RESUMEN
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.
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Esclerosis Amiotrófica Lateral , Biomarcadores , Proteínas de Unión al ADN , Vesículas Extracelulares , Demencia Frontotemporal , Proteínas tau , Humanos , Esclerosis Amiotrófica Lateral/sangre , Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/patología , Esclerosis Amiotrófica Lateral/genética , Proteínas tau/sangre , Proteínas tau/metabolismo , Vesículas Extracelulares/metabolismo , Demencia Frontotemporal/sangre , Demencia Frontotemporal/diagnóstico , Demencia Frontotemporal/genética , Demencia Frontotemporal/patología , Biomarcadores/sangre , Proteínas de Unión al ADN/sangre , Proteínas de Unión al ADN/genética , Femenino , Masculino , Anciano , Persona de Mediana Edad , Parálisis Supranuclear Progresiva/sangre , Parálisis Supranuclear Progresiva/diagnóstico , Isoformas de Proteínas/sangreAsunto(s)
Piretrinas , Rutina , Masculino , Ratas , Animales , Rutina/farmacología , Testículo , Piretrinas/toxicidad , Nitrilos/metabolismo , Estrés Oxidativo , Antioxidantes/farmacologíaRESUMEN
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.
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Lesión Renal Aguda , Sepsis , Ratas , Animales , FN-kappa B , Factor de Necrosis Tumoral alfa/farmacología , Lipopolisacáridos/farmacología , Receptor Toll-Like 4 , Quinacrina/efectos adversos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/patología , Riñón/patología , Inflamación/patología , Sepsis/patologíaRESUMEN
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.
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Apoptosis , Cloropirifos , Hesperidina , Síndromes de Neurotoxicidad , Estrés Oxidativo , Animales , Estrés Oxidativo/efectos de los fármacos , Hesperidina/farmacología , Hesperidina/uso terapéutico , Cloropirifos/toxicidad , Apoptosis/efectos de los fármacos , Ratas , Masculino , Síndromes de Neurotoxicidad/tratamiento farmacológico , Síndromes de Neurotoxicidad/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Ratas Wistar , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/inducido químicamente , Insecticidas/toxicidad , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Inhibidores de la Colinesterasa/farmacologíaRESUMEN
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.
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Cloropirifos , ARN Largo no Codificante , Animales , Cloropirifos/toxicidad , Pez Cebra/genética , ARN Largo no Codificante/genética , EncéfaloRESUMEN
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.
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Antioxidantes , Paclitaxel , Humanos , Ratas , Masculino , Animales , Antioxidantes/metabolismo , Caspasa 3/metabolismo , Paclitaxel/farmacología , FN-kappa B/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Ciclooxigenasa 2/metabolismo , Superóxido Dismutasa-1/metabolismo , Ratas Sprague-Dawley , Estrés Oxidativo , Apoptosis , Inflamación/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Antiinflamatorios/farmacologíaRESUMEN
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 (â¼ 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.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Vesículas Extracelulares , Humanos , Enfermedad de Alzheimer/patología , Complemento C1q , Proteómica , Péptidos beta-Amiloides/metabolismo , Fragmentos de Péptidos/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Vesículas Extracelulares/metabolismo , Proteínas tau/líquido cefalorraquídeo , Disfunción Cognitiva/líquido cefalorraquídeoRESUMEN
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.
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Antineoplásicos Fitogénicos , Enfermedad Hepática Inducida por Sustancias y Drogas , Quercetina , Vincristina , Animales , Ratas , Vincristina/efectos adversos , Masculino , Ratas Sprague-Dawley , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/veterinaria , Quercetina/administración & dosificación , Hígado/química , Hígado/enzimología , Hígado/patología , Caspasa 3/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Antineoplásicos Fitogénicos/efectos adversosRESUMEN
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.
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Anaplasmosis , Anemia , Enfermedades de los Bovinos , Bovinos , Animales , Óxido Nítrico , Arginasa , Estrés Oxidativo , Antioxidantes/metabolismo , Eritrocitos , Oxidantes , Glutatión , Anemia/veterinariaRESUMEN
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.
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Cloropirifos , Animales , Biomarcadores/metabolismo , Encéfalo/metabolismo , Cloropirifos/metabolismo , Cloropirifos/toxicidad , Piretrinas , ARN Circular/genética , Pez Cebra/genética , Pez Cebra/metabolismoRESUMEN
Bortezomib (BTZ), a proteasome inhibitor, causes dose-limiting peripheral neuropathy in humans. Berberine (BBR), which has various biological and pharmacological properties, is known to have neuroprotective properties. The possible protective effects of BBR on peripheral neuropathy caused by BTZ were investigated in this study. For this purpose, BTZ was intraperitoneally given to Sprague dawley rats on the 1 st, 3rd, 5th, and 7th days with a cumulative dose of 0.8 mg/kg. Moreover, animals were orally administered 50 or 100 mg/kg BBR daily from day 1 to day 10. As a result of the analyzes performed on the sciatic nerve and spinal cord, it was observed that MDA levels and NRF-2, HO-1, NQO1, GCLC and GCLM mRNA transcript levels increased due to oxidative stress caused by BTZ, and the levels of these markers decreased after BBR administration. Also, it was determined that SOD, CAT, GPx and GSH levels increased after BBR treatment. It was observed that BTZ caused inflammation by triggering NF-κB, TNF-α, IL-1ß and IL-6 cytokines, on the other hand, with BBR treatment, these cytokines were suppressed and inflammation was alleviated. In addition, it was determined that the expressions of RAGE, STAT3, NLRP3 and TLR4, which have important roles in inflammation, increased with BTZ administration, but BBR suppressed the expressions of these genes. It was determined that the expressions of SIRT1, which plays an important role in neuropathic pain, and CREB-LI neurons, which has an active role in neurite outgrowth and survival, decreased with BTZ administration. It was observed that GFAP levels increased with BTZ administration and decreased with BBR administration. Given all the findings, it was concluded that BBR exhibits protective qualities in the sciatic nerve and spinal cord induced by BTZ.
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Berberina , Animales , Berberina/farmacología , Berberina/uso terapéutico , Bortezomib/toxicidad , Inflamación/inducido químicamente , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Nervio Ciático , Médula EspinalRESUMEN
Ifosfamide (IFO) is used for treating childhood solid tumors, but its use is limited by its adverse effects on kidneys. Morin may be used to prevent nephrotoxic and other side effects. We investigated the underlying mechanisms of the protective effects of morin on IFO induced nephrotoxicity. We used 35 male rats divided into five groups of seven: control group, morin group, IFO group, 100 mg/kg morin + IFO group and 200 mg/kg morin + IFO group. We measured kidney tissue oxidant, antioxidant and inflammatory parameters using ELISA, and apoptosis was evaluated using immunohistochemistry and real time PCR. Serum urea, creatinine and kidney injury molecule-1 (KIM-1) levels were increased by IFO treatment; elevated levels were decreased significantly by treatment with both 100 and 200 mg/kg morin. Morin treatment also decreased oxidative stress and lipid oxidation in IFO treated rats. The ameliorative effect of morin on inflammatory response was due to reduced levels of NF-κB and TNF-α. Morin also reduced NF-κB/p53 levels by increasing Bcl-2 expression in IFO treated kidneys. Morin may prevent IFO induced nephrotoxicity via the NF-κB/p53 and Bcl-2 signaling pathways.
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Ifosfamida , FN-kappa B , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Apoptosis , Flavonoides/metabolismo , Flavonoides/farmacología , Ifosfamida/toxicidad , Riñón , Masculino , FN-kappa B/metabolismo , Estrés Oxidativo , Ratas , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
The patients with hepatic alveolar echinococcosis is poorly detected due to invasive and slow growth. Thus, early diagnosis of hepatic alveolar echinococcosis is so important for patients. Circular RNAs are crucial types of the non-coding RNA. Recent studies have provided serum-derived exosomal circRNAs as potential biomarkers for detection of various diseases. The clinical importance of exosomal circRNAs in hepatic alveolar echinococcosis have never been explored before. Here, we investigated the serum-derived exosomal circRNAs in the diagnosis of hepatic alveolar echinococcosis. Firstly, High-throughput Sequencing was performed using 9 hepatic alveolar echinococcosis and 9 control samples to detect hepatic alveolar echinococcosis related circRNAs. Afterwards, bioinformatic analyzes were performed to identify differentially expressed circRNAs and pathway analyzes were performed. Finally, validation of the determined circRNAs was performed using RT-PCR. The sequencing data indicated that 59 differentially expressed circRNAs; 31 up-regulated and 28 down-regulated circRNA in hepatic alveolar echinococcosis patients. The top 5 up-regulated and down-regulated circRNAs were selected for validation by RT-qPCR assay. As a result of the verification, circRNAs that were significantly up- and down-regulated showed an expression profile consistent with the results obtained. Importantly, our findings suggested that identified exosomal circRNAs could be a potential biomarker for the detection of hepatic alveolar echinococcosis serum and may help to understand the pathogenesis of hepatic alveolar echinococcosis.
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Equinococosis Hepática/genética , Exosomas/genética , ARN Circular/sangre , Biomarcadores/sangre , Equinococosis Hepática/sangre , Redes Reguladoras de Genes , Secuenciación de Nucleótidos de Alto Rendimiento/normas , Humanos , Control de Calidad , RNA-Seq/normas , TranscriptomaRESUMEN
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.
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Nanopartículas del Metal , Contaminantes Químicos del Agua , Animales , Daphnia/metabolismo , Nanopartículas del Metal/toxicidad , Tamaño de la Partícula , Plata/metabolismo , Plata/toxicidad , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/toxicidadRESUMEN
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.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Ifosfamida , Animales , Antioxidantes/farmacología , Apoptosis , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Daño del ADN , Flavonoides , Glutatión/metabolismo , Ifosfamida/metabolismo , Ifosfamida/toxicidad , Inflamación/patología , Hígado , Estrés Oxidativo , Ratas , Superóxido Dismutasa/metabolismoRESUMEN
Deltamethrin is a type-II pyrethroid synthetic insecticide that is extensively used for controlling mosquitoes, flies, pests, and insects worldwide. This study was carried out to evaluate the likelihood protective effects of rutin, a natural antioxidant, against deltamethrin-induced liver and kidney toxicities in rats. Hepatotoxicity and nephrotoxicity were evaluated after the rats were treated orally with deltamethrin (1.28 mg/kg b.w.) alone or with rutin (25 and 50 mg/kg b.w.) for 30 days. Deltamethrin administration caused an increase in lipid peroxidation level and a decrease in activities of SOD, CAT, GPx, and GSH levels in the both tissues. Deltamethrin also increased serum ALT, AST, ALP, urea, and creatinine levels, while reduced nephrine levels in rats. In addition, deltamethrin increased the activation of inflammatory and apoptotic pathways by decreasing Bcl-2 and increasing TNF-α, NF-κB, IL-1ß, p38α MAPK, COX-2, iNOS, beclin-1, Bax, and caspase-3 protein levels and/or activities. Furthermore, deltamethrin increased mRNA expression levels of PARP-1, VEGF, and immunohistochemical expressions of c-fos in the tissues. Rutin treatment significantly improved all examined parameters and restored the liver and kidney histopathological and immunohistochemical alterations. These findings demonstrate that rutin could be used to ameliorate hepatotoxicity and nephrotoxicity associated with oxidative stress, inflammation, and apoptosis in deltamethrin-induced rats.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Rutina , Animales , Antioxidantes/metabolismo , Apoptosis , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Inflamación/inducido químicamente , Inflamación/metabolismo , Riñón/metabolismo , FN-kappa B/metabolismo , Nitrilos , Estrés Oxidativo , Piretrinas , Ratas , Ratas Sprague-DawleyRESUMEN
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.
Asunto(s)
Encéfalo/fisiología , Proteínas de Peces/metabolismo , Calor/efectos adversos , Oncorhynchus mykiss/fisiología , Agua/química , Animales , Apoptosis/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteínas de Choque Térmico/metabolismo , Estrés Oxidativo/genética , Proteínas Proto-Oncogénicas c-fos/metabolismoRESUMEN
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.
Asunto(s)
Cloropirifos , Hesperidina , Animales , Antioxidantes/metabolismo , Apoptosis , Autofagia , Hesperidina/farmacología , Inflamación/metabolismo , Hígado , Masculino , Estrés Oxidativo , Poli(ADP-Ribosa) Polimerasa-1 , Inhibidores de Poli(ADP-Ribosa) Polimerasas/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Ratas , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Docetaxel (DTX) is a chemotherapeutic agent used in the treatment of various malignancies but is often associated with central and peripheral neurotoxicity. The aim of this study was to investigate the neuroprotective effect of silymarin (SLM) against DTX-induced central and peripheral neurotoxicities in rats. Rats received 25 and 50 mg/kg body weight SLM orally for seven consecutive days after receiving a single injection of 30 mg/kg body weight DTX on the first day. SLM significantly decreased brain lipid peroxidation level and ameliorated brain glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in DTX-administered rats. SLM attenuated levels of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), glial fibrillary acidic protein (GFAP) and activity of p38α mitogen-activated protein kinase (p38α MAPK) whereas caused an increase in levels of neural cell adhesion molecule (NCAM) in the brain and sciatic nerve of DTX-induced rats. In addition, SLM improved the histological structure of the brain and sciatic nerve tissues and decreased the expression of c-Jun N-terminal kinase (JNK) in the sciatic nerve whereas increased cyclic AMP response element binding protein (CREB) expression in the brain induced by DTX. Additionally, SLM markedly up-regulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and B-cell lymphoma-2 (Bcl-2) and downregulated the expression of Bcl-2 associated X protein (Bax) in the brain and sciatic nerve tissues of DTX-induced rats. Our results show that SLM can protect DTX-induced brain and sciatic nerve injuries by enhancing the antioxidant defense system and suppressing apoptosis and inflammation.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Docetaxel/farmacología , Inflamación/prevención & control , Estrés Oxidativo/efectos de los fármacos , Nervios Periféricos/efectos de los fármacos , Sustancias Protectoras/farmacología , Silimarina/farmacología , Animales , Hemo Oxigenasa (Desciclizante)/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ratas , Transducción de Señal/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismoRESUMEN
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.