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Daru : Journal of Faculty of Pharmacy,... May 2015Saffron (Crocus sativus) is an extensively used food additive for its color and taste. Since ancient times this plant has been introduced as a marvelous medicine... (Review)
Review
Saffron (Crocus sativus) is an extensively used food additive for its color and taste. Since ancient times this plant has been introduced as a marvelous medicine throughout the world. The wide spectrum of saffron pharmacological activities is related to its major constituents including crocin, crocetin and safranal. Based on several studies, saffron and its active ingredients have been used as an antioxidant, antiinflammatory and antinociceptive, antidepressant, antitussive, anticonvulsant, memory enhancer, hypotensive and anticancer. According to the literatures, saffron has remarkable therapeutic effects. The protective effects of saffron and its main constituents in different tissues including brain, heart, liver, kidney and lung have been reported against some toxic materials either natural or chemical toxins in animal studies.In this review article, we have summarized different in vitro and animal studies in scientific databases which investigate the antidotal and protective effects of saffron and its major components against natural toxins and chemical-induced toxicities. Due to the lake of human studies, further investigations are required to ascertain the efficacy of saffron as an antidote or a protective agent in human intoxication.
Topics: Animals; Antidotes; Crocus; Humans; In Vitro Techniques; Plant Extracts; Protective Agents
PubMed: 25928729
DOI: 10.1186/s40199-015-0112-y -
Journal of Intensive Care Medicine 2006The proper use of antidotes in the intensive care setting when combined with appropriate general supportive care may reduce the morbidity and mortality associated with... (Review)
Review
The proper use of antidotes in the intensive care setting when combined with appropriate general supportive care may reduce the morbidity and mortality associated with severe poisonings. The more commonly used antidotes that may be encountered in the intensive care unit (N-acetylcysteine, ethanol, fomepizole, physostigmine, naloxone, flumazenil, sodium bicarbonate, octreotide, pyridoxine, cyanide antidote kit, pralidoxime, atropine, digoxin immune Fab, glucagon, calcium gluconate and chloride, deferoxamine, phytonadione, botulism antitoxin, methylene blue, and Crotaline snake antivenom) are reviewed. Proper indications for their use and knowledge of the possible adverse effects accompanying antidotal therapy will allow the physician to appropriately manage the severely poisoned patient.
Topics: Antidotes; Critical Care; Critical Illness; Humans; Poisoning; Practice Guidelines as Topic
PubMed: 16946442
DOI: 10.1177/0885066606290386 -
Biomaterials May 2023Alcohol intoxication causes serious diseases, whereas current treatments are mostly supportive and unable to convert alcohol into nontoxic products in the digestive...
Alcohol intoxication causes serious diseases, whereas current treatments are mostly supportive and unable to convert alcohol into nontoxic products in the digestive tract. To address this issue, an oral intestinal-coating coacervate antidote containing acetic acid bacteria (AAB) and sodium alginate (SA) mixture was constructed. After oral administration, SA reduces absorption of ethanol and promotes the proliferation of AAB, and AAB converts ethanol to acetic acid or carbon dioxide and water by two sequential catalytic reactions in the presence of membrane-bound alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). In vivo study shows that the bacteria-based coacervate antidote can significantly reduce the blood alcohol concentration (BAC) and effectively alleviates alcoholic liver injury in mice. Given the convenience and effectiveness of oral administration, AAB/SA can be used as a promising candidate antidote for relieving alcohol-induced acute liver injury.
Topics: Mice; Animals; Antidotes; Blood Alcohol Content; Ethanol; Liver; Alcoholic Intoxication; Aldehyde Dehydrogenase
PubMed: 36878091
DOI: 10.1016/j.biomaterials.2023.122072 -
Emergencias : Revista de La Sociedad... Jun 2022To identify the most common problems related to use of N-acetylcysteine to reverse the toxic effects of paracetamol poisoning. (Observational Study)
Observational Study
OBJECTIVES
To identify the most common problems related to use of N-acetylcysteine to reverse the toxic effects of paracetamol poisoning.
MATERIAL AND METHODS
Retrospective descriptive observational study of clinical records for patients treated for paracetamol poisoning in 4 emergency departments during 3 years (2017-2019). We analyzed epidemiologic, clinical, and care variables, especially those related to the suitability and safety of using N-acetylcysteine as an antidote.
RESULTS
We included 332 cases of poisoning of 260 patients (78%) were over the age of 16 years, and 242 (73%) were female. Two hundred sixty-eight poisonings (81%) were the result of voluntary intake. The elimination half-life was determined in 20 cases (6%). Gastrointestinal decontamination was incorrectly prescribed on 39 occasions (28%). Treatment with the antidote was begun in 195 cases (58.7%). No serious clinical signs or symptoms were present in 282 cases (85%). The correlation of paracetamol levels in urine was stronger with the amount of drug ingested voluntarily (R2 = 0.23) than with accidental intake (R2 = 0.007). Predefined severity criteria were significantly related to reported dose ingested per body weight (P = .001) and the interval between intake and first medical assistance (P = .008).
CONCLUSION
Even though clear protocols are available to guide the use of antidote treatment in cases of paracetamol poisoning, variability in fundamental aspects of management is excessive.
Topics: Acetaminophen; Acetylcysteine; Adolescent; Antidotes; Emergency Service, Hospital; Female; Humans; Male; Retrospective Studies
PubMed: 35736523
DOI: No ID Found -
Bioorganic Chemistry Jul 2024Thrombosis leads to elevated mortality rates and substantial medical expenses worldwide. Human factor IXa (HFIXa) protease is pivotal in tissue factor (TF)-mediated...
Thrombosis leads to elevated mortality rates and substantial medical expenses worldwide. Human factor IXa (HFIXa) protease is pivotal in tissue factor (TF)-mediated thrombin generation, and represents a promising target for anticoagulant therapy. We herein isolated novel DNA aptamers that specifically bind to HFIXa through systematic evolution of ligands by exponential enrichment (SELEX) method. We identified two distinct aptamers, seq 5 and seq 11, which demonstrated high binding affinity to HFIXa (K = 74.07 ± 2.53 nM, and 4.93 ± 0.15 nM, respectively). Computer software was used for conformational simulation and kinetic analysis of DNA aptamers and HFIXa binding. These aptamers dose-dependently prolonged activated partial thromboplastin time (aPTT) in plasma. We further rationally optimized the aptamers by truncation and site-directed mutation, and generated the truncated forms (Seq 5-1t, Seq 11-1t) and truncated-mutated forms (Seq 5-2tm, Seq 11-2tm). They also showed good anticoagulant effects. The rationally and structurally designed antidotes (seq 5-2b and seq 11-2b) were competitively bound to the DNA aptamers and effectively reversed the anticoagulant effect. This strategy provides DNA aptamer drug-antidote pair with effective anticoagulation and rapid reversal, developing advanced therapies by safe, regulatable aptamer drug-antidote pair.
Topics: Aptamers, Nucleotide; Humans; Factor IXa; Antidotes; Dose-Response Relationship, Drug; Anticoagulants; Structure-Activity Relationship; Molecular Structure; SELEX Aptamer Technique
PubMed: 38776649
DOI: 10.1016/j.bioorg.2024.107463 -
Journal of Controlled Release :... Sep 2021Cyanide induces acute lethal poisoning resulting from inhibition of cytochrome c oxidase located in the complex IV (Complex IV) of mitochondria. However, current...
Cyanide induces acute lethal poisoning resulting from inhibition of cytochrome c oxidase located in the complex IV (Complex IV) of mitochondria. However, current therapies for cyanide poisoning using hydroxocobalamin and nitrous acid compounds remain a clinical issue. Here, we show that liposome-encapsulated methemoglobin (metHb@Lipo), nanosized biomimetic red blood cells, replicate the antidotal mechanism of nitrous acid compounds against cyanide poisoning, achieving superior efficacy and fast action with no adverse effects. The structure of metHb@Lipo, which consists of concentrated methemoglobin in its aqueous core and a lipid membrane resembling the red blood cell membrane, provides favorable characteristics as a cyanide antidote, such as binding properties and membrane permeability. Upon cyanide exposure, metHb@Lipo maintained the mitochondrial function in PC12 cells, resulting in a cell viability comparable to treatment with nitrous acid compounds. In a mouse model of cyanide poisoning, metHb@Lipo treatment dramatically improved mortality with a rapid recovery from the symptoms of cyanide poisoning compared to treatment with nitrous acid compounds. Furthermore, metHb@Lipo also possesses satisfactory pharmacokinetic properties without long-term bioaccumulation and toxicity. Our findings showed a novel concept to develop drugs for cyanide poisoning and provide a promising possibility for biomimetic red blood cell preparations for pharmaceutical applications.
Topics: Animals; Antidotes; Cyanides; Erythrocytes; Liposomes; Methemoglobin; Mice; Rats
PubMed: 34273418
DOI: 10.1016/j.jconrel.2021.07.015 -
Clinical Pediatrics Mar 1964
Topics: Antidotes; Poisoning; Toxicology
PubMed: 14127405
DOI: 10.1177/000992286400300310 -
Advanced Materials (Deerfield Beach,... Oct 2021Poisoning is a leading cause of admission to medical emergency departments and intensive care units. Supramolecular detoxification, which involves injecting...
Poisoning is a leading cause of admission to medical emergency departments and intensive care units. Supramolecular detoxification, which involves injecting supramolecular receptors that bind with toxins to suppress their biological activity, is an emerging strategy for poisoning treatment; it has few requirements and a broad application scope. However, it is still a formidable challenge to design supramolecular therapeutic materials as an antidote to macromolecular toxins, because the large size, flexible conformation, and presence of multiple and diverse binding sites of biomacromolecules hinder their recognition. Herein, a supramolecular antidote to macromolecular toxins is developed through the coassembly of macrocyclic amphiphiles, relying on heteromultivalent recognition between the coassembled components and toxic macromolecules. The coassembly of amphiphilic cyclodextrin and calixarene strongly and selectively captures melittin, a toxin studied herein; this imparts various therapeutic effects such as inhibiting the interactions of melittin with cell membranes, alleviating melittin cytotoxicity and hemolytic toxicity, reducing the mortality rate of melittin-poisoned mice, and mitigating damage to major organs. The use of the proposed antidote overcomes the limitation of supramolecular detoxification applicability to only small-molecular toxins. The antidote can also detoxify other macromolecular toxins as long as selective and strong binding is achieved because of the coassembling tunability.
Topics: Animals; Antidotes; Antimicrobial Cationic Peptides; Cell Membrane; Cell Survival; Cyclodextrins; HEK293 Cells; Hemolysis; Humans; Liver; Macromolecular Substances; Melitten; Mice; Spider Venoms
PubMed: 34418189
DOI: 10.1002/adma.202104310 -
BMC Biology Mar 2020CRISPR gene drive systems allow the rapid spread of a genetic construct throughout a population. Such systems promise novel strategies for the management of vector-borne...
BACKGROUND
CRISPR gene drive systems allow the rapid spread of a genetic construct throughout a population. Such systems promise novel strategies for the management of vector-borne diseases and invasive species by suppressing a target population or modifying it with a desired trait. However, current homing-type drives have two potential shortcomings. First, they can be thwarted by the rapid evolution of resistance. Second, they lack any mechanism for confinement to a specific target population. In this study, we conduct a comprehensive performance assessment of several new types of CRISPR-based gene drive systems employing toxin-antidote (TA) principles, which should be less prone to resistance and allow for the confinement of drives to a target population due to invasion frequency thresholds.
RESULTS
The underlying principle of the proposed CRISPR toxin-antidote gene drives is to disrupt an essential target gene while also providing rescue by a recoded version of the target as part of the drive allele. Thus, drive alleles tend to remain viable, while wild-type targets are disrupted and often rendered nonviable, thereby increasing the relative frequency of the drive allele. Using individual-based simulations, we show that Toxin-Antidote Recessive Embryo (TARE) drives targeting an haplosufficient but essential gene (lethal when both copies are disrupted) can enable the design of robust, regionally confined population modification strategies with high flexibility in choosing promoters and targets. Toxin-Antidote Dominant Embryo (TADE) drives require a haplolethal target gene and a germline-restricted promoter, but they could permit faster regional population modification and even regionally confined population suppression. Toxin-Antidote Dominant Sperm (TADS) drives can be used for population modification or suppression. These drives are expected to spread rapidly and could employ a variety of promoters, but unlike TARE and TADE, they would not be regionally confined and also require highly specific target genes.
CONCLUSIONS
Overall, our results suggest that CRISPR-based TA gene drives provide promising candidates for flexible ecological engineering strategies in a variety of organisms.
Topics: Antidotes; Antitoxins; CRISPR-Cas Systems; Gene Drive Technology; Genes, Essential; Haploinsufficiency; Models, Genetic
PubMed: 32164660
DOI: 10.1186/s12915-020-0761-2 -
Journal of Toxicology. Clinical... 1997
Topics: Antidotes; Diagnosis, Differential; Humans; Serotonin; Syndrome
PubMed: 9120895
DOI: 10.3109/15563659709001197