Palytoxin, isolated from a zoanthid of the genus Palythoa, is the most potent marine toxin known. Intoxication by palytoxin leads to vasoconstriction, hemorrhage, ataxia, muscle weakness, ventricular fibrillation, pulmonary hypertension, ischemia and death. Palytoxin and its numerous derivatives (congeners) may enter the food chain and accumulate mainly in fishes and crabs, causing severe human intoxication and death following ingestion of contaminated products. Furthermore, toxic effects in individuals exposed via inhalation or skin contact to marine aerosol in coincidence with Ostreopsis blooms, have been reported. Blooms of the benthic dinoflagellate Ostreopsis cf. ovata are a concern in the Mediterranean Sea, since this species produces a wide range of palytoxin-like compounds listed among the most potent marine toxins. Thus, the formerly unsuspected broad distribution of the benthic dinoflagellate Ostreopsis spp. has recently posed a problem of risk assessment for human health. Palytoxin has a strong potential for toxicity in humans and animals, and currently this toxin is of great concern worldwide. This review summarized and discussed the pharmacology and toxicology data of palytoxin and its congeners, including their cytotoxicity, human and animal toxicities. Moreover, the risk assessment and their control strategies including prevention and treatment assays were evaluated.
- MeSH
- akrylamidy chemie farmakokinetika toxicita MeSH
- bicyklické sloučeniny heterocyklické chemie toxicita MeSH
- hodnocení rizik metody MeSH
- jedy žahavců chemie farmakokinetika toxicita MeSH
- lidé MeSH
- mořské toxiny chemie farmakokinetika toxicita MeSH
- pyrany chemie toxicita MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Polymer drug carriers that are based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers have been widely used in the development and synthesis of high-molecular-weight (HMW) drug delivery systems for cancer therapy. In this study, we compared linear (Mw ~27kDa, Rh ~4nm) and non-degradable star (Mw ~250kDa, Rh ~13nm) HPMA copolymer conjugates bearing anthracycline antibiotic doxorubicin (DOX) bound via pH-sensitive hydrazone bond. We determined the in vitro and in vivo toxicity of both conjugates and their maximum tolerated dose (MTD). We also compared their anti-tumour activity in mouse B-cell leukaemia (BCL1) and a mouse T-cell lymphoma (EL4) model. We found that MTD was higher for the linear conjugate (85mgDOX/kg) and lower for the star conjugate (22.5mgDOX/kg). An evaluation of the intestinal barrier integrity using FITC-dextran as a gut permeability tracer proved that no pathology was caused by the MTD of either conjugate. However, free DOX showed some damage to the gut barrier. The therapy of BCL1 leukaemia by both of the polymeric conjugates using the MTD or its fraction (i.e., equitoxic dosage) showed better results in the case of the star conjugate. On the other hand, treatment of EL4 lymphoma seemed to be more efficient when the linear conjugate was used. We suppose that the anti-cancer treatment of solid tumours and leukaemias requires different types of drug conjugates. We hypothesise that the most suitable HPMA copolymer-DOX conjugate for the treatment of solid tumours should have an HMW structure with increased Rh that would be stable for three to four days after the conjugate administration and then rapidly disintegrate in the short polymer chains, which are excretable from the body by glomerular filtration. On the other hand, the treatment of leukaemia requires a drug conjugate with a long circulation half-life. This would provide an active drug, whilst slowly degrading to excretable fragments.
- MeSH
- akrylamidy chemie farmakokinetika terapeutické užití toxicita MeSH
- antibiotika antitumorózní * chemie farmakokinetika terapeutické užití toxicita MeSH
- dendrimery chemie farmakokinetika terapeutické užití toxicita MeSH
- doxorubicin chemie farmakokinetika terapeutické užití toxicita MeSH
- játra účinky léků patologie MeSH
- kostní dřeň účinky léků patologie MeSH
- maximální tolerovaná dávka MeSH
- molekulová hmotnost MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory krev farmakoterapie metabolismus MeSH
- nosiče léků * chemie farmakokinetika terapeutické užití toxicita MeSH
- slezina účinky léků patologie MeSH
- střeva metabolismus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
This review briefly describes the origin, chemistry, molecular mechanism of action, pharmacology, toxicology, and ecotoxicology of palytoxin and its analogues. Palytoxin and its analogues are produced by marine dinoflagellates. Palytoxin is also produced by Zoanthids (i.e. Palythoa), and Cyanobacteria (Trichodesmium). Palytoxin is a very large, non-proteinaceous molecule with a complex chemical structure having both lipophilic and hydrophilic moieties. Palytoxin is one of the most potent marine toxins with an LD50 of 150 ng/kg body weight in mice exposed intravenously. Pharmacological and electrophysiological studies have demonstrated that palytoxin acts as a hemolysin and alters the function of excitable cells through multiple mechanisms of action. Palytoxin selectively binds to Na(+)/K(+)-ATPase with a Kd of 20 pM and transforms the pump into a channel permeable to monovalent cations with a single-channel conductance of 10 pS. This mechanism of action could have multiple effects on cells. Evaluation of palytoxin toxicity using various animal models revealed that palytoxin is an extremely potent neurotoxin following an intravenous, intraperitoneal, intramuscular, subcutaneous or intratracheal route of exposure. Palytoxin also causes non-lethal, yet serious toxic effects following dermal or ocular exposure. Most incidents of palytoxin poisoning have manifested after oral intake of contaminated seafood. Poisonings in humans have also been noted after inhalation, cutaneous/systemic exposures with direct contact of aerosolized seawater during Ostreopsis blooms and/or through maintaining aquaria containing Cnidarian zoanthids. Palytoxin has a strong potential for toxicity in humans and animals, and currently this toxin is of great concern worldwide.
- MeSH
- akrylamidy chemie izolace a purifikace toxicita MeSH
- Dinoflagellata patogenita fyziologie MeSH
- Haplorrhini MeSH
- korálnatci patogenita fyziologie MeSH
- králíci MeSH
- krysa rodu rattus MeSH
- LD50 MeSH
- lidé MeSH
- morčata MeSH
- mořské řasy patogenita fyziologie MeSH
- mořské toxiny chemie izolace a purifikace toxicita MeSH
- myši MeSH
- otrava z mlžů patofyziologie MeSH
- psi MeSH
- sodíko-draslíková ATPasa metabolismus MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- morčata MeSH
- myši MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Acrylamide is a potential carcinogen. Several toxicological studies have demonstrated its genotoxic carcinogenicity in animals thus indicating potential human health risks. It is present in several carbohydrate-rich foods on frying, baking and roasting at temperatures higher than 120 °C. Most of the acrylamide dietary exposure has its origin in potato products, coffee, bakery products and chocolate. Acrylamide forms in potato products during their processing, retail, catering and home preparation.
- MeSH
- akrylamidy * analýza chemie otrava škodlivé účinky toxicita MeSH
- dávka bez pozorovaného nepříznivého účinku MeSH
- hodnocení rizik MeSH
- lidé MeSH
- Maillardova reakce * MeSH
- manipulace s potravinami * MeSH
- potraviny klasifikace škodlivé účinky toxicita MeSH
- primární prevence MeSH
- průmysl zpracování potravin MeSH
- Check Tag
- lidé MeSH
WHO technical report series, ISSN 0512-3054 959
viii, 105 s. : tab. ; 24 cm
- MeSH
- akrylamidy toxicita MeSH
- arsen toxicita MeSH
- furany toxicita MeSH
- hodnocení rizik MeSH
- kontaminace potravin analýza MeSH
- perchloráty toxicita MeSH
- rtuť toxicita MeSH
- trichotheceny toxicita MeSH
- Konspekt
- Potravinářský průmysl
- NLK Obory
- toxikologie
- zemědělství a potravinářství
- NLK Publikační typ
- publikace WHO
