the bitter taste reaction time of neurons in the NTS. Equal volumes (0.5 mL) of denatonium benzoate (DB), a bitter tastant, or its vehicle (distilled water) were administered to rats intragastrically. The rats were sacrificed at 0, 0.5, 1, 2, 4, 8, or 16 h after treatment. In the vehicle-treated group, the number of c-Fos-positive nuclei started to increase 0.5 h after treatment and peaked 2 h after gavage. In contrast, the number of c-Fos-positive nuclei in the DB-treated group significantly increased 1 h after gavage. Thereafter, the number of c-Fos immunoreactive nuclei decreased over time. The number of c-Fos immunoreactive nuclei in the NTS was also increased in a dose-dependent manner 1 h after gavage. Subdiaphragmatic vagotomy significantly decreased DB-induced neuronal activation in the NTS. These results suggest that intragastric DB increases neuronal c-Fos expression in the NTS 1 h after gavage and this effect is mediated by vagal afferent fibers.

Anticancer Effects of Niclosamide in Human Glioblastoma

Glioblastoma is a highly malignant, invariably fatal brain tumor for which effective pharmacotherapy remains an unmet medical need. Screening of a compound library of 160 synthetic and natural toxic substances identified the antihelmintic niclosamide as a previously unrecognized candidate for clinical development. Considering the cellular and interindividual heterogeneity of glioblastoma, a portfolio of short-term expanded primary human glioblastoma cells (pGBM; n = 21), common glioma lines (n = 5), and noncancer human control cells (n = 3) was applied as a discovery platform and for preclinical validation. Pharmacodynamic analysis, study of cell-cycle progression, apoptosis, cell migration, proliferation, and on the frequency of multipotent/self-renewing pGBM cells were conducted in vitro, and orthotopic xenotransplantation was used to confirm anticancer effects in vivo. Niclosamide led to cytostatic, cytotoxic, and antimigratory effects, strongly reduced the frequencies of multipotent/self-renewing cells in vitro, and after exposure significantly diminished the pGBMs' malignant potential in vivo. Mechanism of action analysis revealed that niclosamide simultaneously inhibited intracellular WNT/CTNNB1-, NOTCH-, mTOR-, and NF-κB signaling cascades. Furthermore, combinatorial drug testing established that a heterozygous deletion of the NFKBIA locus in glioblastoma samples could serve as a genomic biomarker for predicting a synergistic activity of niclosamide with temozolomide, the current standard in glioblastoma therapy. Together, our data advocate the use of pGBMs for exploration of compound libraries to reveal unexpected leads, for example, niclosamide that might be suited for further development toward personalized clinical application.

Mycotoxins Levels in Human Milk: A Menace to Infants and Children Health

Infants, especially newborns, are more susceptible to contaminants than adult humans because of their physiological immaturity. Synthetic or natural toxic substances, such as mycotoxins, can lead to acute intoxication episodes, as the example of aflatoxicosis. However, the long-term effects caused by exposure to low levels of these contaminants are of most concern to practitioners and public health authorities. Children's exposure to mycotoxins (and various other toxic compounds) may start immediately after conception, as many contaminants cross the placenta, and continues throughout life, entering the human body through food, water and air. Mycotoxins that offer higher risk to child health are aflatoxins B1 (AFB1), M1 (AFM1) and ochratoxin A (OTA), commonly present in foods consumed by children, such as milk and dairy products. Even breast milk can be a vehicle for the transfer of mycotoxins to babies, since the mycotoxins contained in food ingested by the mother may pass into her milk, continuing childhood exposure to these compounds, initiated in utero. This paper reviews levels reported on mycotoxins in human milk, the influence of maternal diet and the possible effects on children's health.

Veterinary drugs and food safety : a toxilogical approach.

Summary : To eat is to take a risk. Numerous natural toxic substances occur in foods, and such substances have not yet been examined in detail. Some are known, others not, and they may be very harmful (aflatoxins). Under these conditions, natural and synthetic compounds are not different from the toxi­ cological aspect. The use of veterinary drugs is no doubt beneficial, but it creates the proba­ bility of residues. Ten years ago the simple idea of zero tolerance was accep­ ted, but the development of analytical techniques led to its rejection. Residues exist, but always in small amounts and not necessarily toxic. From the aspect of toxicity, there must be no confusion between the toxicity of residual amounts and the toxicity of the actual drug for human or veterinary use : the doses acquired by ingestion or by administration are very different. The toxicological dimension of residues can be provided solely by scientific appreciation of their toxicity : this is their toxicological significance. Any dan­ ger has to be assessed by testing for chronic toxicity, where repetition of intake is the important factor (concept of regular ingestion). As a result of such assessment it is possible to define the tolerance which will guarantee the protection of the health of consumers. Of course, such tolerances have to be treated with caution. They merely serve to guide the correct and rational utili­ sation of medicaments of high quality, with adequate controls.