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1.
Chem Pharm Bull (Tokyo) ; 72(3): 280-285, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38325836

RESUMO

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/farmacologia
2.
Acta Histochem ; 126(1): 152117, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38016413

RESUMO

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/farmacologia
3.
Pathol Res Pract ; 240: 154186, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36327814

RESUMO

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/metabolismo
4.
J Int Soc Sports Nutr ; 19(1): 623-637, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36250147

RESUMO

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 , Mioglobina
5.
Asian Pac J Cancer Prev ; 23(9): 2891-2899, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36172650

RESUMO

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 , Vitaminas
6.
Orthop Surg ; 14(9): 2286-2297, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35913384

RESUMO

OBJECTIVE: Surgical site infection is a common complication of surgery, especially in orthopedics. Povidone-Iodine (PI) is one of the oldest and most commonly used disinfectants in surgery. However, the toxicity and antimicrobial effect of PI have not been discussed. In addition, no study has explored the optimum PI concentration for sterilization and tissue healing. This study explores the germicidal efficacy of different concentrations PI, in addition, the toxicity and antibacterial effects of PI irrigation in fracture surgery are also discussed. METHODS: Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa (P. aeruginosa) were used to evaluate the germicidal efficacy of PI in vitro and in vivo. In vitro, the effects of PI on bacterial growth were analyzed. 2.5%, 1.25%, 0.5%, 0.25%, 0.05%, 0.025%, 0.005%, 0.0025% and 0% PI was added into the bacterial suspension, besides, the bacterial algebra and growth rate were tested. Meanwhile, the fluorescence intensity of viable bacteria was also tested to evaluate the effects of PI on bacterial survival. In vivo, first, femoral fracture with wound infection rat models were established. Second, thyroid gland sections, blood thyroxine, urinary iodine, wound local skin, muscle and bone tissue sections, serum creatinine and alanine aminotransferase, serum and bone local tissue interleukin-6 (IL-6), interleukin-10 (IL-10), bone morphogenetic protein (BMP-2), vascular endothelial growth factor (VEGF) and transforming growth factor (TGF-ß1) were detected in rat femoral shaft fracture model with 5%, 2.5%, 0.5%, 0.05%, and 0% PI irrigation. Third, tissue bacteria culture was tested in rat femoral fracture with wound infection model with different concentrations PI irrigation. RESULTS: In vitro, 2.5%, 1.25%, 0.5% PI inhibited the growth of bacteria. 1.25%, 0.5% PI killed all the bacteria, while 0.25%, 0.05% PI had not killed bacteria after about 10 min. The iodine absorption of 5%, 2.5%, 0.5% PI irrigation did not cause thyroid injury. The 5%, 2.5%, 0.5% PI irrigation did not make serum creatinine and alanine aminotransferase abnormal and can remove bacteria from wounds. The 0.5%, 2.5% PI irrigation can promote tissue healing and increase BMP-2, VEGF, TGF-ß1, IL-10, in addition, decrease IL-6. 5% PI irrigation would inhibit tissue healing, and increase IL-6, decrease BMP-2, VEGF, TGF-ß1, IL-10. CONCLUSIONS: Povidone-Iodine was a widely used disinfectant and 2.5%, 1.25% and 0.5% PI could effectively kill bacteria. Five percent and lower concentration PI irrigation was safe and could not cause thyroid, kidney and liver damage. The 0.5% PI irrigation was beneficial for tissue healing but 5% PI irrigation was the opposite.


Assuntos
Anti-Infecciosos Locais , Desinfetantes , Fraturas do Fêmur , Iodo , Staphylococcus aureus Resistente à Meticilina , Alanina Transaminase/farmacologia , Animais , Antibacterianos/farmacologia , Anti-Infecciosos Locais/farmacologia , Creatinina/farmacologia , Desinfetantes/farmacologia , Interleucina-10/farmacologia , Interleucina-6 , Iodo/farmacologia , Povidona-Iodo/farmacologia , Ratos , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Irrigação Terapêutica , Tiroxina , Fator de Crescimento Transformador beta1 , Fator A de Crescimento do Endotélio Vascular
7.
J Trace Elem Med Biol ; 74: 127059, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35987181

RESUMO

BACKGROUND: The aim of the present study was to assess the hazardous impact of nickel oxide nanoparticles (NiO NPs) on gills and liver of Heteropneustes fossilis. METHODS: Fishes were treated with four concentrations of NiO NPs for a period of 14 days. Nickel accumulation, lipid peroxidation, antioxidant enzymes activities (superoxide dismutase, catalase, glutathione s transferase & glutathione reductase), liver enzymes activities (aspartate amino transferase, alanine transaminase, & alkaline phosphatase), Na+/K+ ATPase activity, FTIR, metallothionein content, ethoxyresorufin-o-deethylase activity, immunohistochemistry, histology and scanning electron microscopy were analyzed in both gills and liver tissues. RESULTS: Results revealed increased accumulation of nickel in both the tissues of exposed fishes. Lipid peroxidation and activities of different antioxidant enzymes increased (except superoxide dismutase) in both the tissues after exposure. Fluctuations in liver enzymes activities and variation in the activity of Na+/K+ ATPase were also observed. FTIR data revealed shift in peaks position in both the tissues. Level of metallothionein and its expression as well as activity of ethoxyresorufin-o-deethylase and expression of CYP1A also increased in both the target tissues of treated fishes. Furthermore, histological investigation and scanning electron microscopy showed structural damages in gills as well as liver tissues of exposed fishes. CONCLUSION: Our results suggest that NiO NPs cause deteriorating effects on the gill and liver tissues of fish, therefore effluents containing these nanoparticles should be treated before their release into water bodies.


Assuntos
Peixes-Gato , Nanopartículas , Adenosina Trifosfatases , Alanina Transaminase/metabolismo , Alanina Transaminase/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Antioxidantes/metabolismo , Ácido Aspártico/metabolismo , Ácido Aspártico/farmacologia , Catalase/metabolismo , Brânquias , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos , Fígado/metabolismo , Metalotioneína/metabolismo , Níquel/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Água/farmacologia
8.
J Food Biochem ; 46(10): e14314, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35802765

RESUMO

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 Tandem
9.
Vet Med Sci ; 8(5): 2086-2091, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35838746

RESUMO

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/metabolismo
10.
Onderstepoort J Vet Res ; 89(1): e1-e6, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35384682

RESUMO

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/patologia
11.
J Feline Med Surg ; 24(6): 530-538, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34387120

RESUMO

OBJECTIVES: Phenobarbital (PB) is the most common antiseizure drug (ASD) used for the management of feline epilepsy. In dogs, PB is known to cause serum liver enzyme induction and hepatotoxicity, especially after administration long term or in high concentrations. In cats, insufficient evidence is available to draw similar conclusions. The aim of this study was to evaluate the effect of PB administration on the serum biochemistry profile of epileptic cats. As an additional objective, other adverse effects arising, related to PB treatment, were recorded. METHODS: Medical records of four veterinary centres were retrospectively reviewed for epileptic cats receiving PB treatment. Cats were included if they had a diagnosis of idiopathic epilepsy or structural epilepsy; a normal baseline serum biochemistry profile; at least one follow-up serum biochemistry profile; no concurrent disease or had not received medication that could possibly influence liver function or lead to serum liver enzyme induction. Alkaline phosphatase, alanine aminotransferase (ALT), aspartate transaminase and gamma-glutamyl transferase activities, and total bilirubin, bile acids, glucose, albumin, total protein, urea and creatinine concentrations before and during PB administration were recorded. PB serum concentration was also recorded, when available. RESULTS: Thirty-three cats (24 males, nine females) with a median age of 3 years (range 2 months to 12 years) met the inclusion criteria. Idiopathic or structural epilepsy was diagnosed in 25 (76%) and eight (24%) cats, respectively. The follow-up period ranged from 9 to 62 months. This study found an increase in ALT in three cats, possibly related to a PB serum concentration >30 µg/ml. No statistically significant increase in serum liver enzymes or other evaluated biochemistry parameters was found by comparing pre- and post-treatment parameters. CONCLUSIONS AND RELEVANCE: PB administration did not result in hepatic enzyme induction or other biochemical abnormalities in cats. This strengthens the safety profile of PB as an ASD in cats.


Assuntos
Doenças do Gato , Doenças do Cão , Epilepsia , Alanina Transaminase/farmacologia , Alanina Transaminase/uso terapêutico , Animais , Anticonvulsivantes/efeitos adversos , Doenças do Gato/induzido quimicamente , Doenças do Gato/tratamento farmacológico , Gatos , Doenças do Cão/induzido quimicamente , Doenças do Cão/tratamento farmacológico , Cães , Epilepsia/tratamento farmacológico , Epilepsia/veterinária , Feminino , Fígado , Masculino , Fenobarbital/efeitos adversos , Estudos Retrospectivos
12.
Dev Comp Immunol ; 35(1): 94-104, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20816894

RESUMO

Alanine aminotransaminase (ALT) has been identified from bacteria to plants to animals including humans. The increase in serum ALT is regarded as an index for clinical diagnosis of liver function in humans. However, ALT elevation is also reported in non-liver injury conditions and in apparently healthy people, suggesting it may play a fundamental role physiologically. Herein we isolated an alt homolog, Amphialt, from Branchiostoma japonicus, an intermediatary species from invertebrates to vertebrates, which encoded a polypeptide of 500 amino acids with more than 62 and 52% sequence identity to vertebrate and invertebrate ALT isoenzymes, respectively. It was constitutively expressed in many tissues including the hepatic caecum, the precursor of liver, and its expression in the caecum was significantly up-regulated by challenge with lipopolysaccharides (LPS). Strikingly, recombinant AmphiALT, with a specific activity of 0.114±0.02U/mg, was capable of specifically binding to the Gram-negative bacteria Escherichia coli and Aeromonas hydrophila and to their conserved molecule LPS, as well as inhibiting the growth of E. coli and causing its lysis. In contrast, AmphiALT did not bind to the Gram-positive bacteria Staphyloccocus aureus and Bacillus subtilis as well as their conserved molecule LTA. In addition, a high homology noted between amphioxus and mammalian ALT sequences suggested a functional conservation of ALT evolutionarily, hinting at the clue that mammalian ALT may also play an antibacterial role similar to that of AmphiALT. Taken together, it is proposed that AmphiALT is an immune-relevant molecule capable of identifying LPS and causing damage to Gram-negative bacteria like E. coli and A. hydrophila. It also bolsters the notion that the hepatic caecum of amphioxus is the precursor of vertebrate liver, acting as a major tissue in acute phase response.


Assuntos
Alanina Transaminase/imunologia , Alanina Transaminase/farmacologia , Antibacterianos , Bactérias/efeitos dos fármacos , Cordados/imunologia , Proteínas de Fase Aguda/química , Proteínas de Fase Aguda/imunologia , Proteínas de Fase Aguda/farmacologia , Adjuvantes Imunológicos/farmacologia , Alanina Transaminase/química , Alanina Transaminase/genética , Sequência de Aminoácidos , Animais , Antibacterianos/farmacologia , Proteínas de Transporte/química , Proteínas de Transporte/imunologia , Proteínas de Transporte/farmacologia , Regulação da Expressão Gênica , Lipopolissacarídeos/farmacologia , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/farmacologia , Microscopia Eletrônica de Varredura , Dados de Sequência Molecular , Filogenia , Proteínas Recombinantes/farmacologia , Alinhamento de Sequência
13.
J Helminthol ; 82(3): 211-9, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18394210

RESUMO

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 & dosagem
14.
Neuropharmacology ; 49 Suppl 1: 196-205, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16023153

RESUMO

Cultured mouse embryonic stem (ES) cells maintained under undifferentiated conditions (i.e. grown in medium containing 15% FCS and leukemia inhibitory factor--LIF) expressed mGlu5 metabotropic glutamate receptors. Activation of these receptors with quisqualate increased [Ca2+]i but only when cultures were deprived of extracellular glutamate, indicating that the receptor was saturated by the endogenous glutamate. Pharmacological blockade of mGlu5 receptors with 2-methyl-6-(phenylethynyl)pyridine (MPEP) or antisense-induced knock-down of mGlu5 receptors decreased the expression of the two main transcription factors that sustain ES cell self-renewal, i.e. Oct-4 and Nanog, as assessed by real-time PCR and immunoblotting. Exposure of ES cell cultures to MPEP also reduced alkaline phosphatase activity, a marker of undifferentiated ES cells. These data support a critical role for mGlu receptors in early development showing that mGlu5 receptors are expressed by ES cells and their activation sustains ES cell self-renewal in culture.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Receptores de Glutamato Metabotrópico/metabolismo , Células-Tronco/fisiologia , Alanina Transaminase/farmacologia , Animais , Northern Blotting/métodos , Western Blotting/métodos , Encéfalo/citologia , Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Células Cultivadas , Cromatografia Líquida de Alta Pressão/métodos , Interações Medicamentosas , Embrião de Mamíferos , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios , Citometria de Fluxo/métodos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Ácido Glutâmico/análise , Interleucina-6/farmacologia , Fator Inibidor de Leucemia , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oligodesoxirribonucleotídeos Antissenso/farmacologia , Piridinas/farmacologia , Ácido Quisquálico/farmacologia , RNA Mensageiro/biossíntese , Receptor de Glutamato Metabotrópico 5 , Receptores de Glutamato Metabotrópico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Células-Tronco/efeitos dos fármacos , Timidina/metabolismo , Fatores de Tempo , Trítio/metabolismo
15.
Food Chem Toxicol ; 40(4): 545-9, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11893413

RESUMO

The effects of betaine or taurine on hepatotoxicity induced by lipopolysaccharide (LPS) were examined in adult male SD rats. Rats were provided with drinking water containing either 1% betaine or taurine for 2 weeks prior to challenge with LPS (5 mg/kg, iv). Supplementation with betaine or taurine protected the animals from induction of LPS hepatotoxicity as measured by changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities and total bilirubin levels in serum, and hepatic glutathione contents. LPS challenge increased serum TNF-alpha and nitrate/nitrite in rats, which were reduced by betaine or taurine intake. Taurine depletion induced by supply of drinking water containing 3% beta-alanine for 7 days did not enhance the LPS-induced hepatic damage or the decrease in hepatic glutathione level. The results indicate that intake of betaine or taurine attenuates the LPS-induced hepatotoxicity resulting from activation of Kupffer cells.


Assuntos
Betaína/farmacologia , Fármacos Gastrointestinais/farmacologia , Lipopolissacarídeos/toxicidade , Fígado/patologia , Taurina/farmacologia , Administração Oral , Alanina Transaminase/farmacologia , Animais , Aspartato Aminotransferases/farmacologia , Bilirrubina/sangue , Células de Kupffer , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Ratos , Ratos Sprague-Dawley
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