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1.
Ann Agric Environ Med ; 27(3): 368-373, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32955216

RESUMO

INTRODUCTION: Chlorpyrifos (CPF) is a organophosphate insecticide widely used in agriculture with attendant adverse health outcomes. Chronic exposure to CPF induces oxidative stress and elicits harmful effects, including hepatic dysfunction. Molecular hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. OBJECTIVE: The aim of this study was to determine whether the intake of hydrogen-rich water (HRW) could protect rats from hepatotoxicity caused by sub-chronic exposure to CPF. MATERIAL AND METHODS: Rats were treated with hydrogen-rich water by oral intake for 8 weeks. Biochemical indicators of liver function, SOD and CAT activity, GSH and MDA levels were determined by the spectrophotometric method. Liver cell damage induced by CPF was evaluated by histopathological and electron microscopy analysis. PCR array analysis was performed to investigated the effects of molecular hydrogen on the regulation of oxidative stress related genes. RESULTS: Both the hepatic function tests and histopathological analysis showed that the liver damage induced by CPF could be ameliorated by HRW intake. HRW intake also attenuated CPF induced oxidative stress, as evidenced by restored SOD activities and MDA levels. The results of PCR Array identified 12 oxidative stress-related genes differentially expressed after CPF exposure, 8 of chich, including the mitochondrial Sod2 gene, were significantly attenuated by HRW intake. The electron microscopy results indicated that the mitochondrial damage caused by CPF was alleviated after HRW treatment. CONCLUSIONS: The results obtained suggest that HRW intake can protect rats from CPF induced hepatotoxicity, and the oxidative stress signaling and the mitochondrial pathway may be involved in the protection of molecular hydrogen.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Clorpirifos/toxicidade , Hidrogênio/farmacologia , Inseticidas/toxicidade , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Relação Dose-Resposta a Droga , Masculino , Estresse Oxidativo/genética , Ratos , Ratos Wistar
2.
Oxid Med Cell Longev ; 2020: 8384742, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32963703

RESUMO

H2 has shown anti-inflammatory and antioxidant ability in many clinical trials, and its application is recommended in the latest Chinese novel coronavirus pneumonia (NCP) treatment guidelines. Clinical experiments have revealed the surprising finding that H2 gas may protect the lungs and extrapulmonary organs from pathological stimuli in NCP patients. The potential mechanisms underlying the action of H2 gas are not clear. H2 gas may regulate the anti-inflammatory and antioxidant activity, mitochondrial energy metabolism, endoplasmic reticulum stress, the immune system, and cell death (apoptosis, autophagy, pyroptosis, ferroptosis, and circadian clock, among others) and has therapeutic potential for many systemic diseases. This paper reviews the basic research and the latest clinical applications of H2 gas in multiorgan system diseases to establish strategies for the clinical treatment for various diseases.


Assuntos
Hidrogênio/administração & dosagem , Hidrogênio/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Betacoronavirus , Infecções por Coronavirus/terapia , Metabolismo Energético/efeitos dos fármacos , Humanos , Estresse Oxidativo/efeitos dos fármacos , Pandemias , Pneumonia Viral/terapia , Substâncias Protetoras/farmacologia
3.
Braz J Med Biol Res ; 53(10): e9183, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32901688

RESUMO

H1N1 virus-induced excessive inflammatory response contributes to severe disease and high mortality rates. There is currently no effective strategy against virus infection in lung. The present study evaluated the protective roles of a natural compound, lapiferin, in H1N1 virus-induced pulmonary inflammation in mice and in cultured human bronchial epithelial cells. Initially, Balb/C mice were grouped as Control, H1N1 infection (intranasally infected with 500 plaque-forming units of H1N1 virus), lapiferin (10 mg/kg), and H1N1+lapiferin (n=10/group). Lung histology, expression of inflammatory factors, and survival rates were assessed after 14 days of exposure. Administration of lapiferin significantly alleviated the virus-induced inflammatory infiltrate in lung tissues. Major pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, were decreased at both mRNA and protein levels by lapiferin administration in the lung homogenate. Lapiferin also reduced inflammatory cell numbers in bronchoalveolar fluid. Mechanistically, lapiferin suppressed the transcriptional activity and protein expression of NF-κB p65, causing inhibition on NF-κB signaling. Pre-incubation of human bronchial epithelial cells with an NF-κB signaling specific activator, ceruletide, significantly blunted lapiferin-mediated inhibition of pro-inflammatory cytokines secretion in an air-liquid-interface cell culture experiment. Activation of NF-κB signaling also blunted lapiferin-ameliorated inflammatory infiltrate in lungs. These results suggested that lapiferin was a potent natural compound that served as a therapeutic agent for virus infection in the lung.


Assuntos
Vírus da Influenza A Subtipo H1N1 , NF-kappa B/metabolismo , Pneumonia , Substâncias Protetoras/farmacologia , Sesquiterpenos/farmacologia , Animais , Citocinas , Humanos , Inflamação , Camundongos , Transdução de Sinais
4.
Ecotoxicol Environ Saf ; 205: 111376, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32961488

RESUMO

Deoxynivalenol (DON) is extensively detected in many kinds of foods and feeds to harm human and animal health. This research aims to investigate the effect of chlorogenic acid (CGA) on alleviating inflammation and apoptosis of swine jejunal epithelial cells (IPEC-J2) triggered by DON. The results demonstrated that cell viability was decreased when DON concentrations increased or incubation time expanded. The pretreatment with CGA (40 µg/mL) for 1 h increased cell viability, decreased lactate dehydrogenase (LDH) release and apoptosis in cells triggered by DON at 0.5 µg/mL for 6 h, compared with the DON alone-treated cells. Moreover, the mRNA abundances of IL-8, IL-6, TNF-α, COX-2, caspase-3, Bax and ASCT2 genes, and protein expressions of COX-2, Bax and ASCT2 were significantly down-regulated; while the mRNA abundances of ZO-1, claudin-1, occludin, PePT1 and GLUT2 genes, and protein expressions of ZO-1, claudin-1 and PePT1 were significantly up-regulated in the CGA + DON group, compared with the DON alone group. This study indicated that CGA pretreatment alleviated cytotoxicity, inflammation and apoptosis in DON-triggered IPEC-J2 cells, and protected intestinal cell integrity from DON damages.


Assuntos
Ácido Clorogênico/farmacologia , Substâncias Protetoras/farmacologia , Tricotecenos/toxicidade , Animais , Apoptose/efeitos dos fármacos , Caspase 3 , Contagem de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ácido Clorogênico/metabolismo , Células Epiteliais/efeitos dos fármacos , Inflamação/metabolismo , Intestinos/efeitos dos fármacos , Ocludina/genética , Suínos
5.
Environ Health Prev Med ; 25(1): 53, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917140

RESUMO

BACKGROUND: Pilea umbrosa (Urticaceae) is used by local communities (district Abbotabad) for liver disorders, as anticancer, in rheumatism and in skin disorders. METHODS: Methanol extract of P. umbrosa (PUM) was investigated for the presence of polyphenolic constituents by HPLC-DAD analysis. PUM (150 mg/kg and 300 mg/kg) was administered on alternate days for eight weeks in rats exposed with carbon tetrachloride (CCl4). Serum analysis was performed for liver function tests while in liver tissues level of antioxidant enzymes and biochemical markers were also studied. In addition, semi quantitative estimation of antioxidant genes, endoplasmic reticulum (ER) induced stress markers, pro-inflammatory cytokines and fibrosis related genes were carried out on liver tissues by RT-PCR analysis. Liver tissues were also studied for histopathological injuries. RESULTS: Level of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and glutathione (GSH) decreased (p < 0.05) whereas level of thiobarbituric acid reactive substance (TBARS), H2O2 and nitrite increased in liver tissues of CCl4 treated rat. Likewise increase in the level of serum markers; alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and total bilirubin was observed. Moreover, CCl4 caused many fold increase in expression of ER stress markers; glucose regulated protein (GRP-78), x-box binding protein1-total (XBP-1 t), x-box binding protein1-unspliced (XBP-1 u) and x-box binding protein1-spliced (XBP-1 s). The level of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) was aggregated whereas suppressed the level of antioxidant enzymes; γ-glutamylcysteine ligase (GCLC), protein disulfide isomerase (PDI) and nuclear erythroid 2 p45-related factor 2 (Nrf-2). Additionally, level of fibrosis markers; transforming growth factor-ß (TGF-ß), Smad-3 and collagen type 1 (Col1-α) increased with CCl4 induced liver toxicity. Histopathological scrutiny depicted damaged liver cells, neutrophils infiltration and dilated sinusoids in CCl4 intoxicated rats. PUM was enriched with rutin, catechin, caffeic acid and apigenin as evidenced by HPLC analysis. Simultaneous administration of PUM and CCl4 in rats retrieved the normal expression of these markers and prevented hepatic injuries. CONCLUSION: Collectively these results suggest that PUM constituted of strong antioxidant chemicals and could be a potential therapeutic agent for stress related liver disorders.


Assuntos
Tetracloreto de Carbono/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fibrose/tratamento farmacológico , Inflamação/tratamento farmacológico , Substâncias Protetoras/farmacologia , Urticaceae/química , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fibrose/genética , Inflamação/genética , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
6.
Ecotoxicol Environ Saf ; 204: 111049, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32758698

RESUMO

Recent studies identified a novel programmed and regulated cell death that was characterized by a necrotic cell death morphology, termed necroptosis. Lead (Pb) is known as a persistent inorganic environmental pollutant that affects the health of humans and animals worldwide. However, there are no detailed reports of Pb-induced necroptosis of immune tissue. Selenium (Se) is a trace element that antagonizes the toxicity of heavy metals. Here, chickens were randomly divided into four groups, treated with Pb ((CH3OO)2Pb, 150 mg/kg) and/or Se (Na2SeO3, 2 mg/kg), aim to study the effect and mechanism of necroptosis in Pb-induced spleen injury and the antagonistic effects of Se on Pb toxicity. Our results showed that Pb exposure evidently increased the accumulation of Pb in spleen and caused necroptosis by upregulating the expression of RIP1, RIP3 and MLKL, and decreasing Caspase8 expression. Meanwhile, Pb treatment inhibited the activities of SOD, GPX, and CAT, caused the accumulation of NO and MDA, and induced oxidative stress, which promoted the expression of MAPK/NF-κB pathway genes (ERK, JNK, P38, NF-κB and TNF-α) and activated HSPs (HSP27, HSP40, HSP60, HSP70 and HSP90). However, the increased content of Pb in spleen and Pb-caused necroptosis were inhibited by Se cotreatment. Overall, we conclude that Se can prevent Pb-induced necroptosis by restoring antioxidant functions and blocking the MAPK/NF-κB pathway and HSPs activation in chicken spleen.


Assuntos
Galinhas/fisiologia , Poluentes Ambientais/toxicidade , Chumbo/toxicidade , Necroptose/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Selênio/farmacologia , Baço/efeitos dos fármacos , Animais , Proteínas Aviárias/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Proteínas de Choque Térmico/metabolismo , NF-kappa B/metabolismo , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Baço/fisiologia
7.
J Environ Pathol Toxicol Oncol ; 39(2): 149-157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749124

RESUMO

Heavy-metal toxicity imposes a potential worldwide threat to the environment and humans. Cadmium, mercury, lead, and arsenic are nonessential toxic heavy metals that are most frequently involved in environmental and health hazards. Conventional chelating agents are unsuitable for subchronic and chronic heavy-metal toxicities. Scientific literature reveals that Spirulina (Arthrospira), a photosynthetic filamentous cyanobacterium that is generally known as blue-green algae, alleviates experimentally induced heavy-metal toxicity. The present review attempts to summarize such studies regarding cadmium, mercury, lead, and arsenic toxicity. A total of 58 preclinical studies demonstrate the alleviative effect of Spirulina against experimental arsenic, cadmium, lead, and mercury toxicities. Five clinical studies reported protective effects of Spirulina against arsenic toxicity in humans. Clinical studies against three heavy metals were not found in the literature. The present literature study appears to show that Spirulina possesses promising heavy-metal toxicity-ameliorative effects that are mainly attributed to its intrinsic antioxidant activity.


Assuntos
Intoxicação por Metais Pesados/prevenção & controle , Metais Pesados/toxicidade , Substâncias Protetoras/farmacologia , Spirulina , Animais , Arsênico/toxicidade , Suplementos Nutricionais , Intoxicação por Metais Pesados/tratamento farmacológico , Humanos
8.
J Med Life ; 13(2): 138-143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742504

RESUMO

Treatment with anticancer drugs such as cyclophosphamide can harm the male reproductive system. Vitamin C and zinc are micronutrients with antioxidant activity and are the essential components of semen. Therefore, this study aimed to evaluate whether cyclophosphamide-exposed mice can recover from fertility with vitamin C and zinc therapy. In this experimental study, fifty male mice were divided into five groups. Groups 1-4 received cyclophosphamide (100 mg/kg, once a week for eight weeks). Also, group 2 received zinc (200 mg/kg), group 3 received vitamin C (300 mg/kg), group 4 received zinc and vitamin C (200 mg/kg and 300 mg/kg, respectively), five times per week for eight weeks, and group 5 received normal saline once a week and water five days a week for eight weeks. The data collected were statistically analyzed using SPSS 22. Results showed a significant increase in mount latency and a significant decrease in the number of sperms in the cyclophosphamide group compared to the control group. However, mount latency has been significantly decreased in mice treated with cyclophosphamide plus zinc compared to the cyclophosphamide group. The study also showed that the sperm count in the group that received cyclophosphamide and zinc had been increased compared to the cyclophosphamide group; the other treatments have decreased mount latency and increased the sperm count compared to the group treated with cyclophosphamide but not significantly. The Tubule Differentiation Index showed an increase in the cyclophosphamide-Zinc-Vitamin C group in comparison with the cyclophosphamide group. The current study showed that zinc could improve cyclophosphamide-induced toxicity of the reproductive system in male mice.


Assuntos
Antineoplásicos/efeitos adversos , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Substâncias Protetoras/farmacologia , Reprodução/efeitos dos fármacos , Zinco/farmacologia , Animais , Ácido Ascórbico/administração & dosagem , Ciclofosfamida/efeitos adversos , Hormônios/metabolismo , Humanos , Masculino , Camundongos , Comportamento Sexual Animal/efeitos dos fármacos , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos
9.
Life Sci ; 258: 118192, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32781062

RESUMO

The present study was conducted to identify possible health - promoting effects of wogonin (Wog) on testicular dysfunction in rats caused by cadmium. Pre-treatment of cadmium chloride (Cd: 5 mg/kg b.wt.) administered rats with wogonin (10 mg/kg b.wt) resulted in significant improvement in Cd-induced decrease in body and organ (testes and epididymides) weights. Wogonin treatment significantly improved Cd-induced reduction in sperm quality and quantity, steroidogenic gene (SFI, StAR, CYP11A1, 3ß-HSD, CYP17A1 and 17ß-HSD) and protein (SF1, StAR and CYP17A1) expressions and serum testosterone levels. Wogonin treatment provided significant protection to Cd-induced aggression in testicular oxidative (elevated levels of MDA) and anti-oxidative (diminished activities of SOD, CAT and GPx) status. Wog significantly up-regulated mRNA levels of Nrf2, NQO1 and HO-1 and down-regulation of Keap1 in cadmium treated testes. Wogonin administration significantly suppressed Cd-stimulated increase in inflammatory reactions (increase in NF-κB p65 DNA, p-IKKß, TNF-α levels and decrease in IL-10 levels). Wogonin prevented apoptotic damage by enhanced protein distribution of caspase-9, caspase-3, and Bax due to Cd exposure. Furthermore, Wogonin presented significant protection to histo-morphometric changes resulted after Cd administration. Taken together, the findings of this study provided clear evidence of the therapeutic potential of Cd-induced testicular toxicity at least partly due to its antioxidant, anti-inflammatory and anti-apoptotic properties.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Cádmio/toxicidade , Flavanonas/farmacologia , Substâncias Protetoras/farmacologia , Transdução de Sinais , Testículo/patologia , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Epididimo/efeitos dos fármacos , Epididimo/patologia , Comportamento Alimentar/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônios/sangue , Inflamação/patologia , Masculino , Oxirredução , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Esteroides/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo
10.
PLoS One ; 15(8): e0236879, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790676

RESUMO

Benign prostatic hyperplasia (BPH) is a progressive pathological condition associated with proliferation of prostatic tissues, prostate enlargement, and lower-urinary tract symptoms. However, the mechanism underlying the pathogenesis of BPH is unclear. The aim of this study was to investigate the protective effects of a combination of Stauntonia hexaphylla and Cornus officinalis (SC extract) on a testosterone propionate (TP)-induced BPH model. The effect of SC extract was examined in a TP-induced human prostate adenocarcinoma cell line. Male Sprague-Dawley rats were randomly divided into 5 groups (n = 6) for in vivo experiments. To induce BPH, all rats, except those in the control group, were administered daily with subcutaneous injections of TP (5 mg/kg) and orally treated with appropriate phosphate buffered saline/drugs (finasteride/saw palmetto/SC extract) for 4 consecutive weeks. SC extract significantly downregulated the androgen receptor (AR), prostate specific antigen (PSA), and 5α-reductase type 2 in TP-induced BPH in vitro. In in vivo experiments, SC extract significantly reduced prostate weight, size, serum testosterone, and dihydrotestosterone (DHT) levels. Histologically, SC extract markedly recovered TP-induced abnormalities and reduced prostatic hyperplasia, thereby improving the histo-architecture of TP-induced BPH rats. SC extract also significantly downregulated AR and PSA expression, as assayed using immunoblotting. Immunostaining revealed that SC extract markedly reduced the 5α-reductase type 2 and significantly downregulated the expression of proliferating cell nuclear antigen. In addition, immunoblotting of B-cell lymphoma 2 (Bcl-2) family proteins indicated that SC extract significantly downregulated anti-apoptotic Bcl-2 and markedly upregulated pro-apoptotic B cell lymphoma-associated X (Bax) expression. Furthermore, SC treatment significantly decreased the Bcl-2/Bax ratio, indicating induced prostate cell apoptosis in TP-induced BPH rats. Thus, our findings demonstrated that SC extract protects against BPH by inhibiting 5α-reductase type 2 and inducing prostate cell apoptosis. Therefore, SC extract might be useful in the clinical treatment of BPH.


Assuntos
Apoptose/efeitos dos fármacos , Colestenona 5 alfa-Redutase/química , Extratos Vegetais/farmacologia , Hiperplasia Prostática/prevenção & controle , Substâncias Protetoras/uso terapêutico , Inibidores de 5-alfa Redutase/química , Inibidores de 5-alfa Redutase/farmacologia , Inibidores de 5-alfa Redutase/uso terapêutico , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colestenona 5 alfa-Redutase/metabolismo , Cornus/química , Cornus/metabolismo , Regulação para Baixo/efeitos dos fármacos , Humanos , Masculino , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Folhas de Planta/metabolismo , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/etiologia , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ranunculales/química , Ranunculales/metabolismo , Ratos , Ratos Sprague-Dawley , Propionato de Testosterona/efeitos adversos
11.
Toxicon ; 186: 182-190, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32822735

RESUMO

Snakebites produce several toxic effects in victims, such as hemorrhage, tissue necrosis, hemostatic, renal, or cardiotoxic alterations, inflammation, and death. To counteract these symptoms, antivenom is the official treatment. Although such therapy prevents death, it does not efficiently neutralize necrosis or other local effects, leading to amputation or morbidities of the affected limb. Therefore, the search for better and more efficient therapies deserves attention; further, plants have been used to ameliorate a number of diseases and medical conditions, including snakebites, for many years. Thus, the aim of this work was to evaluate the antivenom effect of the crude extract, fractions (aqueous and diethyl acetate), and subfractions derived from the aqueous fraction (P1, P2, P3, and P4) of the plant Stryphnodendron adstringens against in vitro (coagulation and proteolytic) and in vivo (edema, hemorrhage, and myotoxic) activities caused by Bothrops jararacussu venom. Overall, all extracts inhibited the toxic effect of B. jararacussu venom, but with different potencies, regardless of whether plant samples were incubated together with venom or injected before or after venom injection into animals; the crude extract and aqueous fraction were found to be the most effective. Indeed, phytochemical and mass spectrometry analysis of S. adstringens samples revealed the presence of flavonols, tannins, and saponins. In conclusion, the plant S. adstringens may represent a promising natural source of molecules to treat the toxic effects associated with envenomation by B. jararacussu snakebites.


Assuntos
Bothrops , Venenos de Crotalídeos/toxicidade , Fabaceae , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antivenenos , Edema , Hemorragia , Mordeduras de Serpentes
12.
PLoS One ; 15(8): e0237086, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764782

RESUMO

Paramylon is a novel ß-glucan that is stored by Euglena gracilis Z, which is a unicellular photosynthesizing green alga with characteristics of both animals and plants. Recent studies have indicated that paramylon functions as an immunomodulator or a dietary fiber. Currently, chronic kidney disease (CKD) is a global health problem, and there is no effective preventive treatment for CKD progression. However, paramylon may suppress the progression of CKD via the elimination of uremic toxins or modulation of gut microbiota, leading to the alleviation of inflammation. The aim of this study was to evaluate the effect of paramylon in CKD rat model. Eight-week-old male Wistar rats with a 5/6 nephrectomy were given either a normal diet or a diet containing 5% paramylon for 8 weeks. Proteinuria was measured intermittently. Serum and kidney tissues were harvested after sacrifice. We performed a renal molecular and histopathological investigation, serum metabolome analysis, and gut microbiome analysis. The results showed that paramylon attenuated renal function, glomerulosclerosis, tubulointerstitial injury, and podocyte injury in the CKD rat model. Renal fibrosis, tubulointerstitial inflammatory cell infiltration, and proinflammatory cytokine gene expression levels tended to be suppressed with paramylon treatment. Further, paramylon inhibited the accumulation of uremic toxins, including tricarboxylic acid (TCA) cycle-related metabolites and modulated a part of CKD-related gut microbiota in the CKD rat model. In conclusion, we suggest that paramylon mainly inhibited the absorption of non-microbiota-derived uremic solutes, leading to protect renal injury via anti-inflammatory and anti-fibrotic effects. Paramylon may be a novel compound that can act against CKD progression.


Assuntos
Glucanos/farmacologia , Rim/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Proteinúria/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Administração Oral , Animais , Ciclo do Ácido Cítrico/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Euglena gracilis/química , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Glucanos/isolamento & purificação , Glucanos/uso terapêutico , Humanos , Mediadores da Inflamação/metabolismo , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Rim/imunologia , Rim/patologia , Masculino , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/uso terapêutico , Proteinúria/sangue , Proteinúria/patologia , Ratos , Ratos Wistar , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/urina , Toxinas Biológicas/sangue , Toxinas Biológicas/metabolismo
13.
Chem Biol Interact ; 330: 109234, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32860823

RESUMO

Cisplatin is an antineoplastic drug well recognized for its success in the battle against several types of cancer in adult, juvenile, and child populations. Meanwhile, this drug is also famous due to its serious side effects, such as hepatotoxicity. This study evaluated the hepatoprotective effectiveness of Diphenyl Diselenide (PhSe)2 and Ebselen in a model of cisplatin-induced toxicity in juvenile rats. Juvenile Wistar rats received a single intraperitoneal (i.p) injection of cisplatin (6 mg/kg) or saline solution, at postnatal day (PND) 21. Ebselen (11 mg/kg) or (PhSe)2 (12 mg/kg) was intragastrically (i.g) administered in rats from PND 21 to PND 25. At PND 26, the blood and liver were collected for the biochemistry assays. A single administration of cisplatin was enough to alter the makers of hepatic function (an increase of AST activity) and the blood lipid profile (an increase of cholesterol and triglycerides, TG). The cisplatin-induced metabolic disruption was demonstrated by the increase of hepatic glycogen and TG contents and hexokinase, glucose-6-phosphatase, and tyrosine aminotransferase activities; a decrease of citrate synthase activity and the levels of GLUT-2. Cisplatin-induced hepatic oxidative stress was characterized by an increase in reactive oxygen species, TBARS, protein carbonyl, and Nox levels as well as the decrease in NPSH levels. Ebselen and (PhSe)2 were effective against all alterations caused by this chemotherapy medication. The present findings highlight the (PhSe)2 and Ebselen similar hepatoprotective effectiveness against cisplatin-induced disruption of metabolic homeostasis and redox balance in juvenile rats.


Assuntos
Azóis/farmacologia , Derivados de Benzeno/farmacologia , Cisplatino/toxicidade , Homeostase/efeitos dos fármacos , Fígado/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Lipídeos/sangue , Fígado/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos
14.
Chem Biol Interact ; 329: 109213, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32739323

RESUMO

Phytoestrogens are plant-derived substances with a similar structure to 17-beta-estradiol, which have protective roles in estrogen-dependent diseases. Isoflavones, the most well-known subgroup of phytoestrogens, play protective roles against chemicals-induced liver injuries through several molecular mechanisms. Hepatoprotective effects of isoflavones are, partly, associated with their antioxidant, anti-inflammatory, immunomodulatory, and anti-fibrotic properties. Besides, isoflavones can reduce gut-derived endotoxins, accelerate alcohol metabolism, stimulate detoxification of hepatotoxic chemicals, suppress the bioactivation of these chemicals, inhibit hepatocytes apoptosis, and restore autophagy activity during chemicals-induced liver diseases. This review provides a summary of the molecular mechanisms underlying the hepatoprotective effects of isoflavones. It seems that further studies are needed to investigate the hepatoprotective potential of isoflavones in patients with different stages of chemicals-induced liver injuries.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Isoflavonas/metabolismo , Substâncias Protetoras/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Inflamação/prevenção & controle , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Cirrose Hepática/metabolismo , Cirrose Hepática/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-32666147

RESUMO

Several invasive alien plants (IAP) can trigger evidently allelopathy on the seed germination and seedling growth (SgSg) of native plant species (NPS). The getting worse condition with heavy metal pollution (e.g., cadmium) can significantly impact SgSg of plant species. Silicon can offset the adverse effects of environmental pressure on the growth and development of plant species. Thus, it is important to evaluate the influences of silicon on the allelopathy of IAP on SgSg of NPS under cadmium stress to better understand the mechanism driving the successful colonization of IAP. This study focuses on the allelopathy of the infamous IAP Solidago canadensis L. (Canada goldenrod; by using leaf extracts) on SgSg of NPS Lactuca sativa L. under the separated and mixed silicon and cadmium addition. S. canadensis triggers notably allelopathy on SgSg of L. sativa and gradually upsurges with increasing leaf extract concentration. Thus, the growth performance of NPS will be gradually reduced with an increasing degree of S. canadensis invasion. Cadmium evidently declines SgSg of L. sativa due to the broken balance of plant species for nutrient absorption. The mixed S. canadensis leaf extracts and cadmium synergistically impact seed germination of L. sativa but antagonistically affect seedling growth of L. sativa. The mixed silicon and cadmium intensify the allelopathy of S. canadensis on SgSg of L. sativa probably due to the increased effective content of cadmium in plant roots under silicon addition. Thus, the mixed silicon and cadmium will be advantageous to the following invasion process of IAP largely via the depressed SgSg of NPS.


Assuntos
Alelopatia/efeitos dos fármacos , Cádmio/efeitos adversos , Alface/crescimento & desenvolvimento , Substâncias Protetoras/farmacologia , Silício/farmacologia , Poluentes do Solo/efeitos adversos , Solidago/efeitos dos fármacos , Germinação/efeitos dos fármacos , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Solidago/fisiologia
17.
Chem Biol Interact ; 328: 109193, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32668205

RESUMO

Embryonic studies have demonstrated the neurotoxic, teratogenic, and neurobehavioral toxicity of ethanol (EtOH). Although multiple mechanisms may contribute to these effects, oxidative stress has been described as the major damage pathway. In this regard, natural antioxidants have the potential to counteract oxidative stress-induced cellular damage. Therefore, the present study aimed to investigate the potential protective role of 24-epibrassinolide (24-EPI), a natural brassinosteroid with proved antioxidant properties, in EtOH-induced teratogenic effects during early zebrafish development. Embryos (~2 h post-fertilization - hpf) were exposed to 1 % EtOH, co-exposed to 24-EPI (0.01, 0.1 and 1 µM) and to 24-EPI alone (1 µM) for 24 h. Following exposure, biochemical evaluations were made at 26 hpf, developmental analysis was made throughout the embryo-larval period, and behavioural responses were evaluated at 120 hpf. Exposure to 1 % EtOH caused an increase in the number of malformations, which were diminished by 24-EPI. In addition, EtOH induced an accumulation of GSSG and consequent reduction of GSH:GSSG ratio, indicating the involvement of oxidative mechanisms in the EtOH-induced effects. These were reverted by 24-EPI as proved by the GSSG levels and GSH:GSSG ratio that returned to control values. Furthermore, exposure to EtOH resulted in behavioural deficits at 120 hpf as observed by the disrupted response to an aversive stimulus, suggesting the involvement of neurotoxic mechanisms. 24-EPI restored the behavioural deficits observed in a dose-dependent manner. The absence of effects in the embryos exposed solely to 24-EPI showed its safety during the exposure period. In conclusion, EtOH caused developmental teratogenicity and behavioural toxicity by inducing glutathione changes, which were prevented by 24-EPI.


Assuntos
Comportamento Animal , Brassinosteroides/farmacologia , Embrião não Mamífero/patologia , Etanol/toxicidade , Substâncias Protetoras/farmacologia , Esteroides Heterocíclicos/farmacologia , Teratogênese/efeitos dos fármacos , Peixe-Zebra/embriologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Embrião não Mamífero/anormalidades , Embrião não Mamífero/efeitos dos fármacos , Glutationa/metabolismo , Larva/efeitos dos fármacos , Comportamento Social
19.
PLoS One ; 15(7): e0228429, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32722679

RESUMO

Diabetes mellitus (DM) causes ototoxicity by inducing oxidative stress, microangiopathy, and apoptosis in the cochlear sensory hair cells. The natural anti-oxidant pterostilbene (PTS) (trans-3,5-dimethoxy-4-hydroxystylbene) has been reported to relieve oxidative stress and apoptosis in DM, but its role in diabetic-induced ototoxicity is unclear. This study aimed to investigate the effects of dose-dependent PTS on the cochlear cells of streptozotocin (STZ)-induced diabetic rats. The study included 30 albino male Wistar rats that were randomized into five groups: non-diabetic control (Control), diabetic control (DM), and diabetic rats treated with intraperitoneal PTS at 10, 20, or 40 mg/kg/day during the four-week experimental period (DM + PTS10, DM + PTS20, and DM + PTS40). Distortion product otoacoustic emission (DPOAE) tests were performed at the beginning and end of the study. At the end of the experimental period, apoptosis in the rat cochlea was investigated using caspase-8, cytochrome-c, and terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin end labeling (TUNEL). Quantitative real-time polymerase chain reaction was used to assess the mRNA expression levels of the following genes: CASP-3, BCL-associated X protein (BAX), and BCL-2. Body weight, blood glucose, serum insulin, and malondialdehyde (MDA) levels in the rat groups were evaluated. The mean DPOAE amplitude in the DM group was significantly lower than the means of the other groups (0.9-8 kHz; P < 0.001 for all). A dose-dependent increase of the mean DPOAE amplitudes was observed with PTS treatment (P < 0.05 for all). The Caspase-8 and Cytochrome-c protein expressions and the number of TUNEL-positive cells in the hair cells of the Corti organs of the DM rat group were significantly higher than those of the PTS treatment and control groups (DM > DM + PTS10 > DM + PTS20 > DM + PTS40 > Control; P < 0.05 for all). PTS treatment also reduced cell apoptosis in a dose-dependent manner by increasing the mRNA expression of the anti-apoptosis BCL2 gene and by decreasing the mRNA expressions of both the pro-apoptosis BAX gene and its effector CASP-3 and the ratio of BAX/BCL-2 in a dose-dependent manner (P < 0.05 compared to DM for all). PTS treatment significantly improved the metabolic parameters of the diabetic rats, such as body weight, blood glucose, serum insulin, and MDA levels, consistent with our other findings (P < 0.05 compared to DM for all). PTS decreased the cochlear damage caused by diabetes, as confirmed by DPOAE, biochemical, histopathological, immunohistochemical, and molecular findings. This study reports the first in vivo findings to suggest that PTS may be a protective therapeutic agent against diabetes-induced ototoxicity.


Assuntos
Cóclea/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Ototoxicidade/prevenção & controle , Estilbenos/farmacologia , Acústica , Animais , Peso Corporal/efeitos dos fármacos , Caspase 3/genética , Cóclea/patologia , Diabetes Mellitus Experimental/complicações , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Substâncias Protetoras/farmacologia , Ratos Wistar , Estilbenos/administração & dosagem , Estreptozocina , Proteína X Associada a bcl-2/genética
20.
Toxicon ; 185: 97-103, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32622693

RESUMO

Mycotoxins are toxic secondary metabolites produced by fungus which cause worldwide concern regarding food and feed safety. Ochratoxin A (OTA), fumonisin B1 (FB1) and deoxynivalenol (DON) are some of the main mycotoxins and oxidative stress is the main mechanism of toxicity. Thereby, this study investigates the in vitro cytoprotective effects of curcumin (CUR) and silymarin (SIL) - known for their strong antioxidant activity - in PK-15 cells exposed to OTA, FB1 and DON. Pretreatment with CUR and SIL enhanced the viability of cells exposed to the mycotoxins (P < 0.001) and attenuated reactive oxygen species (ROS) formation by DON (P < 0.01), partially reduced ROS formation by FB1 (P < 0.001), but not OTA. CUR significantly decreased apoptosis in cells exposed to DON (P < 0.01) but was not able to prevent apoptosis in cells exposed to OTA and FB1. Whereas SIL was able to prevent apoptosis in PK-15 cells exposed to FB1 and DON (P < 0.01) but was not able to decrease apoptosis in cells exposed to OTA. In summary, these data indicate that curcumin and silymarin are able to provide cytoprotection against toxicity induced by OTA, FB1 and DON in PK-15 cells.


Assuntos
Curcumina/farmacologia , Micotoxinas/toxicidade , Substâncias Protetoras/farmacologia , Silimarina/farmacologia , Apoptose , Sobrevivência Celular , Fumonisinas/toxicidade , Fungos , Ocratoxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Tricotecenos/toxicidade
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