Hasil untuk "Toxicology. Poisons"

T. Lidsky, J. Schneider

D. Gunnell, M. Eddleston, M. Phillips et al.

BackgroundEvidence is accumulating that pesticide self-poisoning is one of the most commonly used methods of suicide worldwide, but the magnitude of the problem and the global distribution of these deaths is unknown.MethodsWe have systematically reviewed the worldwide literature to estimate the number of pesticide suicides in each of the World Health Organisation's six regions and the global burden of fatal self-poisoning with pesticides. We used the following data sources: Medline, EMBASE and psycINFO (1990–2007), papers cited in publications retrieved, the worldwide web (using Google) and our personal collections of papers and books. Our aim was to identify papers enabling us to estimate the proportion of a country's suicides due to pesticide self-poisoning.ResultsWe conservatively estimate that there are 258,234 (plausible range 233,997 to 325,907) deaths from pesticide self-poisoning worldwide each year, accounting for 30% (range 27% to 37%) of suicides globally. Official data from India probably underestimate the incidence of suicides; applying evidence-based corrections to India's official data, our estimate for world suicides using pesticides increases to 371,594 (range 347,357 to 439,267). The proportion of all suicides using pesticides varies from 4% in the European Region to over 50% in the Western Pacific Region but this proportion is not concordant with the volume of pesticides sold in each region; it is the pattern of pesticide use and the toxicity of the products, not the quantity used, that influences the likelihood they will be used in acts of fatal self-harm.ConclusionPesticide self-poisoning accounts for about one-third of the world's suicides. Epidemiological and toxicological data suggest that many of these deaths might be prevented if (a) the use of pesticides most toxic to humans was restricted, (b) pesticides could be safely stored in rural communities, and (c) the accessibility and quality of care for poisoning could be improved.

R. O. Recknagel

During the past 20 years, study of the fatty liver induced by carbon tetrachloride has passed through 2 periods of revolutionary change, and at the present time a third revolutionary change is taking place. The dominant notion guiding most of the thinking before 1948 was that toxic and nutritional fatty liver disease could be understood in terms of failure in transport of fatty acids as phospholipids. As quantitative analyses of whole body phospholipid and neutral lipid metabolism became available through application of radioisotope technology, it became possible by 1953 to conclude that fatty acids were not transported in the plasma as phospholipids. For the next 6 years work in this field was dominated by the mitochondrial hypothesis. Carbon tetrachloride was thought to damage the liver cell mitochondria. It was suggested that lipid accumulation was due to a failure of normal pathways of lipid oxidation, and that death of the liver cells resulted from interruption in energy-transducing mechanisms. By 1959 this hypothesis also proved untenable since accumulation of triglycerides and degeneration of the hepatocellular endoplasmic reticulum preceeded mitochondrial degeneration by many hours. The major contribution of the work of this period was the introduction into the study of experimental hepatic toxicology of methods of biochemical cytology. A second revolutionary change took place in 1960. It became evident that carbon tetrachloride poisoning leads rapidly to cessation of movement of large quantities of triglycerides from the liver to the plasma. The blockade of hepatic triglyceride secretion by carbon tetrachloride accounts for the characteristic fatty liver. Earlier studies of rates of replacement of the different moieties of the plasma lipoproteins had demonstrated that low-density lipoprotein triglycerides were replaced much faster than the protein moiety. This work, as well as more recent studies combining use of the isolated, perfused liver with methods for separation of plasma protein and lipoprotein fractions, has made possible a most important new insight into the nature of hepatic triglyceride secretion. The latter can best be understood as a dual mechanism. One part of the mechanism involves hepatic biosynthesis of the various moieties of plasma low-density lipoproteins, coupling of these to form definitive lipoprotein molecules, and their extrusion to the plasma compartment. An auxiliary mechanism provides for re-entry into the system of triglyceride-free lipoprotein apoprotein. Movement of triglycerides from liver to plasma depends largely on the continuous functioning of the second, or auxiliary arm of the cycle. The knowledge that hepatic triglyceride secretion involves a dual mechanism has provided a powerful new guide for the analysis of mechanisms underlying fatty liver disease. In the case of carbon tetrachloride poisoning, the rapid onset of liver triglyceride accumulation most probably results mainly from cessation in function of the auxiliary coupling phase of hepatic triglyceride secretion, and less significantly from a breakdown in hepatic protein synthesis. During this period, ca . 1960 to 1965, highly provocative experimental findings led to an attempt to rationalize the hepatocellular necrosis and the triglyceride accumulation of carbon tetrachloride poisoning in terms of massive discharge of the sympathetic nervous system. The main evidence regarding the pathogenesis of hepatocellular necrosis was based on the observation that rats whose spinal cord had been divided were remarkably immune to the toxic agent. A review of the evidence does not support the contention that hepatocellular necrosis is a consequence of catecholamine discharge. The catecholamine hypothesis suggested that hepatic lipid accumulation is due to an oversupply of fatty acids mobilized from peripheral adipose tissue depots. Activation of the hypophyseal-adrenocortical axis has also been invoked in support of the peripheral oversupply hypothesis. A central requirement of this hypothesis must be that if oversupply of fatty acids is to be invoked as a significant factor in the pathogenesis of fatty liver, then the oversupply must be of sufficient magnitude and duration to account for the time course of the hepatic lipid accumulation. From this point of view the evidence offered in support of the peripheral oversupply hypothesis is not convincing. In particular, for carbon tetrachloride poisoning, at a time when liver triglycerides are increasing rapidly, there is no increase in flux of fatty acids through the plasma compartment. The most recent work in this field has inaugurated a third revolution in the study of carbon tetrachloride hepatotoxicity. Its essential feature is the recognition that carbon tetrachloride toxicity depends on cleavage of the carbon-tochlorine bond. At the same time, the long-held view that the toxic action of carbon tetrachloride resided in its effectiveness as a lipid solvent has finally been discarded. An important link has been established between the metabolism of carbon tetrachloride and the peroxidative decomposition of cytoplasmic membrane structural lipids. Sufficient data are not yet available to decide whether the latter effect is a major or minor consequence of the metabolism of carbon tetrachloride. The important point is that study of this problem has reached the organic chemical level of organization. This augurs well for the immediate future, which should witness further interesting new developments in the study of haloalkane toxicity.

Lei Wu, Lei Wu, Congli Yang et al.

BackgroundMushroom poisoning, a form of foodborne intoxication, poses serious life-threatening risks in severe cases. Russula subnigricans, a rare but highly toxic species, warrants particular attention due to its unique symptom profile and clinical manifestations.MethodsWe conducted a retrospective analysis of 103 patients with confirmed highly suspected Russula subnigricans poisoning admitted to the Affiliated Hospital of Yunnan University between 2020 and 2024. Data encompassed epidemiological characteristics, clinical manifestation, laboratory findings, and treatment outcomes.ResultsPatients were predominantly middle-aged (61.2%) and from Yunnan Province (93.2%), with most poisonings (93.2%) resulting from Self-picking. Symptom onset was rapid (median latency, 2.4 h), primarily featuring gastrointestinal, cardiovascular, and rhabdomyolysis-related manifestations. Laboratory findings revealed high rates of hepatotoxicity (97.1%) and myocardial injury (85.4%). A combination of conventional therapy and blood purification was employed in 60.2% of cases, yielding favorable outcomes. After treatment at Yunnan University Affiliated Hospital, the final clinical outcomes were as follows: 91 patients (88.3%) recovered and were discharged.ConclusionRussula subnigricans poisoning is characterized by severe multi-organ toxicity. The adjunctive application of blood purification in combination with conventional therapy appears associated with improved clinical outcomes, although no specific antidote exists. Future research should focus on elucidating toxin mechanisms and toxicokinetics to guide targeted treatment and prevention strategies.

Anna M.L. Klompen, Kevin Ferro, Cassandra G. Kempf et al.

Cnidarians possess a cell-based venom system in the form of nematocytes or “stinging cells” that are found across various tissues. The scattered distribution of these venom-containing cells makes isolation difficult, particularly for proteomic studies. These challenges can be circumvented in laboratory systems with efficient culturing conditions and robust molecular resources for downstream validation, such as exists for Hydra and Nematostella. The colonial hydrozoan Hydractinia symbiolongicarpus is an established laboratory model and an emerging candidate for functional studies of the venom system. Here, we present a proteome derived from a fluorescence-activated cell sorted cell population of developing and mature nematocytes from an established Hydractinia transgenic line. We detected a total of 8,470 proteins, of which 2,232 could be statistically quantified across two different fluorescence-activated cell sorting gating strategies. We found that 165 proteins were enriched within a more lenient, low-cell bias strategy while 760 proteins were enriched using a more stringent gating strategy with greater predicted cell viability. We compared this dataset to a previously assembled nematocyst-enriched transcriptome, as well as two different single-cell RNA-sequencing datasets for Hydractinia, to validate the enrichment of protein candidates in the nematocyte lineage. Furthermore, we evaluated orthologous clusters shared between our Hydractinia proteome, a well-established nematocyst proteome from Hydra, and nematocyst-enriched proteomes from two other cnidarians. Through these comparisons, we revealed substantial shared clusters across these four cnidarian species as well as multiple hydrozoan-specific clusters. Overall, our proteomic analysis provides an integral, complementary resource to the established molecular and laboratory tools available in Hydractinia, advancing its utility as a functional venom systems model.

J. Bajgar

Rita Sofia Vilela, Francisco Pina-Martins, Célia Ventura

<i>Alternaria</i> mycotoxins represent a significant and emerging concern in the field of food safety due to their widespread occurrence in diverse food and feed commodities, including cereals, tomatoes, oilseeds, and dried fruits. Among these, alternariol (AOH), alternariol monomethyl ether (AME), tenuazonic acid (TeA), and altertoxin-I (ATX-I) are the most frequently detected, often co-occurring at varying concentrations, thereby increasing the complexity of exposure and risk assessment. The gastrointestinal tract (GIT) is a crucial target of these toxins, as well as the liver, particularly considering its detoxifying role. Nevertheless, despite being a source of possible gastrointestinal and hepatic toxicity, there is still scarce data on the toxicokinetics of <i>Alternaria</i> toxins, on their mode of action, and respective toxic effects. To date, in vitro studies have shown that different <i>Alternaria</i> mycotoxins exhibit diverse toxicological effects, which may be dependent on their chemical structure. AOH and ATX-I have shown genotoxicity and cytotoxicity, mainly through interaction with the DNA and apoptosis, respectively. Tentoxin (TEN) has displayed hepatotoxic potential via impairment of detoxification pathways, and altenuene (ALT) has revealed lower toxicity. In vivo, AME and ATX-II revealed genotoxicity, while AOH and ATX-I showed context-dependent variability in their effects. Altogether, this review emphasizes that there is still a great lack of knowledge on these mycotoxins and an urgent need for more comprehensive toxicological and occurrence data to support proper risk assessment and, ultimately, regulatory decision-making.

Jesús Eduardo Vega-Tamayo, Esteban de Jesús Alcantar-Orozco, Ramiro Arturo Mendoza-Ramírez et al.

Abstract Cnidarian venom toxins have attracted increasing interest due to their remarkable molecular diversity and pharmacological potential. Omics technologies - such as genomics, transcriptomics, proteomics, and metabolomics - have facilitated the identification of toxin-encoding genes, providing key insights into their evolutionary trajectories and structure-function relationships, which are essential for understanding their mechanisms of action and therapeutic value. Nevertheless, the functional validation and production of complex toxins remain challenging, particularly for those requiring intricate folding or post-translational modifications. Recombinant expression has emerged as a strategic alternative to traditional purification methods, enabling controlled toxin production and the possibility of modifying their properties through genetic engineering. In parallel, advances in synthetic biology, such as cell-free protein synthesis systems, are creating new opportunities for toxin characterization, although their industrial scalability remains limited. Computational tools, including those based on artificial intelligence, are beginning to support the prioritization and functional analysis of toxins identified through omics approaches. This review provides an updated overview of the advances, limitations, and future perspectives in cnidarian toxin research, highlighting their promising role as a valuable source of bioactive compounds with therapeutic and biotechnological applications.

Alevtina Y. Grishanova, Maria L. Perepechaeva

Pharmacological compounds can disrupt glucose homeostasis, leading to impaired glucose tolerance, hyperglycemia, or newly diagnosed diabetes, as well as worsening glycemic control in patients with pre-existing diabetes. Traditional risk factors alone cannot explain the rapidly growing global incidence of diabetes. Therefore, prevention of insulin resistance could represent an effective strategy. Achieving this goal requires a deeper understanding of the mechanisms underlying the development of insulin resistance, with particular attention to the aryl hydrocarbon receptor (AhR). AhR, a transcription factor functioning as a xenobiotic sensor, plays a key role in various molecular pathways regulating normal homeostasis, organogenesis, and immune function. Activated by a range of exogenous and endogenous ligands, AhR is involved in the regulation of glucose and lipid metabolism as well as insulin sensitivity. However, current findings remain contradictory regarding whether AhR activation exerts beneficial or detrimental effects. This narrative review summarizes recent studies exploring the role of the AhR pathway in insulin secretion and glucose homeostasis across different tissues, and discusses molecular mechanisms involved in this process. Considering that several drugs act as AhR ligands, the review also compares how these ligands affect metabolic pathways of glucose and lipid metabolism and insulin sensitivity, producing either positive or negative effects.

Darlan Quinta Brito, Tathyana Benetis Piau, Carlos Henke-Oliveira et al.

With the escalating frequency and intensity of global wildfires driven by climate change, fire retardants (FRs) have become essential tools in wildfire management. Despite their widespread use, the environmental safety of newer FR formulations—particularly in relation to aquatic ecosystems and developmental toxicity—remains insufficiently understood. In particular, their effects on fish embryos, which represent a sensitive and ecologically important life stage, are poorly characterized. This study investigated the acute toxicity of three commercially available FRs—N-Borate, N-Phosphate+, and N-Phosphate-—on early life stages of zebrafish (<i>Danio rerio</i>), based on an OECD 236 Fish Embryo Toxicity (FET) test. Notably, N-Phosphate- FR exhibited significant toxicity with a 96 h LC50 of 60 mg/L (0.0055%), while N-Borate (>432 mg/L, >0.032%) and N-Phosphate+ (>1181 mg/L, >0.08%) showed substantially lower toxicity. Sublethal effects, including reduced yolk sac absorption and yolk sac darkening, were observed across all FRs, highlighting potential developmental disruptions. The elevated toxicity of N-Phosphate- FR likely stems from its surfactant content. These findings reveal variations in the acute toxicity of different FR formulations, emphasizing the need for ecotoxicological assessments to guide the selection of safer FRs for wildfire management and to protect aquatic biodiversity. The results highlight the importance of incorporating developmental endpoints in FR risk assessments and provide foundational data for regulatory decisions regarding FR application near aquatic habitats. Further research is necessary to elucidate the mechanisms underlying observed effects and to evaluate cross-species toxicity at environmentally relevant concentrations.

Zsolt Ráduly, L. Szabó, Anett Madar et al.

Due to Earth’s changing climate, the ongoing and foreseeable spreading of mycotoxigenic Aspergillus species has increased the possibility of mycotoxin contamination in the feed and food production chain. These harmful mycotoxins have aroused serious health and economic problems since their first appearance. The most potent Aspergillus-derived mycotoxins include aflatoxins, ochratoxins, gliotoxin, fumonisins, sterigmatocystin, and patulin. Some of them can be found in dairy products, mainly in milk and cheese, as well as in fresh and especially in dried fruits and vegetables, in nut products, typically in groundnuts, in oil seeds, in coffee beans, in different grain products, like rice, wheat, barley, rye, and frequently in maize and, furthermore, even in the liver of livestock fed by mycotoxin-contaminated forage. Though the mycotoxins present in the feed and food chain are well documented, the human physiological effects of mycotoxin exposure are not yet fully understood. It is known that mycotoxins have nephrotoxic, genotoxic, teratogenic, carcinogenic, and cytotoxic properties and, as a consequence, these toxins may cause liver carcinomas, renal dysfunctions, and also immunosuppressed states. The deleterious physiological effects of mycotoxins on humans are still a first-priority question. In food production and also in the case of acute and chronic poisoning, there are possibilities to set suitable food safety measures into operation to minimize the effects of mycotoxin contaminations. On the other hand, preventive actions are always better, due to the multivariate nature of mycotoxin exposures. In this review, the occurrence and toxicological features of major Aspergillus-derived mycotoxins are summarized and, furthermore, the possibilities of treatments in the medical practice to heal the deleterious consequences of acute and/or chronic exposures are presented.

Mu-zi Zhang, Ming Li, Rixin Wang et al.

ABSTRACT Ammonia can easily form in intensive culture systems due to ammonification of uneaten food and animal excretion, which usually brings detrimental health effects to fish. However, little information is available on the mechanisms of the detrimental effects of ammonia stress and mitigate means in fish. In this study, the four experimental groups were carried out to test the response of yellow catfish to ammonia toxicity and their mitigation through taurine: group 1 was injected with NaCl, group 2 was injected with ammonium acetate, group 3 was injected with ammonium acetate and taurine, and group 4 was injected taurine. The results showed that ammonia poisoning could induce ammonia, glutamine, glutamate and malondialdehyde accumulation, and subsequently lead to blood deterioration (red blood cell, hemoglobin and serum biochemical index reduced), oxidative stress (superoxide dismutase and catalase activities declined) and immunosuppression (lysozyme, 50% hemolytic complement, total immunoglobulin, phagocytic index and respiratory burst reduced), but the exogenous taurine could mitigate the adverse effect of ammonia poisoning. In addition, ammonia poisoning could induce up‐regulation of antioxidant enzymes (Cu/Zn‐SOD, CAT, GPx and GR), inflammatory cytokines (TNF, IL‐1 and IL‐8) and apoptosis (p53, Bax, caspase 3 and caspase 9) genes transcription, suggesting that cell apoptotic and inflammation may relate to oxidative stress. This result will be helpful to understand the mechanism of aquatic toxicology induced by ammonia in fish. HIGHLIGHTSAmmonia poisoning induces oxidative stress and inflammation.High blood ammonia level leads cell apoptotic.The exogenous taurine could mitigate the adverse effect.

Wayne Litakerb, Marina Montresorc, S. Murrayd et al.

Lingyun Wang, Xueguang Ran, Hao Tang et al.

G. D. Albano, Ginevra Malta, Corinne La Spina et al.

The use of illicit and non-illicit substances is widespread in suicides. The toxicological data may help in understanding the mechanism of death. This systematic review aimed to analyze autopsies related to suicides by consuming poison, focusing on the correlation between substance use and the country of origin to create an alarm bell to indicate that suicide maybe attempted and prevent it. The systematic review was conducted according to the PRISMA guidelines, with the primary objective of identifying autopsies conducted in cases of suicide by consuming poison in specific geographic areas. Significant differences in substances were observed between low-income and Western countries that confirm previous literature data. In rural areas and Asian countries, most suicides by consuming poison involve the use of pesticides, such as organophosphates and carbamates. In Western countries, illicit drugs and medically prescribed drugs are the leading cause of suicide by self-poisoning. Future research should shed light on the correlation between social, medical, and demographic characteristics and the autopsy findings in suicides by self-poisoning to highlight the risk factors and implement tailored prevention programs worldwide. Performing a complete autopsy on a suspected suicide by self-poisoning could be essential in supporting worldwide public health measures and policy makers. Therefore, complete autopsies in such cases must be vigorously promoted.

Sophie Giacomazzi, N. Cochet

B. Mégarbane, M. Oberlin, J. Alvarez et al.

Background Poisoning is one of the leading causes of admission to the emergency department and intensive care unit. A large number of epidemiological changes have occurred over the last years such as the exponential growth of new synthetic psychoactive substances. Major progress has also been made in analytical screening and assays, enabling the clinicians to rapidly obtain a definite diagnosis. Methods A committee composed of 30 experts from five scientific societies, the Société de Réanimation de Langue Française (SRLF), the Société Française de Médecine d’Urgence (SFMU), the Société de Toxicologie Clinique (STC), the Société Française de Toxicologie Analytique (SFTA) and the Groupe Francophone de Réanimation et d’Urgences Pédiatriques (GFRUP) evaluated eight fields: (1) severity assessment and initial triage; (2) diagnostic approach and role of toxicological analyses; (3) supportive care; (4) decontamination; (5) elimination enhancement; (6) place of antidotes; (7) specificities related to recreational drug poisoning; and (8) characteristics of cardiotoxicant poisoning. Population, Intervention, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE ® methodology. Results The SRLF-SFMU guideline panel provided 41 statements concerning the management of pharmaceutical and recreational drug poisoning. Ethanol and chemical poisoning were excluded from the scope of these recommendations. After two rounds of discussion and various amendments, a strong consensus was reached for all recommendations. Six of these recommendations had a high level of evidence (GRADE 1±) and six had a low level of evidence (GRADE 2±). Twenty-nine recommendations were in the form of expert opinion recommendations due to the low evidences in the literature. Conclusions The experts reached a substantial consensus for several strong recommendations for optimal management of pharmaceutical and recreational drug poisoning, mainly regarding the conditions and effectiveness of naloxone and N -acetylcystein as antidotes to treat opioid and acetaminophen poisoning, respectively.

E. Olsen, J. O'Donnell, C. Mattson et al.

Kratom (Mitragyna speciosa), a plant native to Southeast Asia, contains the alkaloid mitragynine, which can produce stimulant effects in low doses and some opioid-like effects at higher doses when consumed (1). Use of kratom has recently increased in popularity in the United States, where it is usually marketed as a dietary or herbal supplement (1). Some studies suggest kratom has potential for dependence and abuse (1,2). As of April 2019, kratom was not scheduled as a controlled substance. However, since 2012, the Food and Drug Administration has taken a number of actions related to kratom, and in November 2017 issued a public health advisory*; in addition, the Drug Enforcement Administration has identified kratom as a drug of concern. During 2011–2017, the national poison center reporting database documented 1,807 calls concerning reported exposure to kratom (3). To assess the impact of kratom, CDC analyzed data from the State Unintentional Drug Overdose Reporting System (SUDORS). CDC funds 32 states and the District of Columbia to abstract into SUDORS detailed data on unintentional and undetermined intent opioid overdose deaths from death certificates and medical examiner and coroner reports, including postmortem toxicology results.† Although kratom is not an opioid, overdose deaths involving kratom (including nonopioid overdose deaths) are included in SUDORS.§ Although postmortem toxicology testing varies in scope among medical examiners and coroners, SUDORS records all substances detected on postmortem toxicology testing, along with overdose-specific circumstances. CDC analyzed overdose deaths in which kratom was detected on postmortem toxicology testing and deaths in which kratom was determined by a medical examiner or coroner to be a cause

Masashi Ohe

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), broke out in late 2019 to become a serious global threat to human health. The recent, rapid development of vaccines against COVID-19 represents a huge achievement and offers hope of ending the global pandemic. However, only a fraction of the world population can receive vaccines as of yet. As a result, large numbers of people continue to be exposed and become infected. Therefore, finding effective and low-priced drugs against COVID-19 and carrying out clinical trials of these drugs remain a worthwhile and beneficial pursuit.

Izabel Vianna Villela, Miriana da Silva Machado

New Approach Methodologies (NAMs) are any non-animal-based approaches that can provide information in the context of chemical hazard and safety assessment. The goal is to develop information with equivalent or better scientific quality and relevance than that provided by traditional animal models. Starting with ethical issues, these approaches are gaining regulatory relevance in different global agencies. Since 2008, with the enactment of the Arouca Law—the first Brazilian legislation dedicated to laboratory animals, NAMs are gathering pace in Brazil’s regulations. Specific regulations from different sectors include the acceptance of these new methods. However, some regulation is controversial about what is needed to address specific toxicological endpoints. The resulting regulatory uncertainty induces companies to keep on adopting the traditional methods, slowing NAM’s development in the country. This work brings a perspective on the regulatory acceptance of NAMs in Brazilian Legislation for the registration of pharmaceuticals, medical devices, food/supplements, and agrochemical products. This text discusses the main issues of NAM adoption for each specific regulation. Therefore, legal acceptance of NAMs results in Brazil is still a process in progress. A collective effort including regulators, industry, contract research organizations (CROs), and the academic environment is needed to build regulatory confidence in the use of NAMs.