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1.
Molecules ; 26(7)2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-33805024

RESUMEN

Depression and anxiety disorders are widespread diseases, and they belong to the leading causes of disability and greatest burdens on healthcare systems worldwide. It is expected that the numbers will dramatically rise during the COVID-19 pandemic. Established medications are not sufficient to adequately treat depression and are not available for everyone. Plants from traditional medicine may be promising alternatives to treat depressive symptoms. The model organism Chaenorhabditis elegans was used to assess the stress reducing effects of methanol/dichlormethane extracts from plants used in traditional medicine. After initial screening for antioxidant activity, nine extracts were selected for in vivo testing in oxidative stress, heat stress, and osmotic stress assays. Additionally, anti-aging properties were evaluated in lifespan assay. The extracts from Acanthopanax senticosus, Campsis grandiflora, Centella asiatica, Corydalis yanhusuo, Dan Zhi, Houttuynia cordata, Psoralea corylifolia, Valeriana officinalis, and Withaniasomnifera showed antioxidant activity of more than 15 Trolox equivalents per mg extract. The extracts significantly lowered ROS in mutants, increased resistance to heat stress and osmotic stress, and the extended lifespan of the nematodes. The plant extracts tested showed promising results in increasing stress resistance in the nematode model. Further analyses are needed, in order to unravel underlying mechanisms and transfer results to humans.


Asunto(s)
Antidepresivos/farmacología , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/fisiología , Extractos Vegetales/farmacología , Plantas Medicinales/química , Envejecimiento/efectos de los fármacos , Envejecimiento/fisiología , Animales , Antioxidantes/farmacología , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Técnicas de Inactivación de Genes , Respuesta al Choque Térmico/efectos de los fármacos , Longevidad/efectos de los fármacos , Longevidad/genética , Longevidad/fisiología , Mutación , Presión Osmótica/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismo
2.
Georgian Med News ; (311): 68-73, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33814394

RESUMEN

The aim - in the given research, the difficulties in interpreting the study results of oxidative homeostasis of oral fluid are analyzed. Changes in the total antioxidant activity of blood and saliva can be multidirectional - an increase or decrease in the oral fluid indicator and a reduction in the parameter of blood plasma can be recorded. To resolve the emerging difficulties, there was proposed a parallel assessment of the dynamics of changes in the total antioxidant activity of blood plasma and oral fluid in the patients of 4 groups with nosological forms of fundamentally different in the distribution and localization of the pathological process, which include: phlegmons of the maxillofacial region, partial absence of teeth, type 2 diabetes mellitus and the pelvic inflammatory diseases. As a result of the conducted studies, it was shown that a simultaneous decrease in the total antioxidant activity of blood plasma and oral fluid was attributable to the chronic long-term somatic diseases of a systemic character with a significant metabolic disorder, such as type 2 diabetes mellitus. A decrease in the total antioxidant activity of blood plasma and the unchanged oral fluid index was characteristic of somatic diseases of limited prevalence without affection of the maxillofacial region's tissues. In our case, such an example was a chronic inflammatory disease of the uterus with a combined course of bilateral salpingoophoritis. An increase in the oral fluid's total antioxidant activity on the background of a normal or even slightly reduced level of the antioxidant potential of blood plasma was characteristic of dental diseases. The latter situation was most likely for the dental profile diseases, in which damage to the oral tissues can provoke the leaching of cellular contents, including endogenous antioxidants or other components of regenerative activity in the oral fluid. Herein, changes in the antioxidant activity of blood plasma may reflect the prevalence of a pathological process at the systemic level or its limitation only to the dentoalveolar system's tissues and elements. As an example of such a situation, the patients with phlegmon of the maxillofacial region or patients with partial absence of teeth can be cited.


Asunto(s)
Antioxidantes , Diabetes Mellitus Tipo 2 , Femenino , Humanos , Oxidación-Reducción , Estrés Oxidativo , Saliva
3.
Anticancer Res ; 41(4): 1831-1840, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813388

RESUMEN

BACKGROUND/AIM: Peroxiredoxin V (Prx V) plays crucial roles in cellular apoptosis and proliferation in various cancer cells by regulating the cellular reactive oxygen species (ROS) levels. MATERIALS AND METHODS: Here, we examined the possible regulatory effects of Prx V on doxorubicin (DOX)-induced cellular apoptosis and its mechanisms in the human gastric adenocarcinoma cell line (AGS cells). RESULTS: Our findings suggest that Prx V knockdown may significantly increase the DOX-induced apoptosis by aggravating intracellular ROS accumulation. We also found that DOX-induced mitochondrial ROS levels and membrane permeability were significantly higher in short hairpin Prx V cells than in mock cells, and these phenomena were dramatically reversed by ROS scavenger treatment. Prx V knockdown also significantly upregulated the cleaved caspase 9, 3, and B-cell lymphoma 2 (Bcl2)-associated agonist of cell death/Bcl2 protein expression levels, suggesting that Prx V knockdown activates mitochondria-dependent apoptotic signaling pathways. CONCLUSION: Taken together, this study suggests that Prx V may be a strong molecular target for gastric cancer (GC) chemotherapy, and further elucidates the role of Prx V in oxidative stress-induced cell apoptosis.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antibióticos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Doxorrubicina/farmacología , Silenciador del Gen , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Peroxirredoxinas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/enzimología , Adenocarcinoma/genética , Adenocarcinoma/patología , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Mitocondrias/enzimología , Mitocondrias/patología , Peroxirredoxinas/genética , Transducción de Señal , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología
4.
Pestic Biochem Physiol ; 174: 104797, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33838701

RESUMEN

Tebuconazole (TEB) is a common triazole fungicide that has been widely used for the control of plant pathogenic fungi, suggesting that mammal exposure occurs regularly. Several studies demonstrated that TEB exposure has been linked to a variety of toxic effects, including neurotoxicity, immunotoxicity, reprotoxicity and carcinogenicity. However, there is a few available data regarding the molecular mechanism involved in TEB-induced toxicity. The current study was undertaken to investigate the toxic effects of TEB in HCT116 cells. Our results showed that TEB caused cytotoxicity by inhibiting cell viability as assessed by the MTT assay. Furthermore, we have demonstrated that TEB induced a significant increase in the reactive oxygen species (ROS) production leading to the induction of lipid peroxidation and DNA fragmentation and increased superoxide dismutase (SOD) and catalase (CAT) activities. Moreover, TEB exposure induced mitochondrial membrane potential loss and caspase-9/-3 activation. Treatment with general caspases inhibitor (Z-VAD-fmk) significantly prevented the TEB-induced cell death, indicating that TEB induced caspases-dependent cell death. These findings suggest the involvement of oxidative stress and apoptosis in TEB-induced toxicity in HCT116.


Asunto(s)
Daño del ADN , Triazoles , Animales , Apoptosis , Células HCT116 , Humanos , Estrés Oxidativo , Especies Reactivas de Oxígeno , Triazoles/toxicidad
5.
Pestic Biochem Physiol ; 174: 104810, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33838711

RESUMEN

The efficacies of three short synthetic antifungal peptides were tested for their inhibitory action on pathogenic fungi, Aspergillus flavus. The sequences of the short synthetic peptides are PPD1- FRLHF, 66-10-FRLKFH, 77-3- FRLKFHF, respectively. These test peptides inhibited fungal growth and showed a membranolytic activity. The fungal biomass and ergosterol levels were significantly low in peptides treated samples. Further, the fungal cell wall component chitin was also found to be lower in peptides treated samples. Scanning electron microscopic images also showed highly wrinkled fungal mycelia. Significant membrane permeabilisation as well as potassium ion leakage was also observed in fungal samples treated with peptides. To assess the membrane damage, the uptake of Sytox green dye was employed. At tested concentration, peptides induced fungal membrane damage as evidenced by the green fluorescence. Further, at tested concentration, these peptides induced an oxidative stress in A.flavus as evidenced by an increase in the ROS production, malondialdehyde levels, increase in the antioxidant enzymes - superoxide dismutase, catalase with concomitant decrease in the reduced glutathione content. Additionally, a growth dependent reduction in aflatoxin levels were also observed in peptides treated samples. Docking studies on the interaction of the peptides with a trans-membrane protein calcium ATPase of A. flavus showed that all the peptides were able to bind to the protein with high z rank score. The activity of the calcium ATPase was significantly decreased in peptides treated fungal samples, thereby validating the docking results. Among all the tested peptides, 77-3 peptide exhibited the maximal membrane damage property.


Asunto(s)
Aflatoxinas , Aspergillus flavus , Antifúngicos/farmacología , Estrés Oxidativo , Péptidos/farmacología
6.
Pestic Biochem Physiol ; 174: 104824, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33838717

RESUMEN

Acetamiprid is a new type of nicotinic insecticide that is widely used in pest control. Its environmental residues may cause silkworm cocooning disorder. In this study, silkworms that received continuous feeding of low concentration acetamiprid (0.15 mg/L) showed significantly decreased silk gland index and cocooning rate. Gene expression profiling of posterior silk glands (PSGs) revealed that the differentially expressed genes were significantly enriched in oxidative stress-related signal pathways with significant up-regulation. The contents of both H2O2 and MDA were increased, along with significantly elevated SOD and CAT activities, all of which reached maximal values at 48 h when H2O2 and MDA's contents were 10.46 and 7.98 nmol/mgprot, respectively, and SOD and CAT activities were 5.51 U/mgprot and 33.48 U/gprot, respectively. The transcription levels of antioxidant enzyme-related genes SOD, Mn-SOD, CuZn-SOD, CAT, TPX and GPX were all up-regulated, indicating that exposure to low concentration acetamiprid led to antioxidant response in silkworm PSG. The key genes in the FoxO/CncC/Keap1 signaling pathway that regulates antioxidant enzyme activity, FoxO, CncC, Keap1, NQO1, HO-1 and sMaf were all up-regulated during the whole process of treatment, with maximal values being reached at 72 h with 2.91, 1.46, 1.82, 2.52, 2.32 and 4.01 times of increases, respectively. These results demonstrate that exposure to low concentration acetamiprid causes oxidative stress in silkworm PSG, which may be the cause of cocooning disorder in silkworm. Our study provides a reference for the safety evaluation of environmental residues of acetamiprid on non-target insects.


Asunto(s)
Bombyx , Animales , Bombyx/genética , Bombyx/metabolismo , Crecimiento y Desarrollo , Peróxido de Hidrógeno , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch , Factor 2 Relacionado con NF-E2/metabolismo , Neonicotinoides , Estrés Oxidativo , Seda
7.
Pestic Biochem Physiol ; 174: 104825, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33838718

RESUMEN

Insecticide exposure typically leads to abnormally high levels of reactive oxygen species (ROS) and oxidative damage in insects. Superoxide dismutases (SODs) are potent antioxidant enzymes for ROS scavenging that are essential to protect insects against insecticide-induced oxidative injury. The small white butterfly, Pieris rapae, is an economically important lepidopteran pest of cruciferous crops, and the anthranilic diamide insecticide chlorantraniliprole is widely used to control this organism. However, whether chlorantraniliprole causes oxidative stress, and whether SODs are involved in ROS scavenging, remains unclear in P. rapae. In this study, an intracellular copper/zinc SOD (designated PrSOD1) gene was identified and characterised in P. rapae. The gene consists of four exons and three introns, and the PrSOD1 protein encoded by the gene has typical highly conserved features of CuZnSODs, including two signature motifs and seven Cu/Zn-interacting residues. Transcription of PrSOD1 was highest in the larval fat body and at the fifth-instar larval stage. Recombinant PrSOD1 protein expressed in Escherichia coli displayed antioxidant activity and high thermal and pH stability, confirming that PrSOD1 encodes a functional enzyme. Exposure to three sublethal doses of chlorantraniliprole for 6, 12 or 24 h resulted in significantly increased malondialdehyde concentration in P. rapae larvae, indicating insecticide-induced oxidative stress. Furthermore, both PrSOD1 transcription levels and CuZnSOD activity were quickly (6 and 12 h, respectively) upregulated in larvae subjected to chlorantraniliprole, strongly suggesting that PrSOD1 plays an important role in protecting against oxidative damage and possibly chlorantraniliprole tolerance in P. rapae.


Asunto(s)
Mariposas Diurnas , Animales , Cobre/toxicidad , Estrés Oxidativo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Zinc , ortoaminobenzoatos
8.
Nat Commun ; 12(1): 1728, 2021 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-33741927

RESUMEN

Microsomal glutathione S-transferase 2 (MGST2) produces leukotriene C4, key for intracrine signaling of endoplasmic reticulum (ER) stress, oxidative DNA damage and cell death. MGST2 trimer restricts catalysis to only one out of three active sites at a time, but the molecular basis is unknown. Here, we present crystal structures of human MGST2 combined with biochemical and computational evidence for a concerted mechanism, involving local unfolding coupled to global conformational changes that regulate catalysis. Furthermore, synchronized changes in the biconical central pore modulate the hydrophobicity and control solvent influx to optimize reaction conditions at the active site. These unique mechanistic insights pertain to other, structurally related, drug targets.


Asunto(s)
Glutatión Transferasa/química , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Sitios de Unión , Catálisis , Dominio Catalítico , Cristalografía por Rayos X , Retículo Endoplásmico/metabolismo , Humanos , Leucotrieno C4/metabolismo , Simulación de Dinámica Molecular , Mutagénesis Sitio-Dirigida , Estrés Oxidativo , Conformación Proteica
9.
Ecotoxicol Environ Saf ; 214: 112049, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33647852

RESUMEN

The disposal of untreated sanitary sewage in the soil has several consequences for human health and leads to environmental risks; thus, it is necessary investigating, monitoring and remediating the affected sites. The aims of the current study are to evaluate ecotoxicological effects on Eisenia andrei earthworms exposed to soil subjected to sources of sanitary sewage discharge and to investigate whether prevention values established by the Brazilian legislation for soil quality, associated with the incidence of chemical substances in it, are satisfactory enough to assure the necessary quality for different organisms. Earthworms' behavior, reproduction, acetylcholinesterase activity, catalase, superoxide dismutase and malondialdehyde levels were evaluated. The reproduction and behavior of earthworms exposed to sanitary sewage were adversely affected. Increased superoxide dismutase and catalase activity acted as antioxidant defense mechanism. Significantly increased lipid peroxidation levels and acetylcholinesterase activity inhibition have indicated lipid peroxidation in cell membrane and neurotransmission changes, respectively. Results have confirmed that sanitary sewage induced oxidative stress in earthworms. In addition, based on biochemical data analysis, the integrated biomarker response (IBR) has evidenced different toxicity levels in earthworms between the investigated points. Finally, results have indicated that effluents released into the soil, without proper treatment, lead to contaminant accumulation due to soil saturation and it can hinder different processes and biological development taking place in the soil. In addition, the current study has shown that physical-chemical analyses alone are not enough to assess soil quality, since it is also requires adopting an ecotoxicological approach. Brazilian legislation focused on soil quality must be revised and new guiding values must be proposed.


Asunto(s)
Oligoquetos/fisiología , Contaminantes del Suelo/análisis , Animales , Antioxidantes/metabolismo , Brasil , Catalasa/metabolismo , Ecotoxicología , Contaminación Ambiental/análisis , Humanos , Malondialdehído/metabolismo , Oligoquetos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Aguas del Alcantarillado , Suelo/química , Superóxido Dismutasa/metabolismo
10.
Environ Health Prev Med ; 26(1): 34, 2021 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-33706700

RESUMEN

BACKGROUND: Arsenic is a developmental neurotoxicant. It means that its neurotoxic effect could occur in offspring by maternal arsenic exposure. Our previous study showed that developmental arsenic exposure impaired social behavior and serotonergic system in C3H adult male mice. These effects might affect the next generation with no direct exposure to arsenic. This study aimed to detect the social behavior and related gene expression changes in F2 male mice born to gestationally arsenite-exposed F1 mice. METHODS: Pregnant C3H/HeN mice (F0) were given free access to tap water (control mice) or tap water containing 85 ppm sodium arsenite from days 8 to 18 of gestation. Arsenite was not given to F1 or F2 mice. The F2 mice were generated by mating among control F1 males and females, and arsenite-F1 males and females at the age of 10 weeks. At 41 weeks and 74 weeks of age respectively, F2 males were used for the assessment of social behavior by a three-chamber social behavior apparatus. Histological features of the prefrontal cortex were studied by ordinary light microscope. Social behavior-related gene expressions were determined in the prefrontal cortex by real time RT-PCR method. RESULTS: The arsenite-F2 male mice showed significantly poor sociability and social novelty preference in both 41-week-old group and 74-week-old group. There was no significant histological difference between the control mice and the arsenite-F2 mice. Regarding gene expression, serotonin receptor 5B (5-HT 5B) mRNA expression was significantly decreased (p < 0.05) in the arsenite-F2 male mice compared to the control F2 male mice in both groups. Brain-derived neurotrophic factor (BDNF) and dopamine receptor D1a (Drd1a) gene expressions were significantly decreased (p < 0.05) only in the arsenite-F2 male mice of the 74-week-old group. Heme oxygenase-1 (HO-1) gene expression was significantly increased (p < 0.001) in the arsenite-F2 male mice of both groups, but plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) and cyclooxygenase-2 (COX-2) gene expression were not significantly different. Interleukin-1ß (IL-1ß) mRNA expression was significantly increased only in 41-week-old arsenite-F2 mice. CONCLUSIONS: These findings suggest that maternal arsenic exposure affects social behavior in F2 male mice via serotonergic system in the prefrontal cortex. In this study, COX-2 were not increased although oxidative stress marker (HO-1) was increased significantly in arsnite-F2 male mice.


Asunto(s)
Arsénico/toxicidad , Arsenitos/toxicidad , Contaminantes Ambientales/toxicidad , Expresión Génica/efectos de los fármacos , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Conducta Social , Compuestos de Sodio/toxicidad , Animales , Conducta Animal/efectos de los fármacos , Femenino , Marcadores Genéticos , Masculino , Ratones , Ratones Endogámicos C3H , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Corteza Prefrontal/efectos de los fármacos , Embarazo , Efectos Tardíos de la Exposición Prenatal/genética , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/psicología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Serotonina/genética , Serotonina/metabolismo
11.
Ecotoxicol Environ Saf ; 214: 112058, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33714136

RESUMEN

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a nuclear transcription factor of great concern which is widely involved in physiological and pathological processes of the organism, but the role and regulatory mechanism of Nrf2 in kidney exposed to cadmium (Cd) remain largely unknown. Here we demonstrated that Cd exposure induced injury in primary rat proximal tubular (rPT) cells and NRK-52E cell line, which was accompanied by autophagic flux blockade and subsequent accumulation of p62. Cd-activated nucleus translocation of Nrf2 depended on p62, which promoted antioxidant genes transcription, but it failed to against Cd-induced cell injury and ultimately succumbed to Cd toxicity. CDDO Methyl Ester (CDDO-ME) or ML385 treatment aggravated or alleviated rPT cells injury induced by Cd respectively, indicating that Nrf2 nucleus translocation played a negative role during Cd-induced rPT cells injury. Phosphorylation of 5' AMP-activated protein kinase (AMPK) decreased together with enhanced Nrf2 nucleus translocation in rPT cells exposed to Cd. Dephosphorylation of AMPK induced by Cd were facilitated or restored by CDDO-ME or ML385 treatment, which confirmed AMPK is a downstream factor of Nrf2. Simultaneously, CDDO-ME further enhanced Phosphorylation of mTOR and AKT which increased during Cd exposure. While, Cd-induced phosphorylation of mTOR and AKT were reversed by ML385 treatment. These results illustrated that Cd mediated Nrf2 nucleus translocation depends on p62 accumulation which results from autophagic flux inhibition. The enhanced nucleus translocation of Nrf2 suppresses phosphorylation of AMPK to inactivate AKT/mTOR signaling, and results in rPT cells injury finally.


Asunto(s)
Cadmio/toxicidad , Contaminantes Ambientales/toxicidad , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Antioxidantes/metabolismo , Autofagia/efectos de los fármacos , Núcleo Celular/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Túbulos Renales Proximales/citología , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo
12.
Pestic Biochem Physiol ; 173: 104777, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33771256

RESUMEN

Ceratocystis fimbriata is the pathogen of black rot disease, which widely exists in sweet potato producing areas all over the world. The antifungal activity of volatile organic compounds (VOCs) released by Pseudomonas chlororaphis subsp. aureofaciens SPS-41 against C. fimbriata was reported in our previous study. In this study, we attempted to reveal the underlying antifungal mechanism of SPS-41 volatiles. Our results showed that the VOCs released by SPS-41 caused the morphological change of hyphae, destroyed the integrity of cell membrane, reduced the content of ergosterol, and induced massive accumulation of reactive oxygen species in C. fimbriata cells. Furthermore, SPS-41 fumigation decreased the mitochondrial membrane potential, acetyl-CoA and pyruvate content of C. fimbriata cells, as well as the mitochondrial dehydrogenases activity. In addition, the VOCs generated by SPS-41 reduced the intracellular ATP content and increased the extracellular ATP content of C. fimbriata. In summary, SPS-41 fumigation exerted its antifungal activity by inducing oxidative stress and mitochondrial dysfunction in C. fimbriata.


Asunto(s)
Ascomicetos , Compuestos Orgánicos Volátiles , Antifúngicos/farmacología , Mitocondrias , Estrés Oxidativo , Enfermedades de las Plantas , Pseudomonas , Compuestos Orgánicos Volátiles/farmacología
13.
Pestic Biochem Physiol ; 173: 104785, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33771263

RESUMEN

Luteolin (LUT) as a natural compound found in vegetables and fruits has various pharmacological effects. Fipronil (FPN), as a pesticide, has been considered for its effect on the antioxidant system and induction of oxidative stress. This study was designed to investigate the protective effects of LUT against the oxidative stress and mitochondrial toxicity induced by FPN on the rat brain. Several parameters such as mitochondrial reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, cytochrome c release, mitochondrial glutathione (GSH), lipid peroxidation (LPO) and Adenosine triphosphate (ATP) levels were assessed. Results indicated that the administration of LUT (25 µM) significantly improved oxidative stress and mitochondrial damages induced via FPN (6, 12 and 24 µM) in isolated mitochondria from the brain. These results show that LUT exerted protective effects against FPN-induced neurotoxicity in vitro through improving oxidative stress and mitochondrial damages.


Asunto(s)
Luteolina , Estrés Oxidativo , Animales , Encéfalo/metabolismo , Peroxidación de Lípido , Luteolina/farmacología , Potencial de la Membrana Mitocondrial , Mitocondrias/metabolismo , Pirazoles , Ratas , Especies Reactivas de Oxígeno/metabolismo
14.
Life Sci ; 273: 119303, 2021 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-33667518

RESUMEN

AIM: The current study aims to investigate the impact of paradoxical (REM) sleep deprivation and/or epileptic seizures on rat's cortical brain tissues. MAIN METHODS: Animals were divided into four groups; control, epileptic, REM sleep deprived and epileptic subjected to REM sleep deprivation. Electrocorticogram (ECoG) signals were recorded and quantitatively analyzed for each group. Concentrations of amino acid neurotransmitters; proinflammatory cytokines; and oxidative stress parameters; and acetylcholinesterase activity were determined in the cortex of the animals in different groups. KEY FINDINGS: Results showed significant variations in the spectral distribution of ECoG waves in the epilepsy model, 24- and 48-hours of REM sleep deprivation and their combined effects indicating a state of cortical hyperexcitability. Significant increases in NO and taurine and significant decrement in glutamine, GABA and glycine were determined. In REM sleep deprived rats significant elevation in glutamate, aspartate, glycine and taurine and a significant lowering in GABA were obtained. This was accompanied by significant reduction in AchE and IL-ß. In the cortical tissue of epileptic rats deprived from REM sleep significant increases in lipid peroxidation, TNF-α, IL-1ß, IL-6 and aspartate and a significant reduction in AchE were observed. SIGNIFICANCE: The present data indicate that REM sleep deprivation induces an increase in lipid peroxidation and storming in proinflammatory cytokines in the cortex of rat model of epilepsy during SRS. These changes are associated with a decreased seizure threshold as inferred from the increase in alpha and Beta waves and a decrease in Delta waves of ECoG.


Asunto(s)
Encéfalo/patología , Neurotransmisores/toxicidad , Estrés Oxidativo/efectos de los fármacos , Convulsiones/complicaciones , Privación de Sueño/complicaciones , Sueño REM/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Electrofisiología , Peroxidación de Lípido , Masculino , Ratas , Ratas Wistar
15.
Ecotoxicol Environ Saf ; 214: 112078, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33676053

RESUMEN

It is well known that the dairy cow production is very sensitive to environmental factors, including high temperature, high humidity and radiant heat sources. High temperature-induced heat stress is the main environmental factor that causes oxidative stress and apoptosis, which affects the development of mammary glands in dairy cows. Dihydromyricetin (DMY) is a nature flavonoid compound extracted from Ampelopsis grossedentata; it has been shown to have various pharmacological functions, such as anti-inflammation, antitumor and liver protection. The present study aims to evaluate the protective effect of DMY on heat stress-induced dairy cow mammary epithelial cells (DCMECs) apoptosis and explore the potential mechanisms. The results show that heat stress triggers heat shock response and reduces cell viability in DCMECs; pretreatment of DCMECs with DMY (25 µM) for 12 h significantly alleviates the negative effects of heat stress on cells. DMY can provide cytoprotective effects by suppressing heat stress-caused mitochondrial membrane depolarization and mitochondrial dysfunction, Bax and Caspase 3 activity, and modulation of oxidative enzymes, thereby preventing ROS production and apoptosis in DCMECs. Importantly, DMY treatment could attenuate heat stress-induced mitochondrial fragmentation through mediating the expression of mitochondrial fission and fusion-related genes, including Dynamin related protein 1 (Drp1), Mitochondrial fission 1 protein (Fis1), and Mitofusin1, 2 (Mfn1, 2). Above all, our findings demonstrate that DMY could protect DCMECs against heat stress-induced injury through preventing oxidative stress, the imbalance of mitochondrial fission and fusion, which provides useful evidence that DMY can be a promising therapeutic drug for protecting heat stress-induced mammary glands injury and mastitis.


Asunto(s)
Flavonoles/farmacología , Respuesta al Choque Térmico/efectos de los fármacos , Sustancias Protectoras/farmacología , Animales , Apoptosis/efectos de los fármacos , Bovinos , Supervivencia Celular/efectos de los fármacos , Dinaminas , Células Epiteliales/efectos de los fármacos , Femenino , Mitocondrias/efectos de los fármacos , Dinámicas Mitocondriales/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos
16.
Ecotoxicol Environ Saf ; 214: 112081, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33677383

RESUMEN

Perfluorooctanoic acid (PFOA), a persistent environmental contaminant, resists environmental degradation and bioaccumulates in food chains. Lots of literatures have proved that PFOA exposure could disrupt detoxifying function in a variety of organisms, however, it still remained poorly known about this in mollusk. Here, we examined physiological, transcriptomic, and metabolomic responses to PFOA in Mytilus edulis, a model organism frequently used in studies of aquatic pollution. We aimed to characterize PFOA-induced stress responses and detoxification mechanisms. PFOA exposure significantly altered antioxidant enzyme activity levels and the abundances of lipid peroxidation products. In addition, transcriptomic analysis indicated that several genes associated with oxidative stress and detoxication were differentially expressed after PFOA exposure. In combination, transcriptomic and metabolomic analyses showed that PFOA exposure disturbed several metabolic processes in M. edulis, including the lipid metabolism, amino acid metabolism, and carbohydrate metabolism etc. Molecular examination and enzymes assay of PFOA-exposed M. edulis after a 7-day depuration period still did not recover to control levels. The Pathway enrichment analysis proved that several pathways related to detoxification, such as c-Jun N-terminal kinase (JNK) and p38-dependent mitogen-activated protein kinase (MAPK) pathway, Peroxisome proliferator-activated receptor γ (PPARγ) pathway etc, were obviously affected. The present work verifies firstly PFOA disruption to molluscan detoxification and identifies the key pathways to understand the molecular mechanisms thereof. This study provides new insights into the detoxication disruption invoked in response to PFOA exposure in M. edulis.


Asunto(s)
Caprilatos/toxicidad , Fluorocarburos/toxicidad , Mytilus edulis/fisiología , Animales , Antioxidantes/metabolismo , Metabolismo de los Lípidos , Metabolómica , Mytilus edulis/metabolismo , Estrés Oxidativo , PPAR gamma/metabolismo , Transcriptoma
17.
Ecotoxicol Environ Saf ; 214: 112091, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33706141

RESUMEN

The occurrence of cadmium (Cd) in feed is a major problem in animal health and production. Studies have confirmed that Cd depresses egg production of laying hens, which is closely related to follicular atresia. This study aimed to assess the toxic impacts of Cd on the ovarian tissue, and to examine the mechanism of Cd-induced granulosa cell proliferation and apoptosis. Results from the nitric oxide (NO) and malondialdehyde (MDA) content, total superoxide dismutase (T-SOD), glutathione peroxide (GSH-Px), total nitric oxide synthase (T-NOS) and adenosine triphosphatase (ATPase) activities, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, and hematoxylin-eosin (H & E) staining indicated that excess Cd induced oxidative stress, granulosa cell apoptosis and follicular atresia in the layer ovary. Low-dose Cd exposure (1 µM) induced the granulosa cell proliferation, upregulated the mRNA levels of RSK1 and RHEB, activated FoxO3a, AKT, ERK1/2, mTOR and p70S6K1 phosphorylation, and promoted cell cycle progression from phase G1 to S. However, high-dose Cd exposure (15 µM) induced reactive oxygen species (ROS) generation and cell apoptosis, upregulated the mRNA levels of the inflammatory factors, ASK1, JNK, p38 and TAK1, downregulated the expressions of RSK1 and RHEB genes, and inhibited the phosphorylation of ERK1/2, mTOR and p70S6K1 proteins, and the cell cycle progression. Rapamycin pre-treatment completely blocked the phosphorylation of mTOR and p70S6K1 proteins, and the cell cycle progression induced by 1 µM Cd, and accelerated 15 µM Cd-induced cell apoptosis and cell cycle arrest. The microRNA sequencing result showed that 15 µM Cd induced differential expression of microRNA genes, which may regulate AKT, ERK1/2 and mTOR signaling and cell cycle progression by regulating the activity of G proteins and cell cycle-related proteins. Conclusively, these results indicated that Cd can cause the ovarian damage and follicular atresia, and regulate cell cycle, cell proliferation or apoptosis of granulosa cells through MAPK, AKT/FoxO3a and mTOR pathways in laying hens.


Asunto(s)
Cadmio/toxicidad , Células de la Granulosa/efectos de los fármacos , Animales , Apoptosis , Ciclo Celular , Puntos de Control del Ciclo Celular , División Celular , Proliferación Celular , Pollos/metabolismo , Femenino , Atresia Folicular , Células de la Granulosa/metabolismo , Etiquetado Corte-Fin in Situ , Estrés Oxidativo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo
18.
Molecules ; 26(5)2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33652584

RESUMEN

The purpose of the research was to examine the protective effect of essential oil from Thymus serrulatus Hochst. ex Benth. (TSA oil) against cadmium (Cd)-induced renal toxicity. The experimental protocol was designed using 30 healthy adult Wistar albino rats allocated into five groups containing six animals in each group. Group 1 was treated as normal control and groups 2, 3, 4, and 5 were treated with cadmium chloride (CdCl2, 3 mg/kg, IP) for 7 days. Group 3 was also treated with silymarin (100 mg/kg, PO) as a standard group, while groups 4 and 5 were administered with TSA oil at doses of 100 and 200 mg/kg PO, respectively. The nephrotoxicity was measured with various parameters such as kidney function markers, oxidative stress markers (glutathione (GSH) and malondialdehyde (MDA)), and messenger ribonucleic acid (mRNA) expression levels of inflammatory factors. The histological studies were also evaluated in the experimental protocol. The CdCl2-treated groups showed a significant increase in the levels of serum kidney function markers along with MDA levels in kidney homogenate. However, renal GSH level was found to be reduced significantly. It was found that CdCl2 significantly upregulated the nuclear factor levels of kappaB (NF-κB p65), inducible nitric oxide synthase (iNOS), and small mothers against decapentaplegic (Smad2) as compared to the normal control group. On the other hand, TSA oil significantly improved the increased levels of serum kidney function markers, non-enzymatic antioxidants, and lipid peroxidation. In addition, TSA oil significantly downregulated the increased expression of NF-κB p65, iNOS, and Smad2 in Cd-intoxicated rats. Moreover, the histological changes in the tissue samples of the kidney of Cd-treated groups were significantly ameliorated in the silymarin- and TSA-oil-treated groups. The present study reveals that TSA oil ameliorates Cd-induced renal injury, and it is also proposed that the observed nephroprotective effect could be due to the antioxidant potential of TSA oil and healing due to its anti-inflammatory action.


Asunto(s)
Enfermedades Renales/tratamiento farmacológico , Aceites Volátiles/química , Estrés Oxidativo/efectos de los fármacos , Thymus (Planta)/química , Animales , Antioxidantes/química , Antioxidantes/farmacología , Cadmio/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Riñón/efectos de los fármacos , Riñón/patología , Enfermedades Renales/inducido químicamente , FN-kappa B/genética , Óxido Nítrico Sintasa de Tipo II/genética , Aceites Volátiles/farmacología , Ratas , Proteína Smad2/genética
19.
Chemistry ; 27(19): 6015-6027, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33666306

RESUMEN

Many (poly-)phenolic natural products, for example, curcumin and taxifolin, have been studied for their activity against specific hallmarks of neurodegeneration, such as amyloid-ß 42 (Aß42) aggregation and neuroinflammation. Due to their drawbacks, arising from poor pharmacokinetics, rapid metabolism, and even instability in aqueous medium, the biological activity of azobenzene compounds carrying a pharmacophoric catechol group, which have been designed as bioisoteres of curcumin has been examined. Molecular simulations reveal the ability of these compounds to form a hydrophobic cluster with Aß42, which adopts different folds, affecting the propensity to populate fibril-like conformations. Furthermore, the curcumin bioisosteres exceeded the parent compound in activity against Aß42 aggregation inhibition, glutamate-induced intracellular oxidative stress in HT22 cells, and neuroinflammation in microglial BV-2 cells. The most active compound prevented apoptosis of HT22 cells at a concentration of 2.5 µm (83 % cell survival), whereas curcumin only showed very low protection at 10 µm (21 % cell survival).


Asunto(s)
Amiloidosis , Curcumina , Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Curcumina/farmacología , Humanos , Estrés Oxidativo
20.
Mutat Res ; 863-864: 503313, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33678245

RESUMEN

Biological dosimetry of ionizing radiation (IR) exposure relies on validated cytogenetic tests measuring the frequencies of micronuclei (MN) and dicentric chromosomes (DC). IR also causes oxidative damage of biomolecules, including DNA. We evaluated IR-induced genotoxic and oxidative damage in a carefully defined cohort of healthy donors, reducing confounding factors as much as possible. Frequencies of MN and DC (peripheral blood lymphocyte cultures) and oxidative stress parameters (plasma) were quantified. We observed dose dependence of both cytogenetic and biochemical endpoints, independent of age, sex, and smoking habits. Oxidative stress parameters, especially oxidative stress index, malondialdehyde, advanced oxidation protein products, and catalase, may be used confidently to assess IR-induced damage, if cytogenetic results are unavailable.


Asunto(s)
Aberraciones Cromosómicas/efectos de la radiación , Linfocitos/metabolismo , Estrés Oxidativo/efectos de la radiación , Plasma/metabolismo , Traumatismos por Radiación/metabolismo , Radiación Ionizante , Adulto , Femenino , Humanos , Linfocitos/patología , Masculino , Persona de Mediana Edad , Traumatismos por Radiación/patología
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