Browsing by Subject "Toxicity"
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- PublicationOpen AccessAssessing chemical toxicity of ionic liquids on Vibrio fischeri: Correlation with structure and composition(Pergamon – Elsevier Science Ltd, 2016-04-11) Hidalgo, Juana M; García Montalbán, Mercedes; Salinas Hidalgo, María Dolores; Collado-González, Mar; Díaz Baños, F. Guillermo; Víllora Cano, Gloria; Biología Celular e HistologíaOne of the most important properties of the ionic liquids (ILs) is their non-volatility. However, they are wide soluble in water. For this reason, they can be released to aquatic ecosystems and to contribute to water pollution. Nevertheless, toxicological data related to ionic liquids is scarce in literature because of the great number of possible ionic liquids synthesized. The present work reports the toxicity of twenty-nine imidazolium-, pyridinium- and ammonium-based ionic liquids towards the luminescent bacteria Vibrio fischeri. Some of the effects analyzed on the toxicity have been the type of anion, the length of the alkyl chain of the cation, the cation core and the presence of a functionalized side chain in the cation. These results have showed that the main influence on the toxicity of the ILs is the alkyl chain length. A Quantitative Structure-Activity Relationships (QSAR) method has been used to validate our results obtaining a very good agreement.
- PublicationOpen AccessCytotoxicity of Kuwait weathered lake crude oil on rat hepatocytes, a histological and ultrastructural study(Murcia : F. Hernández, 1998) Safer, A.M.; Meakins, R.; Akbar, L.; Abou-Salem, K.In the present study, the cytotoxic effects of Kuwaiti weathered crude oil and a potent carcinogen (DMBA) on rat liver cells were examined by light and electron microscopy at each of 4 sampling periods after the start of low dosing (0.5 and 0.2 mg/kg) of feed. Such effects were compared with those of olive oil and uncontaminated food-exposed controls. The results confirm a pronounced cell damage which statistically not significant (p<0.05). In crude oil, the organelle changes were variable and highly comparable to that of DMBA. The nuclei were mostly disintegrated while the cell showed demarcation of cytoplasmic vacuolization, lipid augmentation, and mitochondrial aberrations. The latter showed a remarkable association with the rough endoplasmic reticulum and lipid droplets, and appeared as decayed and diffused structures within the cell matrix. There was no comparable changes in the hepatocytes of animals fed with uncontaminated food except for the formation of lipid droplets in the olive oil-fed groups. Although the animals food was contaminated with Kuwaiti weathered oil formed in 1991 were exposed to extreme seasonal temperatures, yet the residues of such oil led to severe histopathological alterations in the liver cells which were similar to those of DMBA-treated cells. There is the need to pay attention to potential hazardous effects of the crude oil on environments.
- PublicationOpen AccessGemtuzumab ozogamicin in acute myeloid leukemia: efficacy, toxicity, and resistance mechanisms — a systematic review(MDPI, 2024-01-17) Collados Ros, Aurelia; Muro, Manuel; Legaz Pérez, Isabel; Ciencias SociosanitariasAcute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with chromosomal rearrangements and multiple gene mutations and the impairment of normal hematopoiesis. Current efforts to improve AML outcomes have focused on developing targeted therapies that may allow for improved antileukemic effects while reducing toxicity significantly. Gemtuzumab ozogamicin (GO) is one of the most thoroughly studied molecularly targeted therapies in adults. GO is a monoclonal antibody against CD33 IgG4 linked to the cytotoxic drug calicheamicin DMH. The use of GO as a chemotherapeutic agent is not generalized for all patients who suffer from AML, particularly for those whose health prevents them from using intensive conventional chemotherapy, in which case it can be used on its own, and those who have suffered a first relapse, where its combination with other chemotherapeutic agents is possible. This systematic review aimed to comprehensively evaluate GO, focusing on its molecular structure, mode of action, pharmacokinetics, recommended dosage, resistance mechanisms, and associated toxicities to provide valuable information on the potential benefits and risks associated with its clinical use. A systematic review of eight scientific articles from 2018 to 2023 was conducted using PRISMA analysis. The results showed that GO treatment activates proapoptotic pathways and induces double-strand breaks, initiating DNA repair mechanisms. Cells defective in DNA repair pathways are susceptible to GO cytotoxicity. GO has recommended doses for newly diagnosed CD33+ AML in combination or as a single agent. Depending on the treatment regimen and patient status, GO doses vary for induction, consolidation, and continuation cycles. Multidrug resistance (MDR) involving P-glycoprotein (P-gp) is associated with GO resistance. The overexpression of P-gp reduces GO cytotoxicity; inhibitors of P-gp can restore sensitivity. Mitochondrial pathway activation and survival signaling pathways are linked to GO resistance. Other resistance mechanisms include altered pharmacokinetics, reduced binding ability, and anti-apoptotic mechanisms. GO has limited extramedullary toxicity compared to other AML treatments and may cause hepatic veno-occlusive disease (HVOD). The incidence of hepatic HVOD after GO therapy is higher in patients with high tumor burden. Hematological side effects and hepatotoxicity are prominent, with thrombocytopenia and neutropenia observed. In conclusion, GO’s reintroduction in 2017 followed a thorough FDA review considering its altered dose, dosing schedule, and target population. The drug’s mechanism involves CD33 targeting and calicheamicin-induced DNA damage, leading to apoptosis and resistance mechanisms, including MDR and survival signaling, which impact treatment outcomes. Despite limited extramedullary toxicity, GO is associated with hematological side effects and hepatotoxicity.
- PublicationOpen AccessIn vivo cellular uptake of bismuth ions from shotgun pellets(Murcia : F. Hernández, 2003) Stoltenberg, M.; Locht, L.; Larsen, Agnete; Jensen, D.Shotgun pellets containing bismuth (Bi) are widely used and may cause a rather intense exposure of some wild animals to Bi. A Bi shotgun pellet was implanted intramuscularly in the triceps surae muscle of 18 adult male Wistar rats. Another group of 9 animals had a Bi shotgun pellet implanted intracranially in the neocortex. Eight weeks to 12 months later the release of Bi ions was analysed by autometallography (AMG) of tissue sections from different organs (brain, spinal cord, kidney, liver, testes). In the group with intramuscular Bi shotgun pellets no AMG staining could be found for the first 2-4 months; 6 months after exposure Bi was traced in the kidney. Twelve months after the implantation the kidneys were heavily loaded and Bi was also traced in testosterone-producing Leydig cells, in glial cells and in neurons of brain and spinal cord. In the central nervous system (CNS) motor neurons were the most loaded. In rats with intracranially implanted shotgun pellets a massive uptake of Bi was observed involving both glia and neurons throughout the brain. The cells close to the shotgun pellet had the highest uptake. The animals showed a pronounced Bi uptake in the ependyma cells lining the ventricular system and in the cubic epithelia covering the choroid plexus. Dissemination of Bi ions to the rest of the body was demonstrated by AMG tracing of Bi accumulations in the tubular cells of the kidney. These findings emphasize that metallic Bi, including shotgun pellets, represents sites of intense Bi pollution if implanted or shot into a living organism, and further that such metallic Bi bodies, if they enter the CNS, cause a spread of Bi ions throughout it.
- PublicationEmbargoMercury accumulation, structural damages, and antioxidant and immune status changes in the Gilthead Seabream (Sparus aurata L.) exposed to methylmercury(Springer, 2016-02-23) Guardiola, F. A.; Chaves-Pozo, E.; Espinosa, C.; Romero, D.; Meseguer, J.; Cuesta, A.; Esteban Abad, María Ángeles; Ciencias SociosanitariasIn aquatic systems, mercury (Hg) is an environmental contaminant that causes acute and chronic damage to multiple organs. In fish, practically all of the organic Hg found is in the form of methylmercury (MeHg), which has been associated with animal and human health problems. This study evaluates the impact of waterborne-exposure to sublethal concentrations of MeHg (10 [mu]g L^sup -1^) in gilthead seabream (Sparus aurata). Hg was seen to accumulate in liver and muscle, and histopathological damage to skin and liver was detected. Fish exposed to MeHg showed a decreased biological antioxidant potential and increased levels of the reactive oxygen molecules compared with the values found in control fish (nonexposed). Increased liver antioxidant enzyme activities (superoxide dismutase and catalase) were detected in 2 day-exposed fish with respect to the values of control fish. However, fish exposed to MeHg for 10 days showed liver antioxidant enzyme levels similar to those of the control fish but had increased hepato-somatic index and histopathological alterations in liver and skin. Serum complement levels were higher in fish exposed to MeHg for 30 days than in control fish. Moreover, head-kidney leukocyte activities increased, although only phagocytosis and peroxidase activities showed a significant increase after 10 and 30 days, respectively. The data show that 30 days of exposure to waterborne MeHg provokes more significant changes in fish than a short-term exposure of 2 or 10 days.
- PublicationEmbargoMessage traffic and short-term illiquidity in high-speed markets(Elsevier, 2024-12-31) Abad, David; Massot, Magdalena; Nawn, Samarpan; Pascual, Roberto; Yagüe, José; AAAPrueba, Paco; AAAPrueba, Paco; Organización de Empresas y FinanzasWe examine which components of message traffic in a high-speed equity market, including orders from traders with varying technological capabilities, signal short-term illiquidity. Our findings show that only the unexpected component of high-frequency traders' (HFTs') net buying pressure — arising from both aggressive and non-aggressive orders — predicts increases in immediacy costs and price impacts. Updates to outstanding limit orders, driven by prior efficient pre returns, strengthen the signaling power of HFTs' order flow. Additionally, market-wide HFTs' net buying pressure improves the ability to forecast short-term illiquidity in individual stocks.