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1.
Metab Brain Dis ; 39(4): 509-522, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38108941

RESUMO

Chlorpyrifos (CPF), considered one of the most potent organophosphates, causes a variety of human disorders including neurotoxicity. The current study was designed to evaluate the efficacy of hesperidin (HSP) in ameliorating CPF-induced neurotoxicity in rats. In the study, rats were treated with HSP (orally, 50 and 100 mg/kg) 30 min after giving CPF (orally, 6.75 mg/kg) for 28 consecutive days. Molecular, biochemical, and histological methods were used to investigate cholinergic enzymes, oxidative stress, inflammation, and apoptosis in the brain tissue. CPF intoxication resulted in inhibition of acetylcholinesterase (AChE) and butrylcholinesterase (BChE) enzymes, reduced antioxidant status [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH)], and elevation of malondialdehyde (MDA) levels and carbonic anhydrase (CA) activities. CPF increased histopathological changes and immunohistochemical expressions of 8-OHdG in brain tissue. CPF also increased levels of glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (NF-κB) while decreased levels of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α). Furthermore, CPF increased mRNA transcript levels of caspase-3, Bax, PARP-1, and VEGF, which are associated with apoptosis and endothelial damage in rat brain tissues. HSP treatment was found to protect brain tissue by reducing CPF-induced neurotoxicity. Overall, this study supports that HSP can be used to reduce CPF-induced neurotoxicity.


Assuntos
Apoptose , Clorpirifos , Hesperidina , Síndromes Neurotóxicas , Estresse Oxidativo , Animais , Estresse Oxidativo/efeitos dos fármacos , Hesperidina/farmacologia , Hesperidina/uso terapêutico , Clorpirifos/toxicidade , Apoptose/efeitos dos fármacos , Ratos , Masculino , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Ratos Wistar , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Inseticidas/toxicidade , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Inibidores da Colinesterase/farmacologia
2.
J Biochem Mol Toxicol ; 37(5): e23326, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36808657

RESUMO

Our experimental objective was to investigate the hepatotoxic effect of vincristine (VCR) administration in rats and determined whether combined therapy with Quercetin (Quer) ensured protection. Five groups with seven rats each were used for this purpose, and experimental groups were formulated as follows: Control group; Quer group; VCR group; VCR plus Quer 25 group; VCR plus Quer 50 group. The results showed that VCR significantly increased the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) enzymes. Besides, VCR caused considerable increases in the malondialdehyde (MDA) contents, along with significant decreases in reduced glutathione levels, superoxide dismutase, catalase, and glutathione peroxidase enzyme activities in the rat livers. Quer treatment in VCR toxicity markedly decreased the activity of ALT, AST, ALP enzymes, and MDA contents and enhanced the activities of antioxidant enzymes. The results also showed that VCR significantly increased the levels of NF-kB, STAT3, and the expression of caspase 3, Bax, and MAP LC3 and decreased the expression of Bcl2 and levels of Nrf2, HO-1, SIRT1, and PGC-1α. Compared to the VCR group, Quer treatment exhibited significantly lower levels of NF-kB, STAT3, and the expression of caspase 3, Bax, and MAP LC3, and higher levels of Nrf2, HO-1, SIRT1, and PGC-1α. In conclusion, our study demonstrated that Quer could alleviate the harmful effects of VCR via activation of NRf2/HO-1 and SIRT1/PGC-1α pathways, and via attenuation of oxidative stress, apoptosis, autophagy, and NF-kB/STAT3 pathways.


Assuntos
Antineoplásicos Fitogênicos , Doença Hepática Induzida por Substâncias e Drogas , Quercetina , Vincristina , Animais , Ratos , Vincristina/efeitos adversos , Masculino , Ratos Sprague-Dawley , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/veterinária , Quercetina/administração & dosagem , Fígado/química , Fígado/enzimologia , Fígado/patologia , Caspase 3/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Antineoplásicos Fitogênicos/efeitos adversos
3.
Alzheimers Dement ; 19(11): 4828-4840, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37023079

RESUMO

INTRODUCTION: Extracellular vesicles (EVs) may propagate and modulate Alzheimer's disease (AD) pathology. We aimed to comprehensively characterize the proteome of cerebrospinal fluid (CSF) EVs to identify proteins and pathways altered in AD. METHODS: CSF EVs were isolated by ultracentrifugation (Cohort 1) or Vn96 peptide (Cohort 2) from non-neurodegenerative controls (n = 15, 16) and AD patients (n = 22, 20, respectively). EVs were subjected to untargeted quantitative mass spectrometry-based proteomics. Results were validated by enzyme-linked immunosorbent assay (ELISA) in Cohorts 3 and 4, consisting of controls (n = 16, n = 43, (Cohort3, Cohort4)), and patients with AD (n = 24, n = 100). RESULTS: We found > 30 differentially expressed proteins in AD CSF EVs involved in immune-regulation. Increase of C1q levels in AD compared to non-demented controls was validated by ELISA (∼ 1.5 fold, p (Cohort 3) = 0.03, p (Cohort 4) = 0.005). DISCUSSION: EVs may be utilized as a potential biomarker and may play a so far unprecedented role in immune-regulation in AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Vesículas Extracelulares , Humanos , Doença de Alzheimer/patologia , Complemento C1q , Proteômica , Peptídeos beta-Amiloides/metabolismo , Fragmentos de Peptídeos/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Vesículas Extracelulares/metabolismo , Proteínas tau/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano
4.
Drug Chem Toxicol ; 45(3): 1308-1317, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-32957801

RESUMO

Morin is a flavonoid and broadly found in white berry and cranberry branch. Ifosfamide (IFOS) is known as an anticancer and cytotoxic drug especially on the liver. This study aimed to explore the potential protective effects of Morin against IFOS-induced liver toxicity in rats. The model group of rats received a single injection of IFOS (500 mg/kg; i.p.) at day 2, whereas the protective groups of rats were given two different doses of Morin (100 and 200 mg/kg; given by gavage) at days 1 and 2. All animals were then culled 24 h post-IFOS injection. We observed that IFOS caused liver injury, oxidative stress, inflammation, DNA damage, and apoptosis. However, Morin decreased the levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT) (p < 0.05). While Morin contributed to the recovery of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) levels, Morin decreased the levels of malondialdehyde (MDA) induced by IFOS in the liver (p < 0.05). Besides, the levels of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and P53 measured by ELISA test were reduced via Morin administration (p < 0.05). Lastly, the mRNA transcript levels of Bax, Apaf-1, Bcl-2, Bcl-xL, and inducible nitric oxide synthase (iNOS) determined by RT-PCR were down-regulated in the Morin groups (p < 0.05). These results indicate that Morin plays a protective role by reducing oxidative stress, inflammation, and apoptosis in the IFOS-induced liver injury in rats.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Ifosfamida , Animais , Antioxidantes/farmacologia , Apoptose , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Dano ao DNA , Flavonoides , Glutationa/metabolismo , Ifosfamida/metabolismo , Ifosfamida/toxicidade , Inflamação/patologia , Fígado , Estresse Oxidativo , Ratos , Superóxido Dismutase/metabolismo
5.
Int J Environ Health Res ; 32(10): 2149-2159, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34191661

RESUMO

The steady increase in the employment of silver nanoparticles (AgNPs) in consumer products entails the determination of the aquatic toxicity of AgNPs. Various AgNP characteristics including particle size, and shape, surface charge, and material have prominent effects on ecotoxicity. In the present study, we investigated the aquatic toxicity of chemically-synthesized AgNPs (Che-AgNPs) and green synthesis AgNPs (Gr-AgNPs) to Daphnia magna as a model organism. In each case, Che-AgNPs and Gr-AgNPs showed dose-dependent toxicity in the range of 5-50 ppb. It was also detected that the size and surface coverage material of AgNPs has a significant impact on the survival rate of D. magna. We also analyzed the expression of some genes related to detoxification and the reproductive system. These observations presented that in both NP types the significant alterations were detected in genes of the model organism in a dose-dependent manner.


Assuntos
Nanopartículas Metálicas , Poluentes Químicos da Água , Animais , Daphnia/metabolismo , Nanopartículas Metálicas/toxicidade , Tamanho da Partícula , Prata/metabolismo , Prata/toxicidade , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade
6.
Vet Med (Praha) ; 67(1): 1-12, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39169958

RESUMO

The aim of this study was to investigate the activity of apoptosis and autophagy in animals (cows, horses, donkeys, dogs and cats) naturally infected with rabies by using immunohistochemistry, immunofluorescence, and qPCR. The mRNA transcript levels of caspase-3, Bax, Bcl2 and LC3B were determined with qPCR. Caspase-3 and AIF immunopositivity were not observed in the immunohistochemical and immunofluorescence staining, whereas LC3B immunopositivity was determined intensively in the infected animals compared to the control groups. LC3B immunopositivity was detected in the cytoplasm of the Purkinje cells in the cerebellum of the cows, horses and donkeys, and also in the cytoplasm of the neurons in the cornu ammonis of the dogs and cats. While the expression levels of caspase-3 and Bax were downregulated, the Bcl2 expression was up-regulated in the infected animals compared to the uninfected animals. In addition, the LC3B levels were found to be significantly higher in the infected animals. To the best of our knowledge, this work represents the first report of neuronal death in the central nervous system by autophagy, rather than by caspase-dependent or AIF-containing caspase-independent apoptosis.

7.
Neurochem Res ; 46(2): 379-395, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33201400

RESUMO

Paclitaxel (PTX) is an antineoplastic agent commonly used in the treatment of solid tumors and is known to cause dose-limiting peripheral neurotoxicity. This study was performed to evaluate the protective effect of curcumin (CUR) against PTX-induced spinal cord and sciatic nerve injuries in rats. The rats were administered PTX (2 mg/kg, BW) intraperitoneally for the first 5 consecutive days followed by administration of CUR (100 and 200 mg/kg, BW daily in corn oil) orally for 10 days. Our results showed that CUR significantly reduced mRNA expression levels of NF-κB, TNF-α, IL-6, iNOS and GFAP whereas caused an increase in levels of Nrf2, HO-1 and NQO1 in the spinal cord and sciatic nerve of PTX-induced rats. In addition, CUR suppressed the activation of apoptotic and autophagic pathways by increasing Bcl-2 and Bcl-xL, and decreasing p53, caspase-3, Apaf-1, LC3A, LC3B and beclin-1 mRNA expression levels. The results showed that CUR also maintained the spinal cord and sciatic nerve histological architecture and integrity by both LFB staining and H&E staining. Immunohistochemical expressions of 8-OHdG, caspase-3 and LC3B in the PTX-induced spinal cord tissue were decreased after administration of CUR. Taken together, our findings demonstrated that CUR has protective effects on PTX-induced spinal cord and sciatic nerve injuries in rats.


Assuntos
Curcumina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Nervo Isquiático/efeitos dos fármacos , Neuropatia Ciática/tratamento farmacológico , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Paclitaxel , Ratos Sprague-Dawley , Nervo Isquiático/patologia , Neuropatia Ciática/induzido quimicamente , Neuropatia Ciática/patologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Traumatismos da Medula Espinal/induzido quimicamente , Traumatismos da Medula Espinal/patologia
8.
Fish Shellfish Immunol ; 115: 198-204, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33965523

RESUMO

Water temperature is one of the most important environmental factors affecting the growth and survival of fish. Increased water temperature became a global problem and it is estimated that there will be an increase in water temperature due to global climate change. The physiological mechanism for the effects of high water temperature on the fish brain is not fully known. In the present study, fish were exposed to different temperatures (10 °C/15 °C/20 °C/25°) and brain tissues were sampled 2 h-4h-6h-8h per hour respectively and then we investigated transcriptional changes of BDNF, cFOS, apoptotic genes (caspase 3, Bax, Bcl2), heat shock genes (Hsp70 and Hsp 90) ER-Stress genes (grp78, atf6, and ire1) and oxidative stress genes (CAT, SOD, and GPx) and also immunoflourescence changes of BDNF and cFOSin rainbow trout brain. The results indicated that high temperature stress lead to physiological changes in the fish brain by causing a decrease in mRNA expression levels of CAT, SOD, GPx and Bcl2 and by causing an increase in mRNA expression of BDNF, cFOS, apoptotic genes (caspase 3, Bax), heat shock genes (Hsp70 and Hsp 90) ER-Stress genes (grp78, atf6, and ire1). This study will provide important information to elucidate the physiological mechanisms related to the effects of high water temperature on the fish brain.


Assuntos
Encéfalo/fisiologia , Proteínas de Peixes/metabolismo , Temperatura Alta/efeitos adversos , Oncorhynchus mykiss/fisiologia , Água/química , Animais , Apoptose/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas de Choque Térmico/metabolismo , Estresse Oxidativo/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo
9.
Environ Toxicol ; 36(8): 1600-1617, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33908150

RESUMO

In this study, we investigated the effects of hesperidin (HSP) on oxidants/antioxidants status, inflammation, apoptotic, and autophagic activity in hepato-renal toxicity induced by chronic chlorpyrifos (CPF) exposure in rats. We used a total of 35 male albino rats in five groups of seven: control, HSP 100, CPF, CPF + HSP50, and CPF + HSP100. After rats were sacrificed, blood, liver, and kidney samples were collected. Serum levels of aspartate aminotransferases (ALT and AST), alkaline phosphatase (ALP), creatinine, and urea were tested. Then, contents of the superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), glutathione peroxidase (GPx), and glutathione (GSH) were measured to detect the level of oxidative stress in rat liver and renal tissues. We measured inflammatory and autophagy markers of chlorpyrifos induced oxidative stress in the liver and kidney tissues including TNF-α, iNOS, IL-1 ß, COX-2, NF-κB, MAPK14, and Beclin-1 using ELISA. Histopathological findings were also examined followed by immunohistochemical determination of 8-OHdG expression. Real-time PCR (RT-PCR) was used to examine Cas-3, Bax, Bcl-2, PARP-1, and VEGF, which are associated with apoptosis, autophagy, DNA, and endothelial damage, respectively. In addition, PARP-1 activity was supported by western blot and immunofluorescence, VEGF activity was supported by western blot methods. Treatment with HSP reduced the effect of CPF on ALT, AST, ALP, and total proteins, and increased its effect on tissue antioxidants. PARP/VEGF, apoptotic, pro-apoptotic, anti-apoptotic, and autophagic gene expressions were regulated, and Caspase-3 and Bax expressions were decreased; Bcl-2 expression increased in both the liver and kidney samples, and positivity of 8-OHdG and PARP-1 were reduced in the CPF plus HSP-treated group. Overall, the study demonstrates that HSP may reduce the effects of hepato-renal toxicity caused by CPF by regulating oxidative stress, inflammation, apoptosis, autophagy, and PARP/VEGF genes at biochemical, cellular, and molecular levels.


Assuntos
Clorpirifos , Hesperidina , Animais , Antioxidantes/metabolismo , Apoptose , Autofagia , Hesperidina/farmacologia , Inflamação/metabolismo , Fígado , Masculino , Estresse Oxidativo , Poli(ADP-Ribose) Polimerase-1 , Inibidores de Poli(ADP-Ribose) Polimerases/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Ratos , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Microb Pathog ; 147: 104426, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32768518

RESUMO

The immune response associated with mastitis caused by Mycoplasma bovis is a very complicated biological process in several type of cells, including immune cells, mammary epithelial cells, and endothelial cells. Thus, revealing of the microRNAs in the Mycoplasma bovis infected mammary gland tissues is particularly important for the immune response mechanism to Mycoplasma bovis. Firstly, 20 mammary gland tissue samples were collected from Holstein Friesian cattle that was located in Erzurum province at 2018 and screened for Mycoplasma bovis. Then, total RNA was isolated from Mycoplasma bovis infected tissues and high-throughput sequencing was performed. After bioinformatics analysis, GO and KEGG analysis of target genes of identified microRNAs were conducted. In this study, a total of 616 microRNAs were found. Our results revealed that 24 of the known microRNAs were expressed differently and 13 of the novel microRNAs were expressed differently in Mycoplasma bovis positive tissues. The target genes of these microRNAs were found to be associated with especially inflammation pathways, including B cell and T cell receptor signaling, Fc gamma R-mediated, phagocytosis/chemokine signaling, and MAPK signaling. In conclusion, this study demonstrated that identified miRNAs may be involved in the signaling pathways during mastitis caused by Mycoplasma bovis.


Assuntos
Infecções por Escherichia coli , Mastite Bovina , MicroRNAs , Infecções por Mycoplasma , Mycoplasma bovis , Animais , Bovinos , Células Endoteliais , Feminino , Glândulas Mamárias Animais , MicroRNAs/genética , Infecções por Mycoplasma/veterinária , Mycoplasma bovis/genética
11.
Mol Cell Probes ; 50: 101512, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31972225

RESUMO

Mycoplasma bovis (M. bovis) causes diseases such as arthritis, pneumonia, abortion, and mastitis, leading to great losses in the bovine dairy industries. RNA types such as messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) play significant roles in regulating the immune responses triggered by bacteria. The expression profiles of mRNA and lncRNA as they occur in bovine mammary gland tissues infected with M. bovis are still not well understood. To illuminate this issue, transcription analysis of mRNA and LncRNAs were conducted on the mammary gland tissues belonging to Holstein cattle infected and not infected with M. bovis. The analysis revealed 1310 differentially expressed mRNAs and 57 differentially expressed lncRNAs in the bovine mammary gland tissues infected and not infected with M. bovis. In addition, 392 novel lncRNAs were detected, 19 of which were differentially expressed. Gene ontology analysis reveals that differentially expressed mRNAs and lncRNAs play significant roles in such vital biological pathways as metabolic pathways, T-cell receptor signaling, TGF-beta signaling, pathways in cancer, PI3K-Akt signaling, NF-kappa B signaling, mTOR signaling, and apoptosis, including in the immune response to cancer. Based on our literature review, this study is the first genome-wide lncRNA research conducted on bovine mammary gland tissues infected with M. bovis. Our results provide bovine mammary gland lncRNA and mRNA resources to understand their roles in the regulation of the immune response against the agent M. bovis in bovine mammary gland tissues.


Assuntos
Genoma , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/microbiologia , Mycoplasma bovis/fisiologia , RNA Longo não Codificante/genética , Animais , Bovinos , Cromossomos de Mamíferos/genética , Análise por Conglomerados , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes
12.
Arch Virol ; 165(6): 1321-1331, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32253618

RESUMO

The aim of the study was to determine the expression profiles of GABAA, GABAB, and GAT1 using RT-PCR and the immunoreactivity of GAT1 via immunohistochemical and immunofluorescence assays in CDV-infected brain tissue of dogs. For this purpose, dogs with CDV and dogs without CDV were selected. The mRNA transcript levels of GABAA, GABAB, and GAT1 were significantly downregulated in brain tissue in the CDV-infected group as compared with that in non-CDV-infected brain tissue in the control group (p < 0.01, p < 0.001). In addition, the immunoreactivity of GAT1 in CDV-infected brain tissue was significantly lower than in the uninfected group (p < 0.05). We conclude that one of the main causes of myoclonus in CDV infections may be the blockage of postsynaptic inhibition in neurons or a lack of metabolism of GABA. In addition, a GABA neurotransmission imbalance could play a role in demyelination in CDV infections.


Assuntos
Encéfalo/metabolismo , Vírus da Cinomose Canina , Cinomose/metabolismo , Proteínas da Membrana Plasmática de Transporte de GABA/genética , Receptores de GABA-A/genética , Receptores de GABA-B/genética , Animais , Autofagia , Encéfalo/patologia , Encéfalo/virologia , Cinomose/patologia , Cães , Regulação para Baixo , Feminino , Masculino , Transcrição Gênica
13.
Virus Genes ; 56(2): 182-193, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31925640

RESUMO

African monkeys are resistant to HIV-1 infection due to intrinsic restriction mechanisms found in their cells. However, although they can be infected by monkey-adapted modified HIV-1 particles that are designed to overcome known restriction factors, virus numbers drop to undetectable levels in immunocompetent animals. These results indicate the possibility of the presence of yet unidentified factor(s) that restrict HIV-1 in old-world monkey (OWM) cells after integration of the viral genome into the host cell chromosome. In the light of these findings, we hypothesized that OWMs might have evolved resistance mechanism(s) against HIV-1 by switching specific gene(s) on in response to the synthesis of viral proteins in infected cells. In an attempt to mimic post-infection status, we expressed HIV-1 Tat gene in African green monkey cells and compared the whole proteome with normal cells and identified secretory leukocyte protease inhibitor (SLPI), a protein with known extracellular anti-HIV-1 activity, as an over-expressed protein in the presence of HIV-1 Tat protein by 2D-PAGE and mass spectrometry analysis. We also showed that overexpression of SLPI in the presence of HIV-1 Tat was specific to monkey cells. Our results also suggest that SLPI had a previously undiscovered intracellular anti-HIV activity in addition to its extracellular activity.


Assuntos
Infecções por HIV/genética , HIV-1/genética , Inibidor Secretado de Peptidases Leucocitárias/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Animais , Chlorocebus aethiops/genética , Regulação da Expressão Gênica no Desenvolvimento , Infecções por HIV/patologia , Infecções por HIV/virologia , HIV-1/patogenicidade , Humanos
14.
Mol Biol Rep ; 47(3): 2023-2034, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32030599

RESUMO

The purpose of the current study was to examine the neuroprotective effect of rutin against colistin-induced neurotoxicity in rats. Thirty-five male Sprague Dawley rats were randomly divided into 5 groups. The control group (orally received physiological saline), the rutin group (orally administered 100 mg/kg body weight), the colistin group (i.p. administered 15 mg/kg body weight), the Col + Rut 50 group (i.p. administered 15 mg/kg body weight of colistin, and orally received 50 mg/kg body weight of rutin), the Col + Rut 100 group (i.p. administered 15 mg/kg body weight of colistin, and orally received 100 mg/kg body weight of rutin). Administration of colistin increased levels of glial fibrillary acidic protein and brain-derived neurotrophic factor and acetylcholinesterase and butyrylcholinesterase activities while decreasing level of cyclic AMP response element binding protein and extracellular signal regulated kinases 1 and 2 (ERK1/2) expressions. Colistin increased oxidative impairments as evidenced by a decrease in level of nuclear factor erythroid 2-related factor 2 (Nrf-2), glutathione, superoxide dismutase, glutathione peroxidase and catalase activities, and increased malondialdehyde content. Colistin also increased the levels of the apoptotic and inflammatoric parameters such as cysteine aspartate specific protease-3 (caspase-3), p53, B-cell lymphoma-2 (Bcl-2), nuclear factor kappa B (NF-κB), Bcl-2 associated X protein (Bax), tumor necrosis factor-α (TNF-α) and neuronal nitric oxide synthase (nNOS). Rutin treatment restored the brain function by attenuating colistin-induced oxidative stress, apoptosis, inflammation, histopathological and immunohistochemical alteration suggesting that rutin supplementation mitigated colistin-induced neurotoxicity in male rats.


Assuntos
Apoptose/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/genética , Colistina/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Inflamação/etiologia , Inflamação/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Rutina/farmacologia , Animais , Biomarcadores , Encéfalo/metabolismo , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Colistina/efeitos adversos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Imuno-Histoquímica , Inflamação/patologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Ratos
15.
Int Immunopharmacol ; 126: 111264, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38016342

RESUMO

Acute Kidney Injury (AKI) is a major factor in sepsis-related mortality and may occur due to lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria that triggers a systemic acute inflammatory response. Quinacrine's (QC) renoprotective properties in sepsis and the underlying mechanism, however, are still not fully understood. This study was done to investigate the anti-inflammatory, antioxidative, and anti-apoptotic effects of QC, a phospholipase A2 (PLA2) inhibitor, against LPS-induced AKI. Rats were randomly divided into five groups: control group, QC30 group, LPS group, LPS+QC 10 group, and LPS+QC 30 group. The rats were administered intraperitoneally QC (10 and 30 mg/kg) for 3 days (once a day) prior to injection of LPS (3 mg/kg). Six hours after the LPS injection, the histopathological changes, oxidative stress, inflammation, and apoptosis in the collected kidney tissues were detected by hematoxylin and eosin staining, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and immunohistochemistry staining, respectively. QC pretreatment could successfully attenuate LPS-induced AKI, as evidenced by a decrease in tissue histopathological injury. Meanwhile, QC alleviated LPS-induced kidney oxidative stress; it reduced MDA levels and increased levels of SOD, CAT, GPX, and GSH. LPS-induced elevations in kidney TLR4, NF-κB, TNF-α, IL-1ß, IL-6, PLA2, caspase 3, and Bax contents were significantly attenuated in QC-treated groups. Our findings revealed a significant effect of QC: protecting against LPS-induced AKI through inhibition of PLA2 and decreasing inflammation, oxidative stress, and apoptosis. To treat LPS-induced AKI, QC may be an effective substance with an excellent protection profile.


Assuntos
Injúria Renal Aguda , Sepse , Ratos , Animais , NF-kappa B , Fator de Necrose Tumoral alfa/farmacologia , Lipopolissacarídeos/farmacologia , Receptor 4 Toll-Like , Quinacrina/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/patologia , Rim/patologia , Inflamação/patologia , Sepse/patologia
16.
Nat Med ; 30(6): 1771-1783, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38890531

RESUMO

Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases. Diagnostic groups comprised patients with TDP-43 proteinopathy ALS, 4R tauopathy progressive supranuclear palsy, behavior variant FTD (bvFTD) as a group with either tau or TDP-43 pathology, and healthy controls. EV tau ratios were low in progressive supranuclear palsy and high in bvFTD with tau pathology. EV TDP-43 levels were high in ALS and in bvFTD with TDP-43 pathology. Both markers discriminated between the diagnostic groups with area under the curve values >0.9, and between TDP-43 and tau pathology in bvFTD. Both markers strongly correlated with neurodegeneration, and clinical and neuropsychological markers of disease severity. Findings were replicated in an independent validation cohort of 292 patients including 34 genetically confirmed cases. Taken together, the combination of EV TDP-43 levels and EV 3R/4R tau ratios may aid the molecular diagnosis of FTD, FTD spectrum disorders and ALS, providing a potential biomarker to monitor disease progression and target engagement in clinical trials.


Assuntos
Esclerose Lateral Amiotrófica , Biomarcadores , Proteínas de Ligação a DNA , Vesículas Extracelulares , Demência Frontotemporal , Proteínas tau , Humanos , Esclerose Lateral Amiotrófica/sangue , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/genética , Proteínas tau/sangue , Proteínas tau/metabolismo , Vesículas Extracelulares/metabolismo , Demência Frontotemporal/sangue , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/genética , Demência Frontotemporal/patologia , Biomarcadores/sangue , Proteínas de Ligação a DNA/sangue , Proteínas de Ligação a DNA/genética , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Paralisia Supranuclear Progressiva/sangue , Paralisia Supranuclear Progressiva/diagnóstico , Isoformas de Proteínas/sangue
17.
Life Sci ; 332: 122096, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37716503

RESUMO

AIMS: Paclitaxel (Pax) is a chemotherapeutic drug from the taxane family that is used in the treatment of human cancer, including ovarian, breast, and non-small cell lung carcinoma. Chrysin (CR) has antioxidant, anti-inflammatory, anti-apoptotic, anti-diabetic, and anti-carcinogenic properties, as well as hepatoprotective and renoprotective activities. In the present study, we evaluated the protective effect of CR against Pax-induced hepatorenal toxicity on inflammation, apoptosis, antioxidant levels, oxidative DNA damage, and histopathology in rats. MATERIAL AND METHODS: Thirty-five male Sprague-Dawley rats were divided into five groups (n = 7): Group I (normal control), Group II (CR alone at a dose of 50 mg/kg), Group III (Pax at a dose of 2 mg/kg), Group IV (Pax+CR 25), and Group V (Pax+CR 50). The expressions of apoptotic (Bax and Bcl-2) and antioxidant genes (SOD1, CAT, GPx3, and GST) were evaluated using RT-PCR from paraffin sections. Caspase 3, KIM-1, NF-kB, COX-2, and 8-OHdG were also determined by immunohistochemical examination. KEY FINDINGS: The results revealed that Pax exposure caused hepatic and renal damage in rats, which was indicated by a significant elevation of caspase 3, Bax, KIM-1, NF-kB, COX-2, and 8-OHdG. However, there was a marked downregulation in the expressions of the Bcl-2, SOD1, CAT, GPx3, and GST genes. In contrast, rats given CR in combination showed better gene expression, histological structure, and immunohistochemical staining results. SIGNIFICANCE: Consequently, CR exhibited the ability to reduce oxidative DNA damage, exert anti-apoptotic and anti-inflammatory properties, and mitigate the toxic effects of Pax-induced hepatorenal toxicity.


Assuntos
Antioxidantes , Paclitaxel , Humanos , Ratos , Masculino , Animais , Antioxidantes/metabolismo , Caspase 3/metabolismo , Paclitaxel/farmacologia , NF-kappa B/metabolismo , Proteína X Associada a bcl-2/metabolismo , Ciclo-Oxigenase 2/metabolismo , Superóxido Dismutase-1/metabolismo , Ratos Sprague-Dawley , Estresse Oxidativo , Apoptose , Inflamação/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Anti-Inflamatórios/farmacologia
18.
Chemosphere ; 344: 140324, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37778644

RESUMO

Pesticides, such as cypermethrin (CYP) and chlorpyrifos (CPF), are widely used around the world and are known to cause toxicological effects in the brains of fish and other non-target organisms. Long non-coding RNAs (LncRNAs) are a new class of non-coding RNAs that are highly expressed in the brain and play crucial roles in brain function by regulating gene expression. Many studies have investigated the toxic effects of CYP and CPF on the brain. However, no study has been conducted on the relationship between LncRNAs and the toxicity caused by these chemicals. Therefore, this study aimed to determine changes in the lncRNA expression profile in the brains of fish exposed to CYP and CPF. Out of a total of 482 lncRNAs that were differentially expressed between control and CPF groups, 53 were found to be up-regulated, and 429 were down-regulated. Similarly, among the 200 lncRNAs differentially expressed between the control and CYP groups, 71 were up-regulated, and 129 were down-regulated. Additionally, 268 differentially expressed lncRNAs were identified between CYP and CPF groups, with 240 being up-regulated and the rest being down-regulated. In addition, LncRNAs expressed from fish brains exposed to CYP and CPF were found to regulate multiple signaling pathways, including MAPK, FoxO, PPAR, TGF-ß, and Wnt signaling pathways.


Assuntos
Clorpirifos , RNA Longo não Codificante , Animais , Clorpirifos/toxicidade , Peixe-Zebra/genética , RNA Longo não Codificante/genética , Encéfalo
19.
Vet Parasitol ; 314: 109855, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36528965

RESUMO

Bovine anaplasmosis is an arthropod-borne disease characterized by high fever, anaemia and sometimes jaundice. The role of oxidative stress in anaplasmosis has been investigated, but erythrocyte arginase (ARG) activity has not been studied. In this study, we aimed to investigate the changes in haematological parameters, erythrocyte ARG activity, plasma nitric oxide (NO) levels and oxidative stress parameters and explain the relationship between each other in cattle with anaplasmosis. The material of this study consisted of 14 cattle, aged 10-12 months with anaplasmosis (infected group) and 14 healthy cattle aged 10-12 months (control group). Our data revealed that leukocyte parameters and plasma NO levels and serum malondialdehyde (MDA), total oxidant status (TOS) and oxidative stress index (OSI) levels were higher while erythrocyte parameters, erythrocyte ARG activity and serum total antioxidant status (TAS) and glutathione (GSH) levels were lower in the infected group compared to the control group. There was a strong correlation between erythrocyte ARG activity and NO, MDA, TOS, OSI, TAS and GSH. ROC analysis and correlation results suggest that erythrocyte ARG activity is an effective oxidative stress marker. We concluded that severe oxidative stress occurs in anaplasmosis. As the severity of anaemia increases, erythrocyte ARG activity plummets while plasma NO level elevates. These two parameters may also be used as prognostic and oxidative stress markers. Although decreased erythrocyte ARG activity is a disadvantage in haemolytic diseases, this situation can be compensated by increased NO. Thus, homeostasis of these two parameters may contribute to the elimination of the infection.


Assuntos
Anaplasmose , Anemia , Doenças dos Bovinos , Bovinos , Animais , Óxido Nítrico , Arginase , Estresse Oxidativo , Antioxidantes/metabolismo , Eritrócitos , Oxidantes , Glutationa , Anemia/veterinária
20.
Chemosphere ; 298: 134330, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35304207

RESUMO

Circular RNAs (circRNAs) are a new class of non-endogenous coding RNA and an area with a lot of research interest and activity. Cypermethrin and chlorpyrifos have been shown to cause serious toxicological damage in the brain of fish and other non-target organisms. However, circRNAs associated with acute brain toxicity caused by cypermethrin and chlorpyrifos have not been studied yet. In this study, circRNAs were identified and characterized using RNA-seq in Zebrafish brains exposed to acute cypermethrin and chlorpyrifos toxicity. A total of 10,375 circRNAs were detected. It was determined that 6 circRNAs were up-regulated, 10 circRNAs were down-regulated in CYP brain samples compared to controls. In addition, it was found that 57 circRNAs are up-regulated and 3 circRNAs down-regulated in CPF brain samples compared to controls. Moreover, 62 circRNAs were down-regulated in the CYP samples, when CYP and CPF samples were compared. However, up-regulated circRNA could not be detected. It was revealed that the detected circRNAs specifically regulated the MAPK signaling pathway, endocytosis mechanism, apoptosis, and p53 signaling pathway. This study, which was conducted for the first time in terms of the subject of the study, could bring a different perspective, especially to pesticide toxicity studies.


Assuntos
Clorpirifos , Animais , Biomarcadores/metabolismo , Encéfalo/metabolismo , Clorpirifos/metabolismo , Clorpirifos/toxicidade , Piretrinas , RNA Circular/genética , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
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