RESUMEN

Pesticide exposure is a risk factor for the development of several diseases, including breast cancer (BC). The enzyme UGT2B7 participate in detoxification of pesticides and the presence rs7438135 (G > A) variant in your gene increases its glucuronidation potential, contributing to oxidative stress metabolites neutralization. Here we investigated the impact of occupational pesticide exposure on the systemic oxidative stress generation from 228 women with BC depending on their UGT2B7 rs7438135 (G > A) status. q-PCR investigated the presence of the rs7438135 variant, and oxidative stress markers (lipid peroxidation levels, total antioxidant capacity-TRAP, and nitric oxide metabolites-NOx) were measured in plasma. Pesticide exposure induced significant augment in the systemic lipid peroxidation in the presence of the variant for several clinicopathological conditions, including tumors with high proliferation index (ki67) and with high aggressiveness. NOx was augmented in high ki67, positive progesterone receptors, high-grade and triple-negative/Luminal B tumors, and low-risk stratified patients. TRAP was depleted in young patients at menopause and those with triple-negative/Luminal B tumors, as well as those stratified as at low risk for death and recurrence. These findings showed that the presence of the variant was not able to protect from pesticide-induced oxidative stress generation in BC patients.

Asunto(s)

Neoplasias de la Mama , Glucuronosiltransferasa , Estrés Oxidativo , Plaguicidas , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Estrés Oxidativo/efectos de los fármacos , Plaguicidas/toxicidad , Persona de Mediana Edad , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Adulto , Pronóstico , Exposición Profesional/efectos adversos , Anciano , Alelos , Peroxidación de Lípido/efectos de los fármacos , Polimorfismo de Nucleótido Simple

RESUMEN

Nephrotoxicity is a common complication that limits the clinical utility of cisplatin. Ferroptosis is an iron-dependent necrotic cell death program that is mediated by phospholipid peroxidation. The molecular mechanisms that disrupt iron homeostasis and lead to ferroptosis are yet to be elucidated. In this study, we aimed to investigate the involvement of nuclear receptor coactivator 4 (NCOA4), a selective cargo receptor that mediates ferroptosis and autophagic degradation of ferritin in nephrotoxicity. Adult male Sprague-Dawley rats were randomly-assigned to four groups: control group, cisplatin (Cis)-treated group, deferiprone (DEF)-treated group, and Cis+DEF co-treated group. Serum, urine, and kidneys were isolated to perform biochemical, morphometric, and immunohistochemical analysis. Iron accumulation was found to predispose to ferroptotic damage of the renal tubular cells. Treatment with deferiprone highlights the role of ferroptosis in nephrotoxicity. Upregulation of NCOA4 in parallel with low ferritin level in renal tissue seems to participate in iron-induced ferroptosis. This study indicated that ferroptosis may participate in cisplatin-induced tubular cell death and nephrotoxicity through iron-mediated lipid peroxidation. Iron dyshomeostasis could be attributed to NCOA4-mediated ferritin degradation.

Asunto(s)

Cisplatino , Ferroptosis , Coactivadores de Receptor Nuclear , Ratas Sprague-Dawley , Transducción de Señal , Animales , Ferroptosis/efectos de los fármacos , Masculino , Cisplatino/toxicidad , Coactivadores de Receptor Nuclear/metabolismo , Transducción de Señal/efectos de los fármacos , Ratas , Deferiprona/farmacología , Sistema de Transporte de Aminoácidos y+/metabolismo , Antineoplásicos , Peroxidación de Lípido/efectos de los fármacos , Hierro/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Ferritinas/metabolismo , Enfermedades Renales/inducido químicamente , Enfermedades Renales/metabolismo , Inmunohistoquímica

RESUMEN

This study evaluated the effects of ora-pro-nobis (Pereskia aculeate) flour supplementation on the in vivo basal antioxidant system of Drosophila melanogaster, and its action on the neural modulation observed by the enzyme acetylcholinesterase (AChE). The flies will receive a standard diet with flour incorporated at 5, 10 and 20% for 7 days. There was no change in food consumption, body weight, protein thiol levels and negative geotaxis behavior. The flies showed a reduction in the basal production of reactive species at concentrations of 10 and 20%, while there was a reduction in lipid peroxidation and catalase activity at all concentrations, accompanied by an increase in the levels of non-protein thiols. Superoxide dismutase activity was reduced in the 5 and 20% groups, while the reduction of superoxide anion in the 10% group may have contributed to the increase in longevity also in the 10% group. Longevity increased in groups 5 and 10%. The open field test may be related to the reduction in AChE activity in the 5, 10 and 20% groups. In general, the data show that supplementation with ora-pro-nobis flour at the concentrations tested did not cause toxicity and modulated the cholinergic system, demonstrating a therapeutic potential.

Asunto(s)

Antioxidantes , Suplementos Dietéticos , Drosophila melanogaster , Longevidad , Animales , Drosophila melanogaster/efectos de los fármacos , Longevidad/efectos de los fármacos , Acetilcolinesterasa/metabolismo , Acetilcolinesterasa/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Superóxido Dismutasa/metabolismo , Femenino

RESUMEN

Maternal endotoxemia disturbs the intrauterine environment, impairs nephrogenesis, and increases the risk of hypertension and kidney disease in adulthood. Here, it was investigated whether maternal treatment with the water extract of Moringa oleifera seeds (WEMoS) or the water-soluble M. oleifera seed lectin (WSMoL) prevents the oxidative stress induced by lipopolysaccharide (LPS) in pregnant rats, and the renal injury and hypertension in the adult offspring. The administration of WEMoS or WSMoL prevented the stimulatory effects of LPS on lipid peroxidation in the maternal-placenta-fetuses environment. The impact of WEMoS was linked to decreased superoxide anions production in the placenta. The effects of WSMoL were parallel to the inhibition of superoxide anion production and NADPH oxidase activity. The WSMoL also prevented increased NADPH oxidase activity in the fetal kidney. The LPS offspring presented higher systolic blood pressure (SBP) and increased lipid peroxidation, reactive oxygen species (ROS), NADPH oxidase activity, and nitrate/nitrite in the kidney; the maternal treatment with WEMoS and WSMoL prevented these changes. In conclusion, the present study demonstrates that WEMoS and WSMoL have protective effects on maternal endotoxemia, which involve antioxidant and anti-inflammatory actions that prevent the programming of hypertension.

Asunto(s)

Hipertensión , Moringa oleifera , Estrés Oxidativo , Extractos Vegetales , Ratas Wistar , Semillas , Animales , Moringa oleifera/química , Estrés Oxidativo/efectos de los fármacos , Femenino , Semillas/química , Embarazo , Extractos Vegetales/farmacología , Hipertensión/prevención & control , Riñón/efectos de los fármacos , Ratas , Lipopolisacáridos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Especies Reactivas de Oxígeno/metabolismo , Lectinas/farmacología , Endotoxemia/prevención & control , Antioxidantes/farmacología

RESUMEN

This study evaluated the foliar antioxidant activity in nine Hevea brasiliensis genotypes from the ECC-1 (Élite Caquetá Colombia) selection and IAN 873 cultivar (control) in trees in the growth stage in two large-scale clonal trials in response to different climatic (semi-humid warm and humid warm sites) and seasonal (dry and rainy periods) conditions in the Colombian Amazon. The results indicated that Reactive Oxygen Species (ROS) production increased under conditions of lower water availability (dry period), leading to lipid peroxidation, high defense of photosynthetic pigments, and development of better osmotic adjustment capacity in the ECC 64, IAN 873, ECC 90, and ECC 35 genotypes due to high concentrations of carotenoids (0.40 mg g-1), reducing sugars (65.83 µg mg-1), and malondialdehyde (MDA) (2.44 nmol ml-1). In contrast, during the rainy period, a post-stress action was observed due to high contents of proline and total sugars (39.43 µg g-1 and 173.03 µg g-1, respectively). At the site level, with high Photosynthetically Active Radiation (PAR) values (1143 moles photons m-2 s-1), temperature (32.11°C), and lower precipitation (135 mm), higher antioxidant activity (chlorophylls a, b and total, carotenoids, and proline) was recorded at the humid warm site, demonstrating that the ECC 90, ECC 64, and ECC 66 genotypes are tolerant to water deficit compared to IAN 873. The ECC 64 genotype, independent of seasonal changes and site conditions, presented the highest contents in Chl a, total Chl, reducing sugars, total sugars, and MDA, showing a tendency to adapt to fluctuating conditions. This study showed that water fluctuations do not cause the same metabolic responses, these vary within the same species, depending on their developmental stage and the climatic and seasonal variations characteristic of the Colombian Amazon.

Asunto(s)

Antioxidantes , Genotipo , Hevea , Hojas de la Planta , Agua , Antioxidantes/metabolismo , Colombia , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Agua/metabolismo , Hevea/genética , Hevea/metabolismo , Fotosíntesis/genética , Fitomejoramiento/métodos , Carotenoides/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Malondialdehído/metabolismo , Peroxidación de Lípido , Estaciones del Año

RESUMEN

The addition of antioxidants to cryopreservation media reportedly improves sperm post-thaw quality and reproductive performance after artificial insemination. Therefore, the objectives of this study were to evaluate if the addition of L-carnitine and pyruvate to freezing media, or their addition to samples after thawing, improves the post-thaw quality of equine spermatozoa. Thus, in Experiment 1, stallion semen samples were cryopreserved in: (1) EDTA-glucose-based extender with 20% egg yolk and 5% dimethylformamide (EDTA control); (2) skim milk-based extender with 20% egg yolk and 5% dimethylformamide (milk control); (3) Extender 1 supplemented with 50 mM L-carnitine and 10 mM pyruvate (EDTA-carnitine-pyruvate); and (4) Extender 2 supplemented with 50 mM L-carnitine and 10 mM pyruvate (milk-carnitine-pyruvate). In Experiment 2, 50 mM L-carnitine and 10 mM pyruvate were added post-thaw to samples cryopreserved with extenders 1 and 2 (EDTA control and milk control). Sperm kinematic parameters, DNA fragmentation, membrane lipid peroxidation, acrosome status and viability were evaluated after thawing. No significant differences (p > 0.05) were observed for most of the kinematic parameters, DNA fragmentation, membrane lipid peroxidation, acrosome status and viability of spermatozoa, between the samples frozen in the presence or absence of L-carnitine and pyruvate, nor between the samples after the post-thaw addition of these components. A higher (p < 0.05) mean velocity and higher (p < 0.05) amplitude of lateral head displacement were observed in the samples frozen in the milk-based extender with the addition of L-carnitine and pyruvate after thawing. The addition of 50 mM L-carnitine and 10 mM pyruvate, either to the freezing extenders or after thawing, was not deleterious for sperm; however, it did not improve equine sperm motility, viability, acrosome and DNA integrity, nor decrease membrane lipid peroxidation after thawing.

Asunto(s)

Carnitina , Criopreservación , Crioprotectores , Fragmentación del ADN , Peroxidación de Lípido , Ácido Pirúvico , Preservación de Semen , Espermatozoides , Animales , Masculino , Caballos , Criopreservación/veterinaria , Criopreservación/métodos , Carnitina/farmacología , Carnitina/administración & dosificación , Preservación de Semen/veterinaria , Preservación de Semen/métodos , Espermatozoides/efectos de los fármacos , Espermatozoides/fisiología , Ácido Pirúvico/farmacología , Crioprotectores/farmacología , Peroxidación de Lípido/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Análisis de Semen/veterinaria , Acrosoma/efectos de los fármacos , Motilidad Espermática/efectos de los fármacos , Antioxidantes/farmacología

RESUMEN

During their development, amphibians undergo various physiological processes that may affect their susceptibility to environmental pollutants. Naturally occurring fluctuations caused by developmental events are often overlooked in ecotoxicological studies. Our aim is to investigate how biomarkers of oxidative stress are modulated at different stages of larval development in the Amazonian amphibian species, Physalaemus ephippifer. The premetamorphosis, prometamorphosis and metamorphic climax stages were used to analyze total antioxidant capacity (ACAP), glutathione S-transferase (GST) activity, lipid peroxidation (LPO) levels and the expression of genes nrf2, gst, gsr (glutathione reductase) and gclc (glycine-cysteine ligase, catalytic subunit). Although there was no difference in ACAP and the genes expression among the studied stages, individuals from the premetamorphosis and prometamorphosis showed higher GST activity than ones under the climax. LPO levels were highest in individuals from the metamorphic climax. The present study suggests that the oxidative status changes during ontogeny of P. ephippifer tadpoles, especially during the metamorphic climax, the most demanding developmental phase. Variations in the redox balance at different developmental stages may lead to a divergent response to pollution. Therefore, we recommend that studies using anuran larvae as biomonitors consider possible physiological differences during ontogeny in their respective analyses.

Asunto(s)

Anuros , Glutatión Transferasa , Larva , Peroxidación de Lípido , Oxidación-Reducción , Estrés Oxidativo , Animales , Anuros/metabolismo , Anuros/crecimiento & desarrollo , Larva/metabolismo , Larva/crecimiento & desarrollo , Glutatión Transferasa/metabolismo , Antioxidantes/metabolismo , Metamorfosis Biológica , Biomarcadores/metabolismo

RESUMEN

Chlorothalonil (CTL) is a pesticide widely used in Brazil, yet its mutagenic potential is not fully determined. Thus, we assessed the mutagenicity of CTL and its bioactivation metabolites using the somatic mutation and recombination test (SMART) in Drosophila melanogaster, by exposing individuals, with basal and high bioactivation capacities (standard and high bioactivation cross offspring, respectively), from third instar larval to early adult fly stages, to CTL-contaminated substrate (0.25, 1, 10 or 20 µM). This substrate served as food and as physical medium. Increased frequency of large single spots in standard cross flies' wings exposed to 0.25 µM indicates that, if CTL is genotoxic, it may affect Drosophila at early life stages. Since the total spot frequency did not change, CTL cannot be considered mutagenic in SMART. The same long-term exposure design was performed to test whether CTL induces oxidative imbalance in flies with basal (wild-type, WT) or high bioactivation (ORR strain) levels. CTL did not alter reactive oxygen species and antioxidant capacity against peroxyl radicals levels in adult flies. However, lipid peroxidation (LPO) levels were increased in WT male flies exposed to 1 µM CTL. SMART and LPO alterations were observed only in flies with basal bioactivation levels, pointing to direct CTL toxicity to DNA and lipids. Survival, emergence and locomotor behavior were not affected, indicating no bias due to lethality, developmental and behavioral impairment. We suggest that, if related to CTL exposure, DNA and lipid damages may be residual damage of earlier life stages of D. melanogaster.

Asunto(s)

Drosophila melanogaster , Pruebas de Mutagenicidad , Mutágenos , Nitrilos , Animales , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/genética , Nitrilos/toxicidad , Masculino , Pruebas de Mutagenicidad/métodos , Mutágenos/toxicidad , Femenino , Mutación/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Recombinación Genética/efectos de los fármacos , Plaguicidas/toxicidad , Estrés Oxidativo/efectos de los fármacos

RESUMEN

A great number of free radicals have a negative impact on the human body, and an increased interest in the identification of new natural molecules with antioxidant properties has emerged due to concerns about synthetic antioxidants. Here, the antioxidant effect of four exo-polysaccharides (EPS) extracts obtained from submerged cultivation of Nothophellinus andinopatagonicus and Pseudoinonotus crustosus (N and P, respectively) in two culture media (M1 and M2) at 2 concentrations (100 and 250 µg/ml) was studied; then, its relation with the chemical composition of the EPS was evaluated. To assess the antioxidant activities of the extracts, several in vitro assays were performed: DPPH and ABTS radical scavenging, ferric-reducing antioxidant power, chelating ability on ferrous ions, and inhibition of the lipid peroxidation. The concentrations tested here were much lower than those reported in previous works. Despite variations in chemical composition and monosaccharide profiles among the extracts, all demonstrated antioxidant activity, although the type of activity differed; only P-M1 exhibited a good antioxidant activity across all assays. This extract contained the highest proportion of phenolic compounds, and also displayed the highest radical scavenging activity. Although the utilization of polysaccharides as functional food ingredients remains limited, we propose P-M1 as a promising candidate for a nutraceutical product. Additionally, a formulation could be made with a combination of extracts to create an antioxidant-rich supplement. Additional research is needed to confirm our findings in a cellular environment and to elucidate the mechanisms that drive their antioxidant activities, ultimately facilitating their development and utilization as nutraceutical products.

Asunto(s)

Antioxidantes , Antioxidantes/farmacología , Antioxidantes/química , Polisacáridos Fúngicos/farmacología , Polisacáridos Fúngicos/química , Argentina , Polisacáridos/farmacología , Polisacáridos/química , Peroxidación de Lípido/efectos de los fármacos , Fenoles/farmacología , Fenoles/química , Hypocreales/química , Hypocreales/metabolismo , Benzotiazoles/metabolismo

RESUMEN

Mentha arvensis is an herbaceous plant commonly known as peppermint or Japanese mint. This study investigated the toxic potential and repellent efficacy of M. arvensis essential oil (MaEO) at varying concentrations (15.625-250 mg/mL) in Nauphoeta cinerea, along with its impact on biochemical parameters in N. cinerea. The potential of the major compounds as a new analgesic target was investigated using molecular docking. The essential oil was analyzed by gas Chromatography-mass spectrometry (GC-MS) and the toxic potential, repellent property, and changes in lipid peroxidation (LPO) levels were evaluated as markers of oxidative stress. GC-MS results revealed that the main components were oxygenated monoterpenes such as menthol (71.31%), mentone (13.34%) and isomentone (5.35%). MaEO significantly reduced lipid peroxidation (LPO), the levels of non-protein thiols and iron(II) at the concentration of 125 mg/mL in N. cinerea. Furthermore, the major components, L-(-)-Menthol and menthone demonstrated high gastrointestinal absorption and high affinity with the target protein, suggesting possible links that contribute to the analgesic effect of MaEO.

Asunto(s)

Antioxidantes , Peroxidación de Lípido , Mentha , Aceites Volátiles , Mentha/química , Antioxidantes/farmacología , Antioxidantes/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Peroxidación de Lípido/efectos de los fármacos , Animales , Simulación del Acoplamiento Molecular , Estrés Oxidativo/efectos de los fármacos , Cromatografía de Gases y Espectrometría de Masas , Repelentes de Insectos/farmacología , Repelentes de Insectos/química , Aceites de Plantas/farmacología , Aceites de Plantas/química

RESUMEN

Polycyclic aromatic hydrocarbons (PAHs), such as phenanthrene (PHE), are common pollutants found in coastal areas where shrimp farming is developed. Even though PAHs can have adverse effects on physiology, shrimp can detoxify and metabolize toxic compounds and neutralize the reactive oxygen species (ROS) produced during this process. This requires the activation of multiple antioxidant enzymes, including peroxiredoxin 6 (Prx6). Prx6 uses glutathione (GSH) to reduce phospholipid hydroperoxides, a function shared with GSH peroxidase 4 (GPx4). Prx6 has been scarcely studied in crustaceans exposed to pollutants. Herein, we report a novel Prx6 from the shrimp Penaeus vannamei that is abundantly expressed in gills and hepatopancreas. To elucidate the involvement of Prx6 in response to PAHs, we analyzed its expression in the hepatopancreas of shrimp sub-lethally exposed to PHE (3.3 µg/L) and acetone (control) for 24, 48, 72, and 96 h, along with GPx4 expression, GSH-dependent peroxidase activity, and lipid peroxidation (indicated by TBARS). We found that GPx4 expression is not affected by PHE, but Prx6 expression and peroxidase activity decreased during the trial. This might contribute to the rise of TBARS found at 48 h of exposure. However, maintaining GPx4 expression could aid to minimize lipid damage during longer periods of exposure to PHE.

Asunto(s)

Glutatión Peroxidasa , Peroxidación de Lípido , Penaeidae , Peroxiredoxina VI , Fenantrenos , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Animales , Fenantrenos/toxicidad , Peroxidación de Lípido/efectos de los fármacos , Penaeidae/metabolismo , Penaeidae/efectos de los fármacos , Penaeidae/genética , Penaeidae/enzimología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Peroxiredoxina VI/metabolismo , Peroxiredoxina VI/genética , Glutatión Peroxidasa/metabolismo , Glutatión Peroxidasa/genética , Contaminantes Químicos del Agua/toxicidad , Hepatopáncreas/metabolismo , Hepatopáncreas/efectos de los fármacos , Branquias/metabolismo , Branquias/efectos de los fármacos , Proteínas de Artrópodos/metabolismo , Proteínas de Artrópodos/genética

RESUMEN

This study explores the therapeutic benefits of tannic acid (TnA) in an experimental protocol of chronic hypermethioninemia in rats. Rats were categorized into four groups: Group I - control, Group II - TnA 30 mg/kg, Group III - methionine (Met) 0.2-0.4 g/kg + methionine sulfoxide (MS) 0.05-0.1 g/kg, Group IV - TnA/Met + MS. Saline was administered by subcutaneous pathway into groups I and II twice daily from postnatal day 6 (P6) to P28, whereas those in groups III and IV received Met + MS. From P28 to P35, groups II and IV received TnA orally. Animals from group III presented cognitive and memory impairment assessed through object recognition and Y-maze tests (p < 0.05). Elevated levels of reactive species, lipid peroxidation, and nitrites followed by a decline in sulfhydryl content, catalase activity, and superoxide dismutase activity were observed in animals treated with Met + MS (p < 0.05). However, TnA treatment reversed all these effects (p < 0.05). In group III, there was an increase in acetylcholinesterase activity and IL-6 levels, coupled with a reduction in Na+/K+-ATPase activity (p < 0.05). TnA was able to protect against these effects (p < 0.05). The gene expression of catalase, brain-derived neurotrophic factor, and nuclear factor erythroid 2-related factor 2 was decreased in the hippocampus and striatum from group III (p < 0.05). TnA reversed almost all of these alterations (p < 0.05). These findings suggest that TnA is a therapeutic target for patients with hypermethioninemia.

Asunto(s)

Errores Innatos del Metabolismo de los Aminoácidos , Taninos , Animales , Taninos/farmacología , Ratas , Errores Innatos del Metabolismo de los Aminoácidos/tratamiento farmacológico , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Masculino , Ratas Wistar , Peroxidación de Lípido/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Glicina N-Metiltransferasa/deficiencia , Polifenoles

RESUMEN

The influx of volcanic ash into seawater alters particle composition with implications for the cellular, physiological and anatomical response of suspension-feeding organisms. Adult females of Crepipatella peruviana were exposed to three diets consisting of a fixed concentration of 50,000 cells ml-1 of the microalga Isochrysis galbana plus different concentrations of ash particles (30, 90 and 150 mg L-1). The objective was to determine the cellular, physiological and anatomical responses. Mortality increased with ash concentrations, while feeding and respiration rates, tissue weight, and condition index decreased. The gills showed severe degradation of cilia and the presence of large mucous aggregates of cilia and ash. An increase in ash resulted in decreased lipid peroxidation and protein carbonyls, but increased total antioxidant capacity and phenols. Thus, volcanic ash particles may exert a high impact at both cellular and physiological levels for C. peruviana, where inhibition of gill function reduces the ability to acquire food.

Asunto(s)

Gastrópodos , Branquias , Gastrópodos/fisiología , Gastrópodos/efectos de los fármacos , Animales , Branquias/metabolismo , Branquias/efectos de los fármacos , Agua de Mar/química , Femenino , Erupciones Volcánicas , Peroxidación de Lípido/efectos de los fármacos , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad , Antioxidantes/metabolismo

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is a rising global burden, affecting one in four adults. Despite the increasing prevalence of NAFLD, the exact cellular and molecular mechanisms remain unclear, and effective therapeutic strategies are still limited. In vitro models of NAFLD are critical to understanding the pathogenesis and searching for effective therapies; thus, we evaluated the effects of free fatty acids (FFAs) on NAFLD hallmarks and their association with the modulation of Annexin A2 (ANXA2) and Keratin 17 (KRT17) in HepG2 cells. Our results show that oleic and palmitic acids can differentially induce intracellular lipid accumulation, cell death, and promote oxidative stress by increasing lipid peroxidation, protein carbonylation, and antioxidant defense depletion. Moreover, a markedly increased expression of inflammatory cytokines demonstrated the activation of inflammation pathways associated with lipotoxicity and oxidative stress. ANXA2 overexpression and KRT17 nuclear translocation were also observed, supporting the role of both molecules in the progression of liver disease. Taken together, these data provide insights into the interplay between ANXA2 and KRT17 in NAFLD, paving the way for understanding molecular mechanisms involved with the disease and developing new therapeutic strategies.

Asunto(s)

Anexina A2 , Ácidos Grasos no Esterificados , Enfermedad del Hígado Graso no Alcohólico , Estrés Oxidativo , Humanos , Anexina A2/metabolismo , Anexina A2/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Estrés Oxidativo/efectos de los fármacos , Células Hep G2 , Ácidos Grasos no Esterificados/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos

RESUMEN

Tributyltin (TBT) is an organotin compound that has several adverse health effects, including the development of obesity. Although obesity is strongly associated with adipose redox imbalance, there is a lack of information on whether TBT promotes a pro-oxidative environment in WAT. Thus, adult male Wistar rats were randomly exposed to either vehicle (ethanol 0.4%) or TBT (1000 ng/kg) for 30 days. Body and fat pad masses, visceral fat morphology, lipid peroxidation, protein carbonylation, redox status markers, and catalase activity were evaluated. TBT promoted increased adiposity and visceral fat, with hypertrophic adipocytes, but did not alter body mass and subcutaneous fat. ROS production and lipid peroxidation were elevated in TBT group, as well as catalase protein expression and activity, although protein oxidation and glutathione peroxidase protein expression remained unchanged. In conclusion, this is the first study to demonstrate that subacute TBT administration leads to visceral adipose redox imbalance, with increased oxidative stress. This enlights the understanding of the metabolic toxic outcomes of continuous exposure to TBT in mammals.

Asunto(s)

Adiposidad , Catalasa , Grasa Intraabdominal , Peroxidación de Lípido , Oxidación-Reducción , Estrés Oxidativo , Ratas Wistar , Compuestos de Trialquiltina , Animales , Masculino , Compuestos de Trialquiltina/toxicidad , Oxidación-Reducción/efectos de los fármacos , Grasa Intraabdominal/efectos de los fármacos , Grasa Intraabdominal/metabolismo , Adiposidad/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Catalasa/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Carbonilación Proteica/efectos de los fármacos , Glutatión Peroxidasa/metabolismo

RESUMEN

This study investigates the toxic effects of the insecticide spinetoram on the model organism Bombyx mori (Linnaeus) and explores the potential ameliorative properties of O-Vanillin. Sub-lethal concentrations of spinetoram were given to silkworm larvae via oral feed, resulting in reduced body weight, larval length, and impaired cocoon characteristics. A study of the enzymatic and non-enzymatic antioxidants revealed oxidative stress in the gut, fat body, and silk gland tissues, characterized by decreased antioxidants and increased lipid peroxidation. However, post-treatment with O-Vanillin effectively mitigated these toxic effects, preserving antioxidant capacities and preventing lipid peroxidation. Additionally, O-Vanillin prevented the loss of body weight and improved cocoon characteristics. At the histological level, spinetoram exposure caused mild histological damage in the gut, fat body, and silk gland. However, O-Vanillin post-treatment had ameliorative effects and mitigated the histological damages. To delve deeper into the mechanism of amelioration of O-Vanillin, in silico studies were used to study the interaction between an important xenobiotic metabolism protein of the Bombyx mori, i.e., Cytochrome p450, specifically CYP9A19, and O-Vanillin. We performed blind molecular docking followed by molecular dynamic simulation, and the results demonstrated stable binding interactions between O-Vanillin and CYP9A19, a cytochrome P450 protein in silkworm, belonging to the subfamily CYP9A, suggesting a potential role for O-vanillin in modulating xenobiotic metabolism.

Asunto(s)

Benzaldehídos , Bombyx , Insecticidas , Larva , Estrés Oxidativo , Animales , Bombyx/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Benzaldehídos/farmacología , Larva/efectos de los fármacos , Simulación del Acoplamiento Molecular , Antioxidantes , Peroxidación de Lípido/efectos de los fármacos

RESUMEN

There is a public health concern about the use of methylphenidate (MPH) since the higher prescription for young individuals and non-clinical purposes is addressed to the limited understanding of its neurochemical and psychiatric consequences. This study aimed to evaluate the impact of early and chronic MPH treatment on the striatum focusing on amino acid profile, glutamatergic excitotoxicity, redox status, neuroinflammation and glial cell responses. Male Wistar rats were treated with MPH (2.0 mg/kg) or saline solution from the 15th to the 44th postnatal day. Biochemical and histological analyses were conducted after the last administration. MPH altered the amino acid profile in the striatum, increasing glutamate and ornithine levels, while decreasing the levels of serine, phenylalanine, and branched-chain amino acids (leucine, valine, and isoleucine). Glutamate uptake and Na+,K+-ATPase activity were decreased in the striatum of MPH-treated rats as well as increased ATP levels, as indicator of glutamatergic excitotoxicity. Moreover, MPH caused lipid peroxidation and nitrative stress, increased TNF alpha expression, and induced high levels of astrocytes, and led to a decrease in BDNF levels. In summary, our results suggest that chronic early-age treatment with MPH induces parallel activation of damage-associated pathways in the striatum and increases its vulnerability during the juvenile period. In addition, data presented here contribute to shedding light on the mechanisms underlying MPH-induced striatal damage and its potential implications for neurodevelopmental disorders.

Asunto(s)

Aminoácidos , Astrocitos , Estimulantes del Sistema Nervioso Central , Cuerpo Estriado , Ácido Glutámico , Metilfenidato , Ratas Wistar , Animales , Masculino , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Metilfenidato/toxicidad , Metilfenidato/farmacología , Ácido Glutámico/metabolismo , Ratas , Estimulantes del Sistema Nervioso Central/toxicidad , Estimulantes del Sistema Nervioso Central/farmacología , Aminoácidos/metabolismo , Peroxidación de Lípido/efectos de los fármacos

RESUMEN

This study aimed to elucidate vincristine (VCR)-induced peripheral neuropathy in aged rats, a poorly understood neurotoxicity. Both young and old Wistar rats were administered VCR (0.1 mg/kg, intraperitoneally (i.p.)) and compared to age-matched controls (0.9% saline; 10 mg/mL, i.p.). Mechanical (MN) and thermal nociceptive (TN) responses were assessed on days 0, 6, 11, and 17. Locomotor response, cognitive ability, and anxious-like behavior were evaluated on days 14, 15, and 16. Results showed MN and TN responses in both young and old VCR-exposed rats. In old rats, VCR exacerbated MN (on days 6, 11, and 17) and TN (on days 6 and 17) responses. VCR also induced cognitive impairments and anxiety-like behavior. Histological analysis revealed Wallerian degeneration in the spinal cords of VCR-exposed rats accompanied by macrophage migration. Furthermore, VCR increased Ca2+-ATPase activity while inhibiting Na+, K+-ATPase activity in young and old rats. VCR altered the homeostasis of Mg2+-ATPase activity. Lipid peroxidation and nitrite and nitrate levels increased in young and old rats exposed to VCR. This study provides valuable insights into VCR's mechanistic pathways in aged rats, emphasizing the need for further research in this area.

Asunto(s)

Adenosina Trifosfatasas , Envejecimiento , Estrés Oxidativo , Enfermedades del Sistema Nervioso Periférico , Ratas Wistar , Vincristina , Degeneración Walleriana , Animales , Vincristina/farmacología , Vincristina/toxicidad , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/patología , Enfermedades del Sistema Nervioso Periférico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Degeneración Walleriana/inducido químicamente , Degeneración Walleriana/patología , Degeneración Walleriana/metabolismo , Masculino , Envejecimiento/efectos de los fármacos , Adenosina Trifosfatasas/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/patología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo

RESUMEN

Priming enables plants to respond more promptly, minimise damage, and survive subsequent stress events. Here, we aimed to assess the efficacy of priming and cross-priming in mitigating the stress caused by waterlogging and/or dehydration in soybeans (Glycine max ). Soybean plants were cultivated in a greenhouse in plastic pots in which soil moisture was maintained at pot capacity through irrigation. The first stress was applied in plants at the vegetative stage for 5days and involved either dehydration or waterlogging, depending on the treatment. Subsequently, the plants were irrigated or drained and maintained at pot capacity until the second stress. For the second stress, the conditions were repeated in plants at the reproductive stage. We then evaluated the levels of hydrogen peroxide (H2 O2 ), lipid peroxidation, total soluble sugars (TSS), amino acids, proline, and starch, and the activity of antioxidant, fermentative, and aminotransferase enzymes. Under waterlogging and dehydration, priming and cross-priming significantly increased the activity of antioxidant enzymes and the levels of TSS, amino acids, and proline while reducing H2 O2 concentration and lipid peroxidation. Under waterlogging, priming suppressed fermentative activity and increased carbohydrate content. This demonstrates that soybean plants activate their defence systems more promptly when subjected to priming.

Asunto(s)

Glycine max , Peróxido de Hidrógeno , Peroxidación de Lípido , Estrés Fisiológico , Agua , Glycine max/metabolismo , Peróxido de Hidrógeno/metabolismo , Agua/metabolismo , Deshidratación , Aminoácidos/metabolismo , Antioxidantes/metabolismo , Prolina/metabolismo

RESUMEN

This study investigated the impact of various Ge132 (Bis-carboxyethyl germanium sesquioxide) concentrations on frozen bovine semen. Ejaculates from three bulls were pooled and divided into six groups, each one with different Ge132 concentrations (0, 500, and 1000 µg/mL) and each group was incubated in different conditions (33°C for 30 min (D: D0, D500, and D1000), and the other was immediately cooled to 4°C (R: R0-control; R500 and R1000)). Thawed semen was evaluated for sperm characteristics by CASA and flow cytometer. Results showed better motility in the immediate cooling group without Ge132 compared with high Ge132 concentrations. Values for total motility dropped after 5 and 60 min in groups with high Ge132 levels and some control groups. Linearity increased with 1000 µg/mL Ge132, while straightness differed between moments in multiple groups. Membrane integrity was higher in a control group and certain Ge132 groups. Lower O2 - generation occurred without Ge132. After oxidative stress induction, lipid peroxidation intensity increased with arachidonic acid, but D1000 had lower peroxidation than R0. Overall, Ge132 appears to have provided protection against PLM when subjected to oxidative stress, since even at high concentrations it maintained sperm metabolism.

Asunto(s)

Antioxidantes , Criopreservación , Preservación de Semen , Motilidad Espermática , Espermatozoides , Animales , Masculino , Bovinos , Criopreservación/veterinaria , Criopreservación/métodos , Preservación de Semen/veterinaria , Preservación de Semen/métodos , Espermatozoides/efectos de los fármacos , Antioxidantes/farmacología , Motilidad Espermática/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Crioprotectores/farmacología , Peroxidación de Lípido/efectos de los fármacos , Germanio/farmacología , Semen/efectos de los fármacos , Análisis de Semen/veterinaria