RESUMO
Global aflatoxin contamination of agricultural commodities is of the most concern in food safety and quality. This study investigated the hepatoprotective effect of 80% methanolic leaf extract of Annona senegalensis against aflatoxin B1 (AFB1)-induced toxicity in rats. A. senegalensis has shown to inhibit genotoxicity of aflatoxin B1 in vitro. The rats were divided into six groups including untreated control, aflatoxin B1 only (negative control); curcumin (positive control; 10 mg/kg); and three groups receiving different doses (100 mg/kg, 200 mg/kg, and 300 mg/kg) of A. senegalensis extract. The rats received treatment (with the exception of untreated group) for 7 days prior to intoxication with aflatoxin B1. Serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, and creatinine were measured. Hepatic tissues were analysed for histological alterations. Administration of A. senegalensis extract demonstrated hepatoprotective effects against aflatoxin B1-induced toxicity in vivo by significantly reducing the level of serum aspartate aminotransferase and alanine aminotransferase and regenerating the hepatocytes. No significant changes were observed in the levels of alkaline phosphatase, lactate dehydrogenase, and creatinine for the AFB1 intoxicated group, curcumin+AFB1 and Annona senegalensis leaf extract (ASLE)+AFB1 (100 mg/kg, 200 mg/kg, and 300 mg/kg body weight [b.w.]) treated groups. Annona senegalensis is a good candidate for hepatoprotective agents and thus its use in traditional medicine may at least in part be justified.Contribution: The plant extract investigated in this study can be used in animal health to protect the organism from toxicity caused by mycotoxins.
Assuntos
Annona , Curcumina , Ratos , Animais , Aflatoxina B1/toxicidade , Curcumina/farmacologia , Alanina Transaminase/farmacologia , Fosfatase Alcalina/farmacologia , Creatinina/farmacologia , Fígado , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Aspartato Aminotransferases/farmacologia , Lactato DesidrogenasesRESUMO
This study investigated the hepatoprotective effects of Juncus effusus (J. effusus) and Carbonized J. effusus against liver injury caused by D-galactosamine (D-GalN) in mice. J. effusus and Carbonized J. effusus were administered by gavage once daily starting seven days before the D-GalN treatment. The results of the study indicated that J. effusus and Carbonized J. effusus suppressed the D-GalN-induced generation of serum alanine transaminase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) was observed. The values of superoxide dismutase (SOD) exhibited an increase. In addition, J. effusus and Carbonized J. effusus promoted the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NADPH quinone oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1) as well as the mRNA expression of Nrf2, HO-1, NQO-1 and Glutamate cysteine ligase catalytic subunit (GCLC). The compressed Carbonized J. effusus demonstrated the optimum impact. These results suggest that J. effusus and Carbonized J. effusus protect against D-GalN-induced acute liver injury through the activation of the Nrf2 pathway.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Galactosamina , Extratos Vegetais , Animais , Camundongos , Alanina Transaminase/metabolismo , Alanina Transaminase/farmacologia , Antioxidantes/farmacologia , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Galactosamina/toxicidade , Galactosamina/metabolismo , Lipopolissacarídeos/farmacologia , Fígado , Fator 2 Relacionado a NF-E2/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
Bromodeoxyuridine (BrdU) is used in studies related to cell proliferation and neurogenesis. The multiple intraperitoneal injections of this molecule could favor liver function profile changes. In this study, we evaluate the systemic and hepatocellular impact of BrdU in male adult Wistar rats in 30 %-partial hepatectomy (PHx) model. The rats received BrdU 50 mg/Kg by intraperitoneal injection at 0.5, 1, 2, 3, 6, 9 and 16 days after 30 %-PH. The rats were distributed into four groups as follows, control, sham, PHx/BrdU(-) and PHx/BrdU(+). On day 16, we evaluated hepatocellular nuclei and analyzed histopathological features by haematoxylin-eosin stain and apoptotic profile was qualified by caspase-3 presence. The systemic effect was evaluated by liver markers such as alanine transferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (AP), bilirubin, total proteins and serum albumin content. The statistical analysis consisted of a student t-test and one-way ANOVA. BrdU did not induce apoptosis or hepatocellular damage in male rats. Multiple administrations of BrdU in male rats did not induce significant decrease body weight, but increased serum ALT and LDH levels were found. Our results show that the BrdU does not produce hepatocellular damage.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratos , Masculino , Animais , Ratos Wistar , Bromodesoxiuridina/farmacologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fígado/patologia , Alanina Transaminase/metabolismo , Alanina Transaminase/farmacologia , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/farmacologiaRESUMO
Heavy metals from slag waste (HMSWs) have attracted much attention because of their serious toxicity to the environment and human organs, especially hepatotoxicity. The aim of this study was to explore the effects of different HMSWs exposure on mitochondrial lipid peroxidation, microsomal drug metabolizing enzyme activities as well as their relationship in the rat liver injury. Based on toxicogenomic analysis, heavy metals including iron, copper, cobalt, nickel and manganese, might interfere with pathophysiological processes such as oxidative stress, cell death, and energy metabolism regulation in vivo, and participate in the regulation of HIF-1 signaling pathway, peroxisomes, drug metabolism-cytochrome P450, ferroptosis, and other signaling pathways. HMSWs exposure caused weight loss, and significantly increased lactate dehydrogenase (LDH), malondialdehyde (MDA), alanine transaminase (ALT), and aspartate transaminase (AST) in different groups of rat liver, suggesting the presence of mitochondrial lipid peroxidation damage. In addition, the ratios of AST/ALT and ALT/LDH were down-regulated, especially the ALT/LDH ratios were less than 1, indicating that hepatic ischemic injury occurred in the process of liver injury. The superoxide dismutase (SOD) and mitochondrial membrane potential (MMP) activities in rats also showed significant decreases, indicating the occurrence of hepatic oxidative/antioxidant dysfunction imbalance. Further decision tree analysis of live biochemical abnormalities suggested that AST > 58.78 U/gprot and MDA > 173.2 nmol/mgprot could be used for hepatotoxicity warning. Liver microsomal cytochrome P4501A2 (CYP1A2) and 3A1 (CYP3A1) enzymes were also involved in the hepatotoxic process of heavy metals. These results suggest that lipid peroxidation damage and metabolic damage in liver mitochondria and peroxisomes, may be one of the key events in heavy metal-induced liver injury.
Assuntos
Antioxidantes , Doença Hepática Induzida por Substâncias e Drogas , Ratos , Humanos , Animais , Peroxidação de Lipídeos , Antioxidantes/metabolismo , Estresse Oxidativo , Fígado/metabolismo , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/farmacologia , Ferro/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismoRESUMO
The aim of current work was able to show the oxidant effect of cancer cells found in any part of the body on the liver and to investigate the possible protective effect of deuterium-depleted water (DDW) on this oxidant effect by determining of some liver parameters. Ehrlich ascites tumor bearing BALB/c mice were used for this purpose. BALB/c mice were selected randomly and divided into four groups (n = 5 in each group) as control group, tumor group, control+DDW group, tumor+DDW group, fifteen days after tumor cell injection, liver tissue samples were taken for all groups. In the tumor group, liver lipid peroxidation, sialic acid and protein carbonyl levels, xanthine oxidase, myeloperoxidase, catalase, gamma-glutamyl transferase, sorbitol dehydrogenase, glutathione peroxidase and glutathione reductase activities, were significantly higher than those in the control group while glutathione levels and paraoxonase1, sodium potassium ATPase, glutathione-S-transferase, alanine transaminase and aspartate transaminase activities decreased significantly. Compared with the tumor group, the changes in all parameters except sialic acid, catalase, alanine transaminase and aspartate transaminase were reversed in the DDW given tumor groups, while sialic acid and catalase values continued to increase, and alanine transaminase and aspartate transaminase values continued to decrease. In conclusion, the consumption of DDW may be beneficial and protective against excessive oxidative stress in cancer complications.
Assuntos
Água Potável , Camundongos , Animais , Catalase/metabolismo , Alanina Transaminase/metabolismo , Alanina Transaminase/farmacologia , Água Potável/metabolismo , Deutério/metabolismo , Deutério/farmacologia , Ácido N-Acetilneuramínico/metabolismo , Ácido N-Acetilneuramínico/farmacologia , Estresse Oxidativo , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/farmacologia , Peroxidação de Lipídeos , Antioxidantes/farmacologia , Glutationa/metabolismo , Fígado/patologia , Glutationa Transferase , Oxidantes/metabolismo , Oxidantes/farmacologia , Superóxido Dismutase/metabolismoRESUMO
Background: The purpose of this study is to explore the effect of carbohydrate only or carbohydrate plus protein supplementation on endurance capacity and muscle damage. Methods: Ten recreationally active male runners (VO2max: 53.61 ± 3.86 ml/kg·min) completed run-to-exhaustion test three times with different intakes of intervention drinks. There was a 7-day wash-out period between tests. Each test started with 60 minutes of running at 70% VO2max (phase 1), followed by an endurance capacity test: time-to-exhaustion running at 80% VO2max (phase 2). Participants randomly ingested either 1) 0.4 g/kg BM carbohydrate before phase 1 and before phase 2 (CHO+CHO), 2) 0.4 g/kg BM protein before phase 1 and 0.4 g/kg BM carbohydrate before phase 2 (PRO+CHO), or 3) 0.4 g/kg BM carbohydrate before phase 1 and 0.4 g/kg BM protein before phase 2 (CHO+PRO). All subjects ingested carbohydrate (CHO) 1.2 g/kg BM during phase 1, and blood samples were obtained before, immediately, and 24 h after exercise for measurements of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), and myoglobin (MB). Results: There was no significant difference in time to exhaustion between the three supplement strategies (CHO+CHO: 432 ± 225 s; PRO+CHO: 463 ± 227 s; CHO+PRO: 461 ± 248 s). However, ALT and AST were significantly lower in PRO+CHO than in CHO+CHO 24 h after exercise (ALT: 16.80 ± 6.31 vs. 24.39 ± 2.54 U/L; AST: 24.06 ± 4.77 vs. 31.51 ± 7.53 U/L, p < 0.05). MB was significantly lower in PRO+CHO and CHO+PRO than in CHO+CHO 24 h after exercise (40.7 ± 15.2; 38.1 ± 14.3; 64.3 ± 28.9 ng/mL, respectively, p < 0.05). CK increased less in PRO+CHO compared to CHO+CHO 24 h after exercise (404.22 ± 75.31 VS. 642.33 ± 68.57 U/L, p < 0.05). Conclusion: Carbohydrate and protein supplement strategies can reduce muscle damage caused by endurance exercise, but they do not improve endurance exercise capacity.
Assuntos
Carboidratos da Dieta , Resistência Física , Alanina Transaminase/metabolismo , Alanina Transaminase/farmacologia , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/farmacologia , Creatina Quinase , Estudos Cross-Over , Proteínas Alimentares , Método Duplo-Cego , Humanos , Masculino , Músculo Esquelético , MioglobinaRESUMO
This study aimed to investigate the effect of using menbutone in addition to ammonium molybdate on liver enzymes in sheep naturally poisoned with copper. Merino lambs (n = 30), naturally poisoned with copper and which also had high liver enzyme levels, were divided into two groups, each with 15 lambs. The AM + MEN group received ammonium molybdate and menbutone and the AM group received only ammonium molybdate solution. Both groups received 1.7% ammonium molybdate solution (1 mL per 10 kg body weight [BW]) subcutaneously on 0, 2nd and 4th days of the study. Menbutone (Genabil®, Boehringer Ingelheim, Germany) was administered intramuscularly at a dose of 10 mg/kg BW on days 0 and 2, in addition to ammonium molybdate in the AM + MEN group. Blood samples were collected on days 0 and 7, and aspartate aminotransferase (AST), gamma-glutamyltranspeptidase (GGT) and creatinine levels were evaluated. Over 7 days, AST levels decreased from 351.04 ± 63.50 IU/L to 286.40 ± 55.68 IU/L in the AM group (P > 0.05) and from 425.00 ± 119.25 IU/L to 240.83 ± 29.62 IU/L in the AM + MEN group (P ≤ 0.05). GGT levels decreased from 121.16 ± 15.88 IU/L to 110.39 ± 10.13 IU/L in the AM group (P > 0.05) and 124.52 ± 15.50 to 98.60 ± 9.08 IU/L in the AM + MEN group (P ≤ 0.05). Based on these findings, the use of menbutone, in addition to ammonium molybdate, has significantly reduced the level of liver enzymes.
Assuntos
Cobre , Molibdênio , Ovinos , Animais , Cobre/farmacologia , Molibdênio/farmacologia , Aspartato Aminotransferases/farmacologia , FígadoRESUMO
OBJECTIVE: Antioxidant therapy is a promising treatment option for non-alcoholic fatty liver disease (NAFLD) after failure of lifestyle modification. We aimed to explore the efficacy of combined vitamin E and C therapy compared to no treatment for NAFLD. METHODS: A literature search was performed in Ovid Embase, Ovid Medline, PubMed, Cochrane Library, Scopus, and Web of Science from inception to 28th April 2020. A systematic review and meta-analysis were conducted on randomized controlled trials that assessed vitamin E and C co-treatment in NAFLD. Quality of evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Assessed outcomes were changes in imaging findings, histological features, and serum transaminases. Subgroup analyses that compared adult versus children were further explored. RESULTS: Four studies (n=260) satisfied our eligibility criteria. Vitamin co-treatment did not improve ultrasonographic liver brightness, histological parameters of hepatocyte injury (steatosis, lobular inflammation, and ballooning), fibrosis grading (standardized mean difference [SMD ]: 0.02, 95% CI: -0.40 to 0.45, I2=13%), serum aspartate transaminase (mean difference [MD]: -0.05, 95% CI: -2.59 to 2.50, I2=0%), and serum alanine transaminase (MD: 2.82, 95% CI: -2.11 to 7.76, I2=57%). Subgroup stratifications illustrated similar findings. CONCLUSION: Vitamin co-treatment may have limited efficacy in NAFLD. However, we have little confidence in our effect estimates due to bias and other major constraints.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Alanina Transaminase/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/farmacologia , Criança , Humanos , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina E/farmacologia , Vitamina E/uso terapêutico , VitaminasRESUMO
In order to explore the effect and mechanism of Aornia mealnocarpa Elliot anthocyanins (AMA) at the cellular level on hepatic fibrosis (HF), molecular docking, RT-PCR and Western Blotting were used to explore the molecular mechanism and the effects of different doses AMA on HSC-T6 cells by TGF-ß1 induction. The results showed that the binding energy of anthocyanins on TGF-ß1 (PDB ID: 3KFD) was in the range of -9.5 to 8.6 kcal/mol, with good low energy parameters and binding positions. AMA could effectively inhibit the expressions of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total serum bilirubin (TSB), and improved the expressions of total protein (TP) and albumin (ALB). RT-PCR and Western bloting results showed that AMA could inhibited the secretion of inflammatory cytokines IL-1, IL-6, TNF-α and COX-2, and inhibit the expression of TGF-ß1, P-Smad2, α-SMA and Collagen I in TGF-ß /Smad signaling pathway. This study revealed the AMA's inhibition effects and mechanism of malignant biological behavior of HSC-T6 cells, in order to provide theoretical basis for the prevention and treatment of HF by Aronia melanocarpa Elliot.
Assuntos
Photinia , Fator de Crescimento Transformador beta1 , Alanina Transaminase/metabolismo , Albuminas/farmacologia , Fosfatase Alcalina/metabolismo , Antocianinas/metabolismo , Antocianinas/farmacologia , Antocianinas/uso terapêutico , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/farmacologia , Aspartato Aminotransferases/uso terapêutico , Bilirrubina/metabolismo , Colágeno Tipo I/metabolismo , Ciclo-Oxigenase 2/metabolismo , Interleucina-1/metabolismo , Interleucina-1/farmacologia , Interleucina-1/uso terapêutico , Interleucina-6/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Cirrose Hepática/prevenção & controle , Simulação de Acoplamento Molecular , Photinia/metabolismo , Transdução de Sinais , Proteínas Smad/metabolismo , Proteínas Smad/farmacologia , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Sorafenib is the standard treatment used in the advanced stages of HCC. Cell therapy with mesenchymal stem cells (MSCs)-based cell therapy has proven effective in immune regulation and tumour growth inhibition. OBJECTIVES: In this study, we investigated the anti-inflammatory effect of MSCs on HCC xenografts. METHODS: Human HepG2 cell lines were subcutaneously implanted into the flank of 12 nude mice, divided into three groups: the control group, the IV group (intravenous MSCs injection) and the local group (local MSCs injection). Mice were sacrificed 6 weeks after tumour implantation, and tumours were resected entirety. Quantitative real-time polymerase chain reaction (qRT-PCR) measured the gene expression of inflammatory markers, including tumour necrosis factor-α (TNF-α), interleukin (IL)-1α and IL-10. Aspartate transaminase (AST), alanine transaminase (ALT) and urea levels were measured using spectrophotometry to ensure the safety of MSC therapy. RESULTS: Gene expressions for all three inflammatory markers were reduced in both MSCs groups compared to the control group. AST, ALT and urea levels remained in normal ranges. CONCLUSIONS: MSC therapy can reduce inflammation in HCC xenograft mouse models.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Doenças dos Roedores , Alanina Transaminase/metabolismo , Alanina Transaminase/farmacologia , Alanina Transaminase/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/farmacologia , Aspartato Aminotransferases/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/veterinária , Modelos Animais de Doenças , Xenoenxertos , Humanos , Interleucina-10/metabolismo , Interleucina-10/farmacologia , Interleucina-10/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/veterinária , Transplante de Células-Tronco Mesenquimais/veterinária , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Nus , Sorafenibe/metabolismo , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismoRESUMO
In this original article, we aimed to assess the ameliorative role of Cyanus depressus (CD) plant ethanolic extract treatment of streptozotocin (STZ)-induced liver, kidney, and pancreas damage in rats. The rats were divided into five groups (n = 7): control, CD, Diabetes mellitus (DM), DM + CD, and DM + glibenclamide (Gly). The DM groups were injected with a single dose of 50 mg/kg STZ intraperitoneally (i.p.). While the CD and DM + CD groups received 400 mg/kg/day intragastrically for 21 days, the DM + Gly group received 3 mg/kg/day of Gly intragastrically throughout the experiment. Statistically significance was accepted as p < .05. According to our liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) data, quinic acid, cosmosiin, nicotiflorin, apigenin, and protocatechuic acid were the major compounds, in descending order. Weekly blood glucose, serum glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and urea, malondialdehyde (MDA) (liver and pancreas), and blood glycosylated hemoglobin % (HbA1c %) were significantly decreased, whereas finally live body weights (LBWs), reduced glutathione (GSH), glutathione S-transferase (GST) and catalase (CAT) (pancreas), and pancreatic islet diameter and area were increased significantly in the CD-treated diabetic group. Moreover, CD administration was found to be effective in the protection of the histology of the liver, kidneys, and pancreatic islets in the STZ-induced rats. Consequently, we concluded that CD administration reduces hyperglycemia, oxidative stress, and histopathology in STZ-induced experimental rats by improving antioxidant defenses. PRACTICAL APPLICATIONS: Today, the prevalence of diabetes is increasing rapidly throughout the world and it causes complications such as kidney damage, blindness, amputations, and cardiovascular diseases. Despite medical technological advances, people's interest in medicinal herbal products is gradually increasing. Biochemical and histopathological findings showed that the use of the plant CD at the determined dose (400 mg/kg/day) in rats with DM by STZ had strong antioxidant and antidiabetic effects. CD may have a drug potential in preventing DM and its complications because of its phytochemical content including some phenolic acids such as quinic acid, cosmosiin, nicotiflorin, apigenin, and protocatechuic acid. Isolation of bioactive compounds from CD and investigation of their therapeutic effects could be planned as further studies.
Assuntos
Diabetes Mellitus Experimental , Extratos Vegetais , Alanina Transaminase/metabolismo , Alanina Transaminase/farmacologia , Alanina Transaminase/uso terapêutico , Animais , Antioxidantes/farmacologia , Apigenina/metabolismo , Apigenina/farmacologia , Apigenina/uso terapêutico , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/farmacologia , Aspartato Aminotransferases/uso terapêutico , Glicemia , Catalase/metabolismo , Cromatografia Líquida , Diabetes Mellitus Experimental/tratamento farmacológico , Flavonoides , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Glibureto/metabolismo , Glibureto/farmacologia , Glibureto/uso terapêutico , Hemoglobinas Glicadas/metabolismo , Hidroxibenzoatos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Rim , Lactato Desidrogenases/metabolismo , Fígado , Malondialdeído/metabolismo , Estresse Oxidativo , Pâncreas , Fenóis , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ácido Quínico/farmacologia , Ratos , Estreptozocina , Espectrometria de Massas em TandemRESUMO
The rising pandemic caused by a coronavirus, resulted in a scientific quest to discover some effective treatments against its etiologic agent, the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). This research represented a significant scientific landmark and resulted in many medical advances. However, efforts to understand the viral mechanism of action and how the human body machinery is subverted during the infection are still ongoing. Herein, we contributed to this field with this compilation of the roles of both viral and human enzymes in the context of SARS-CoV-2 infection. In this sense, this overview reports that proteases are vital for the infection to take place: from SARS-CoV-2 perspective, the main protease (Mpro ) and papain-like protease (PLpro ) are highlighted; from the human body, angiotensin-converting enzyme-2, transmembrane serine protease-2, and cathepsins (CatB/L) are pointed out. In addition, the influence of the virus on other enzymes is reported as the JAK/STAT pathway and the levels of lipase, enzymes from the cholesterol metabolism pathway, amylase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and glyceraldehyde 3-phosphate dehydrogenase are also be disturbed in SARS-CoV-2 infection. Finally, this paper discusses the importance of detailed enzymatic studies for future treatments against SARS-CoV-2, and how some issues related to the syndrome treatment can create opportunities in the biotechnological market of enzymes and the development of new drugs.
Assuntos
Tratamento Farmacológico da COVID-19 , Alanina Transaminase/farmacologia , Amilases/farmacologia , Angiotensinas/farmacologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Aspartato Aminotransferases/farmacologia , Catepsinas/farmacologia , Colesterol , Corpo Humano , Humanos , Janus Quinases/farmacologia , Lactato Desidrogenases , Lipase/farmacologia , Papaína/farmacologia , SARS-CoV-2 , Fatores de Transcrição STAT/farmacologia , Serina Proteases/farmacologia , Transdução de SinaisRESUMO
Aflatoxins are potent hepatotoxic and carcinogenic secondary metabolites produced by toxigenic fungi. The present study investigated the protective effect of methanolic leaf extracts of Monanthotaxis caffra (MLEMC) against aflatoxin B1-induced toxicity in male Sprague-Dawley rats. The rats were randomly divided into 6 groups of 8 animals each. Five groups were administered orally for seven days with three different concentrations of MLEMC (100 mg/kg, 200 mg/kg and 300 mg/kg), curcumin (10 mg/kg) or vehicle (25% propylene glycol). The following day, these groups were administered 1 mg/kg b.w. of aflatoxin B1 (AFB1). The experiment was terminated three days after administration of AFB1. Group 6 represented untreated healthy control. Serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatinine and liver histopathology were evaluated. Methanolic leaf extracts of M. caffra decreased the levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and creatinine in the sera of rats as compared with the AFB1 intoxicated group. Co-administration of MLEMC improved the histological characteristics of the hepatocytes in contrast to the AFB1 treated group, which had mild to severe hepatocellular injuries including bile duct proliferation, bile duct hyperplasia, lymphoplasmacytic infiltrate and fibrosis. Extracts of M. caffra were beneficial in mitigating the hepatotoxic effects of AFB1 in rats by reducing the levels of liver enzymes and preventing hepatic injury.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Doenças dos Roedores , Aflatoxina B1/metabolismo , Aflatoxina B1/toxicidade , Alanina Transaminase/metabolismo , Alanina Transaminase/farmacologia , Animais , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/veterinária , Creatinina/metabolismo , Creatinina/farmacologia , Lactato Desidrogenases/metabolismo , Fígado , Masculino , Metanol/metabolismo , Metanol/farmacologia , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Doenças dos Roedores/metabolismo , Doenças dos Roedores/patologiaRESUMO
Investigate the effects of low-level lasers therapy (LLLT) aiming abdominal lipolysis. Female Wistar rats received applications of LLLT directly in the abdominal skin twice a week (5 weeks). Except the control group (n = 5), animals received treatments with red wavelength 660 nm being (I) R3.3 group (n = 5): 3.3 J/cm2, and (II) R5 group (n = 5): 5 J/cm2, or infrared wavelength 808 nm being (III) IR3.3 group (n = 5): 3.3 J/cm2, and (IV) IR5 group (n = 5): 5 J/cm2. Abdominal subcutaneous and liver tissues were evaluated histologically. Levels of thiobarbituric acid reactive substances (TBARS) and catalase (CAT) activity were analyzed in liver tissue. In the peripheral blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, and total cholesterol were investigated. Micronucleus assay was performed in the bone marrow. Except for the IR3.3 group, all treated groups reduced the body weight (p < 0.001). The R5 group reduced the abdominal subcutaneous tissue weight and thickness (p < 0.05), even though all treated groups reduced the number of adipocytes and its size (p < 0.001). No histological changes in the liver. There were no alterations in the triglycerides and LDL levels. The IR5 group increased the total cholesterol levels and decreased the HDL, ALT (both p < 0.05), and AST levels (p < 0.001). The group IR3.3 showed higher levels of ALP (p < 0.01). The R3.3 group increased the TBARS and CAT activity (p < 0.05). No mutagenic effects were found. The red laser treatment at 5 J/cm2 led to lipolysis and did not alter the liver's parameters.
Assuntos
Terapia com Luz de Baixa Intensidade , Animais , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/farmacologia , Feminino , Lipólise , Fígado/patologia , Terapia com Luz de Baixa Intensidade/efeitos adversos , Ratos , Ratos Wistar , Tela SubcutâneaRESUMO
Stroke is a major cause of morbidity, mortality, and disability. During ischemic stroke, a marked and prolonged rise of glutamate concentration in the brain causes neuronal cell death. This study explores the protective effect of a bioconjugate form of glutamate oxaloacetate transaminase (hrGOT), which catalyzes the depletion of blood glutamate in the bloodstream for ~6 days following a single administration. When treated with this bioconjugate, a significant reduction of the infarct volume and a better retention of sensorimotor function was observed for ischemic rats compared to those treated with saline. Moreover, the equivalent dose of native hrGOT yielded similar results to the saline treated group for some tests. Targeting the bioconjugate to the blood-brain-barrier did not improve its performance. The data suggest that the bioconjugates draw glutamate out of the brain by displacing homeostasis between the different glutamate pools of the body.
Assuntos
Encéfalo/metabolismo , Ácido Glutâmico , AVC Isquêmico , Fármacos Neuroprotetores , Animais , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/farmacologia , Barreira Hematoencefálica/metabolismo , Encéfalo/efeitos dos fármacos , Ácido Glutâmico/sangue , Ácido Glutâmico/metabolismo , AVC Isquêmico/metabolismo , AVC Isquêmico/fisiopatologia , Masculino , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologiaRESUMO
Organophosphate-induced brain damage is an irreversible neuronal injury, likely because there is no pharmacological treatment to prevent or block secondary damage processes. The presence of free glutamate (Glu) in the brain has a substantial role in the propagation and maintenance of organophosphate-induced seizures, thus contributing to the secondary brain damage. This report describes for the first time the ability of blood glutamate scavengers (BGS) oxaloacetic acid in combination with glutamate oxaloacetate transaminase to reduce the neuronal damage in an animal model of paraoxon (PO) intoxication. Our method causes a rapid decrease of blood Glu levels and creates a gradient that leads to the efflux of the excess brain Glu into the blood, thus reducing neurotoxicity. We demonstrated that BGS treatment significantly prevented the peripheral benzodiazepine receptor (PBR) density elevation, after PO exposure. Furthermore, we showed that BGS was able to rescue neurons in the piriform cortex of the treated rats. In conclusion, these results suggest that treatment with BGS has a neuroprotective effect in the PO intoxication. This is the first time that this approach is used in PO intoxication and it may be of high clinical significance for the future treatment of the secondary neurologic damage post organophosphates exposure.
Assuntos
Aspartato Aminotransferases/farmacologia , Lesões Encefálicas , Inibidores da Colinesterase/efeitos adversos , Ácido Oxaloacético/farmacologia , Paraoxon/efeitos adversos , Animais , Lesões Encefálicas/sangue , Lesões Encefálicas/induzido quimicamente , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/patologia , Proteínas de Transporte/metabolismo , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Córtex Cerebral/fisiologia , Inibidores da Colinesterase/farmacologia , Modelos Animais de Doenças , Células Hep G2 , Humanos , Masculino , Neurônios/metabolismo , Neurônios/patologia , Paraoxon/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de GABA-A/metabolismoRESUMO
Mesocestoides vogae tetrathyridia infection in mice causes hepatocyte injury, hepatic granulomatous inflammmation, liver fibrosis and chronic peritonitis manifested with portal hypertension. To reduce the detrimental effect of parasites on the host liver, the effect of the anthelmintic drug praziquantel (PZQ) in combination with natural products silymarin (an antioxidant) and beta-glucan (an immunomodulator) was investigated. The therapeutic effect of drugs was assessed by means of aminotransferase (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) activities, content of albumin, total proteins and hyaluronic acid (HA) in sera of ICR mice infected with M. vogae larvae. Animals were treated with PZQ suspended in oil emulsion (Group 1), PZQ combined with silymarin incorporated into lipid microspheres (LMS) (Group 2), PZQ combined with beta-glucan incorporated into liposomes (LG) (Group 3), PZQ co-administered with LMS and LG (Group 4). Untreated animals (Group 5) served as the control. Treatment of animals started at the early chronic phase of infection (day 14 p.i.) and lasted 10 days; serum samples were collected on days 0, 7, 14, 25, 28, 31, 35 and 45 p.i. ALT and AST activities were significantly (P < 0.05) decreased in Groups 2, 3 and 4. HA content was significantly (P < 0.05 and 0.01) lower in Groups 2 and 4. Albumin levels were decreased in Groups 2 and 4, total protein concentration decreased in Groups 1 and 3 (P < 0.05 and 0.01). These results showed that combined treatment of PZQ with silymarin and/or beta-glucan was able to ameliorate or suppress fibrogenesis in the liver, protect liver cells from oxidative damage and, possibly, stimulate regeneration of the parenchyma.
Assuntos
Infecções por Cestoides , Hipertensão Portal/tratamento farmacológico , Hepatopatias Parasitárias/tratamento farmacológico , Fígado/lesões , Mesocestoides/isolamento & purificação , Camundongos Endogâmicos ICR/parasitologia , Alanina Transaminase/farmacologia , Animais , Anti-Helmínticos/administração & dosagem , Antioxidantes/administração & dosagem , Aspartato Aminotransferases/farmacologia , Quimioterapia Combinada , Fatores Imunológicos/administração & dosagem , Fígado/parasitologia , Masculino , Mesocestoides/efeitos dos fármacos , Camundongos , Cavidade Peritoneal/parasitologia , Praziquantel/administração & dosagem , Silimarina/administração & dosagem , beta-Glucanas/administração & dosagemRESUMO
The objective of this study was to investigate the effects of 2-ME on hepatic function in exposed workers. Fifty-three impregnation workers from two copper-clad laminate-manufacturing factories using 2-ME as a solvent were recruited as the exposed group. Another group of 121 lamination workers with indirect exposure to 2-ME was recruited as the comparison group. Environmental monitoring of air 2-ME concentrations and biological monitoring of urine 2-methoxy acetic acid concentrations were performed. Venous blood was collected for blood biochemistry analyses. Liver function examination results showed that the aspartate amino transferase, alanine amino transferase, and gamma-glutamyl transferase in the 2-ME-exposed workers were not significantly different from those in the comparison workers. After adjustment for hepatitis carrier status, gender, body mass index, and duration of employment, no difference were found between exposed and comparison groups. We conclude that 2-ME was not a hepatotoxin.