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1.
Life Sci ; 273: 119235, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33607152

RESUMO

Although the central role of Nurr-1/GDNF has been reviewed amply, scarce data are available on their peripheral impact. Carvedilol and morin hydrate have previously conferred their hepatic anti-fibrotic action. AIM: Thus, our aim was to unveil the potential hepatoprotective role of carvedilol (CR) and/or morin hydrate (MH) using a hepatic 70% partial warm ischemia/reperfusion (I/R) rat model. MAIN METHOD: Rats were allocated into sham-operated, hepatic I/R, and I/R preceded by oral administration of CR (10 and 30 mg/kg; CR10/CR30), MH (30 mg/kg), or CR10 + MH for one week. KEY FINDINGS: On the molecular level, pretreatment with CR and/or MH increased the hepatic contents of Nurr-1, GDNF, and the protein expression of active/p-AKT. On the other hand, they inactivated GSK3ß and NF-κB to increase the antioxidant enzymes (GPx, SOD, CAT). All regimens also enhanced the autophagy/lysosomal function and boosted the protein expression of beclin-1, LC3II, and TFEB. Moreover, their antiapoptotic effect was signified by increasing the anti-apoptotic molecule Bcl2 and inhibiting Bax, Bax/Bcl2 ratio, and caspase-3, effects that were confirmed by the TUNEL assay. These improvements were reflected on liver function, as they decreased serum aminotransferases and liver structural alterations induced by I/R. Despite its mild impact, CR10 showed marked improvements when combined with MH; this synergistic interaction overrides the effect of either regimen alone. SIGNIFICANCE: In conclusion, CR, MH, and especially the combination regimen, conferred hepatoprotection against I/R via activating the Nurr-1/GDNF/AKT trajectory to induce autophagy/lysosomal biogenesis, inhibit GSK3ß/NF-кB hub and apoptosis, and amend redox balance.


Assuntos
Carvedilol/farmacologia , Flavonoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Isquemia/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Apoptose , Autofagia , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Isquemia/metabolismo , Isquemia/patologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
3.
Drugs R D ; 21(1): 9-27, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33336316

RESUMO

INTRODUCTION: In December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began, resulting in a number of antivirals and immune modulators being repurposed to treat the associated coronavirus disease 2019 (COVID-19). Many patients requiring treatment for COVID-19 may have either pre-existing renal or hepatic disease or experience acute renal/hepatic injury as a result of the acute infection. Altered renal or hepatic function can significantly affect drug concentrations of medications due to impaired drug metabolism and excretion, resulting in toxicity or reduced efficacy. The aim of this paper is to review the pharmacokinetics and available study data for the experimental COVID-19 therapies in patients with any degree of renal or hepatic impairment to make recommendations for dosing. METHODS: COVID-19 agents included in these recommendations were listed as primaries on the University of Liverpool COVID-19 drug interaction website ( www.covid19-druginteractions.org ), initially identified from Clinicialtrials.gov and ChicCTR.org.cn. A literature search was performed using PubMed and EMBASE as well as product licences and pharmacokinetic databases. FINDINGS: Remdesivir, dexamethasone, azithromycin, favipiravir, lopinavir/ritonavir, atazanavir, hydroxychloroquine, interferon beta, ribavirin, tocilizumab, anakinra and sarilumab were identified as experimental drugs being used in COVID-19 trials as of November 2020. Limited study data was found for these drugs in patients with renal or hepatic impairment for COVID-19 or other indications. Recommendations were made based on available data, consideration of pharmacokinetic properties (including variability), the dosing and anticipated treatment duration of each regimen in COVID-19 and known toxicities. CONCLUSION: Dosing of drugs used to treat COVID-19 in patients with renal or hepatic impairment is complex. These recommendations were produced to provide guidance to clinicians worldwide who are treating patients with COVID-19, many of whom will have some degree of acute or chronic renal or hepatic impairment.


Assuntos
Antivirais/administração & dosagem , Reposicionamento de Medicamentos/métodos , Nefropatias/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/análogos & derivados , Alanina/administração & dosagem , Alanina/análogos & derivados , /epidemiologia , Ensaios Clínicos como Assunto/métodos , Dexametasona/administração & dosagem , Relação Dose-Resposta a Droga , Humanos , Hidroxicloroquina/administração & dosagem , Nefropatias/diagnóstico , Nefropatias/epidemiologia , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia
4.
J Ethnopharmacol ; 266: 113439, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33017634

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity-induced insulin resistance and chronic inflammation appears to be the most frequent cause of diabetes and its related metabolic complications; in this way a new therapeutic approaches are needed to prevent the chronic obesity and insulin resistance. Lepidium sativum has been extensively used in traditional alternative medicine for cough, skin disease, liver disorder, diuretic, gastrointestinal problems, hair loss treatment, milk secretion during lactation as well as antioxidant, antihypertensive, anti-inflammatory, and antidiabetic activities. The hypoglycemic and hypolipidemic effect of Lepidium sativum have been observed by previous studies, but the underlying molecular mechanisms are unclear. AIM OF THE STUDY: In this study, we investigated the beneficial effect of Lepidium sativum ethanol and aqueous seed extracts on obesity, oxidative, inflammatory, and insulin sensitivity changes in the liver tissue of high fat diet (HFD)-fed rats. The bioactive constituents responsible for these activities have been identified for both extracts using HPLC and GC-MS. MATERIALS AND METHODS: Rats were fed HFD for 10 weeks. The obese rats were treated orally with the Lepidium sativum ethanol extracts (LSEE) at dose 200 and 400 mg/kg body weight (BW) and Lepidium sativum aqueous extracts (LSAE) at dose 200 mg/kg BW daily for 8 weeks. RESULTS: The findings of the present study pointed out a significant increase in the hepatic transaminases, lipid profile, leptin, and hepatic oxidative stress with decreased antioxidant capacity of HFD-fed rats. Consistent with this depiction; we determined the up-regulation of liver inflammatory markers with a significant down-regulation of insulin signaling components phospho-insulin receptor (p-IR), p-AKT, p-mammalian target of rapamycin (p-mTOR), and p-p70S6K after consumption of HFD for 10 weeks that indicates a deterioration of insulin sensitivity. Interestingly, the phytochemical screening of LSEE and LSAE exhibited positive results for phenolic, flavonoid, lipid, and some bioactive components as well as the in vitro antioxidant activity of both extracts clearly demonstrated their high antioxidant activities. Notably, LSEE and LSAE displayed a wide range of biological features including anti-obesity, anti-inflammatory, and antioxidant properties. Both extracts significantly decreased high glucose, leptin, lipid profile, liver enzymes levels, and body weight. We also found that LSEE and LSAE significantly alleviated lipid peroxidation and restored the antioxidant enzymes to normal levels. In parallel, the intracellular phosphorylation of classical markers of insulin signaling cascade p-IR/p-AKT/p-mTOR/p-p70S6K was up-regulated in the hepatic tissues of LSEE and LSAE-treated groups. CONCLUSION: This study provides evidence that LSEE and LSAE might be one promising dietary supplementation that could safely and effectively prevent the early metabolic alterations and weight gain caused by HFD further regulate the activation of insulin signaling pathway beside their powerful antioxidant and low-toxicity properties.


Assuntos
Inflamação/tratamento farmacológico , Lepidium sativum/química , Hepatopatias/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Antioxidantes/administração & dosagem , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Dieta Hiperlipídica/efeitos adversos , Relação Dose-Resposta a Droga , Inflamação/patologia , Insulina/metabolismo , Resistência à Insulina , Hepatopatias/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Sementes , Serina-Treonina Quinases TOR/metabolismo , Ganho de Peso/efeitos dos fármacos
5.
Discov Med ; 30(160): 107-112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382966

RESUMO

Liver injury has been reported as a common complication in Coronavirus disease 2019 (COVID-19). Recently, more and more studies reported that the degree of liver damages was associated with the severity of COVID-19. Although the exact mechanism of liver injury in COVID-19 patients is unknown, recent studies have made some explorations and investigations. In this review, we summarized the potential mechanisms of liver dysfunction in COVID-19 patients gleaned from recently published research reports, which suggested that the progression of pre-existing liver diseases, direct damage of liver by SARS-CoV-2, systemic inflammation caused by SARS-CoV-2 infection, anti-viral drug toxicity, and hypoxia-reperfusion may be associated with liver injury in patients with COVID-19. Hypoxic liver injury due to ischemia and shock, cholestasis-related liver injury due to altered bile metabolism, and hepatocellular injury due to drug toxicity or overwhelming inflammation might occur in severe COVID-19 patients with sepsis. To understand the pathogenesis of liver dysfunction in COVID-19 patients, further research is needed to focus on liver-related comorbidities, the evidence of viral replication in hepatocytes and bile duct cells, histological features of liver injury, and the influence of hepatotoxic antiviral drugs. We also suggested that special attention should be paid to monitoring inflammatory cytokines and hypoxia for the prevention and treatment of liver injury in severe COVID-19 patients. A deep understanding of the mechanism of liver injury is helpful for the management and treatment of COVID-19 patients.


Assuntos
/metabolismo , Hipóxia/metabolismo , Hepatopatias/metabolismo , Fígado/irrigação sanguínea , Fígado/metabolismo , /metabolismo , Antivirais/uso terapêutico , /tratamento farmacológico , Humanos , Hipóxia/tratamento farmacológico , Hipóxia/patologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Fígado/patologia , Hepatopatias/tratamento farmacológico , Hepatopatias/etiologia , Hepatopatias/patologia
6.
Life Sci ; 259: 118173, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32750437

RESUMO

The prevalence of various hepatic diseases increases dramatically worldwide and regarded as a serious health problem. Sirtuins are one of the main strategic controllers of different cellular processes, including cell cycle, mitochondrial biogenesis, insulin secretion, redox balance, inflammation, and apoptosis. SIRT1 is the most prominent and broadly studied member of sirtuins that implicated in health status and longevity. Therefore, targeting the SIRT1 signaling pathways may be a reasonable therapeutic approach to treat different diseases, including hepatic disorders. Flavonoids are polyphenolic compounds widely present in different plants and possess beneficial effects against diverse diseases. In this review, we focused on the flavonoids, (-)-epicatechin, ampelopsin, baicalin, delphinidin, fisetin, epigallocatechin-3-gallate, luteolin, pinocembrin, quercetin, silibinin, trans-chalcone and xanthohumol, to verify whether their potential promising hepatoprotective effects are related to activation of SIRT1. Additionally, molecular modeling simulations were applied to explore the potential binding mode of these flavonoids to SIRT1. The complied information and molecular docking simulations suggested that SIRT1 signaling is involved in the beneficial pharmacologic activities of flavonoids in different hepatic diseases.


Assuntos
Flavonoides/uso terapêutico , Hepatopatias/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/efeitos dos fármacos , Animais , Flavonoides/farmacologia , Humanos , Hepatopatias/fisiopatologia , Plantas/química
7.
Am J Trop Med Hyg ; 103(5): 1910-1917, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32815508

RESUMO

Liver transaminase elevations after treatment in malaria volunteer infection studies (VISs) have raised safety concerns. We investigated transaminase elevations from two human Plasmodium vivax VISs where subjects were treated with chloroquine (n = 24) or artefenomel (n = 8) and compared them with studies in Thailand (n = 41) and Malaysia (n = 76). In the VISs, alanine transaminase (ALT) increased to ≥ 2.5 × upper limit of normal (ULN) in 11/32 (34%) volunteers, peaking 5-8 days post-treatment. Transaminase elevations were asymptomatic, were not associated with elevated bilirubin, and resolved by day 42. The risk of an ALT ≥ 2.5 × ULN increased more than 4-fold (odds ratio [OR] 4.28; 95% CI: 1.26-14.59; P = 0.02) for every log10 increase in the parasite clearance burden (PCB), defined as the log-fold reduction in parasitemia 24 hours post-treatment. Although an elevated ALT ≥ 2.5 × ULN was more common after artefenomel than after chloroquine (5/8 [63%] versus 6/24 [25%]; OR 5.0; 95% CI: 0.91-27.47; P = 0.06), this risk disappeared when corrected for PCB. Peak ALT also correlated with peak C-reactive protein (R = 0.44; P = 0.012). Elevations in ALT (≥ 2.5 × ULN) were less common in malaria-endemic settings, occurring in 1/41 (2.5%) Thai patients treated with artefenomel, and in none of 76 Malaysians treated with chloroquine or artemisinin combination therapy. Post-treatment transaminase elevations are common in experimental P. vivax infection but do not appear to impact on participant safety. Although the mechanism of these changes remains uncertain, host inflammatory response to parasite clearance may be contributory.


Assuntos
Adamantano/análogos & derivados , Alanina Transaminase/sangue , Antimaláricos/uso terapêutico , Hepatopatias/tratamento farmacológico , Malária Vivax/tratamento farmacológico , Peróxidos/uso terapêutico , Plasmodium vivax/isolamento & purificação , Adamantano/uso terapêutico , Adulto , Artemisininas/uso terapêutico , Cloroquina/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Hepatopatias/sangue , Hepatopatias/parasitologia , Testes de Função Hepática , Malária Vivax/sangue , Malária Vivax/parasitologia , Malásia , Masculino , Parasitemia/tratamento farmacológico , Tailândia , Adulto Jovem
8.
Zhonghua Gan Zang Bing Za Zhi ; 28(7): 553-556, 2020 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-32791788

RESUMO

Patients with severe liver disease are prone to bacterial and fungal infections, and then develop toxic shock. The onset of the disease may be insidious, but the disease progresses rapidly with a high fatality rate. Current research results show that special conditions such as translocation of intestinal flora and immune paralysis in patients with severe liver disease are susceptible factors for infection and toxic shock. Furthermore, it is currently recognized that the treatment of severe liver disease complicated with toxic shock must be treated with antibiotics and maintenance of hemodynamic stability. Other treatments, such as hydrocortisone and strict glycemic control, are quite controversial and may not necessarily reduce mortality. Herein, we summarize the epidemiology, susceptibility factors; diagnosis and management strategies of severe liver disease complicated with toxic shock, highlighting the characteristics of toxic shock under the background of severe liver disease, so as to detect, prevent and treat septic shock in patients with severe liver disease as early as possible to reduce the fatality rate.


Assuntos
Hepatopatias , Choque Séptico , Antibacterianos/uso terapêutico , Humanos , Hepatopatias/complicações , Hepatopatias/tratamento farmacológico , Choque Séptico/complicações , Choque Séptico/tratamento farmacológico
9.
Rev Gastroenterol Mex ; 85(3): 312-320, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32620315

RESUMO

The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) virus. COVID-19 affected more than 6million persons worldwide in fewer than 4 months, after the report of the first cases in China in December 2019. The relation of the disease caused by SARS-Cov-2 to immunosuppressive treatment used in different gastrointestinal disorders is uncertain, resulting in debate with regard to suspending immunosuppressive therapy to improve infection outcome. Said suspension implies the inherent risk for graft rejection or autoimmune disease exacerbation that can potentially worsen the course of the infection. Based on the presently available evidence, a treatment stance has been established for patients with gastrointestinal diseases that require immunosuppressive therapy.


Assuntos
Infecções por Coronavirus/complicações , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Hepatopatias/tratamento farmacológico , Pancreatopatias/tratamento farmacológico , Pandemias , Pneumonia Viral/complicações , Humanos , Hepatopatias/complicações , Transplante de Fígado , Transplante de Pâncreas , Pancreatopatias/complicações
10.
Chem Biol Interact ; 327: 109187, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32610055

RESUMO

Hepatic ischemia-reperfusion injury (IRI) is not only one of the pathophysiological process involving the liver, but also a complex systemic process affecting multiple tissues and organs. IRI after liver transplant occurs due to in major resections and occlusion of vessels, or during the perioperative period, leads to acute liver failure which shows the dynamic process that involves two interrelated phases of local ischemic insult and inflammation-mediated reperfusion injury and has an impact on morbidity and mortality. The renin-angiotensin-aldosterone system (RAAS) is activated locally in the injured cells by the occurrence of I/R, which plays an essential role in the fate of the damaged tissue. However, a preclinical study explores the protective role of RAAS inhibitor in acute liver injury in a model of inflammation caused by ischemia and reperfusion. In-addition to RAAS blockers in monotherapy does not effectively block the complete pathway. Thus, the present study is designed to explore the effect of combined folic acid with RAAS blockers in combination, produce a synergistic effect. Moreover, in this review, we will describe the understanding of the possible incidence of downregulatory molecular mechanisms associated with renin-angiotensin-aldosterone system and the significance & outcome of the combination of folic acid and RAAS blockers in liver injury due to ischemia/reperfusion.


Assuntos
Ácido Fólico/uso terapêutico , Hepatopatias/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Sinergismo Farmacológico , Homocisteína/metabolismo , Humanos , Hepatopatias/fisiopatologia , Traumatismo por Reperfusão/fisiopatologia , Ácido Úrico/metabolismo
11.
Adv Exp Med Biol ; 1207: 497-528, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671772

RESUMO

Autophagy plays an important role in the physiology and pathology of the liver. It is involved in the development of many liver diseases such as α-1-antitrypsin deficiency, chronic hepatitis virus infection, alcoholic liver disease, nonalcoholic fatty liver disease, and liver cancer. Autophagy has thus become a new target for the treatment of liver diseases. How to treat liver diseases by regulating autophagy has been a hot topic.


Assuntos
Autofagia , Hepatopatias , Autofagia/efeitos dos fármacos , Hepatite Crônica , Humanos , Hepatopatias/tratamento farmacológico , Hepatopatias Alcoólicas , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Deficiência de alfa 1-Antitripsina
12.
Adv Exp Med Biol ; 1207: 689-697, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671786

RESUMO

In addition to tumors and aging that are associated with autophagy, many other diseases are also regulated by autophagy, including liver disease, myopathy, immune pathogen infection, cardiovascular disease, and so on. This chapter will detail the relationship between autophagy and these diseases and their underlying molecular mechanisms. We summarized the current research status of autophagy as a target for the treatment of related diseases, and prospected the development of related drugs and therapeutic strategies. We hope to provide new ideas for finding new therapeutic targets through the autophagic signaling pathways.


Assuntos
Autofagia/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Desenvolvimento de Medicamentos , Infecções/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Doenças Musculares/tratamento farmacológico , Humanos , Transdução de Sinais/efeitos dos fármacos
13.
BMC Infect Dis ; 20(1): 394, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493232

RESUMO

BACKGROUND: Talaromyces marneffei is a highly pathogenic fungus that can cause life-threatening fatal systemic mycosis. Disseminated Talaromycosis marneffei affects multiple organs, including the lungs, skin, and reticuloendothelial system. However, T. marneffei infection has rarely been reported in human immunodeficiency virus (HIV)-negative infants with multiple intestinal perforations and diffuse hepatic granulomatous inflammation. CASE PRESENTATION: We present the case of an HIV-negative 37-month-old boy who has had recurrent pneumonia since infancy and was infected with disseminated Talaromycosis. Contrast-enhanced computed tomography of the whole abdomen showed hepatomegaly and intestinal wall thickening in the ascending colon and cecum with mesenteric lymphadenopathy. Colonoscopy showed a cobblestone pattern with erosion, ulcer, polypoid lesions, and lumen deformation ranging from the colon to the cecum. T. marneffei was isolated from the mucous membrane of the colon, liver, and bone marrow. After antifungal treatment and surgery, his clinical symptoms significantly improved. Whole-exome sequencing using the peripheral blood of the patient and his parents' revealed a heterozygous missense mutation in exon 17 of the STAT3 gene (c.1673G>A, p.G558D). CONCLUSIONS: In T. marneffei infection-endemic areas, endoscopic examination, culture, or histopathology from the intestine tissue should be performed in disseminated Talaromycosis patients with gastrointestinal symptoms. Timely and systemic antifungal therapy could improve the prognosis. Immunodeficiency typically should be considered in HIV-negative infants with opportunistic infections.


Assuntos
Hepatopatias/diagnóstico , Micoses/diagnóstico , Fator de Transcrição STAT3/genética , Talaromyces/isolamento & purificação , Antifúngicos/uso terapêutico , Pré-Escolar , Colonoscopia , Diagnóstico Diferencial , Humanos , Mucosa Intestinal/microbiologia , Perfuração Intestinal , Hepatopatias/tratamento farmacológico , Hepatopatias/microbiologia , Masculino , Mutação de Sentido Incorreto , Micoses/tratamento farmacológico , Micoses/microbiologia , Tomografia Computadorizada por Raios X
14.
J Oleo Sci ; 69(5): 479-486, 2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32281563

RESUMO

EGCG is a major pharmacological compound in green tea. Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Inflammation and insulin resistance are involved in the development of the disease. In this study, we investigated the beneficial effect of EGCG on the liver tissue of NAFLD rats induced by a high-fat diet and its underlying mechanism. Thirty Sprague-Dawley rats received a normal diet, a HFD and a HFD+EGCG. The expression levels of inflammatory signaling pathway genes (e.g., TLR4, TRAF6, IKKß, NF-κB, TNF-α) and insulin signaling transduction pathway genes (e.g., PI3K, AKT, IRS-1, IRS-2) were detected in the liver. We observed that EGCG decreased the triglyceride (TG) concentration in rat livers and suppressed TLR4, TRAF6, IKKß, p-IKKß, p-NF-κB, and TNF-α levels compared with those in the HFD group, whereas PI3K, AKT, IRS-1, and IRS-2 indicators were improved. EGCG improves obesity-associated subacute hepatic inflammation states, probably through the TLR4 signaling pathway. Furthermore, EGCG also alleviated hepatic insulin resistance. These data indicate that EGCG improves NAFLD from two ways: inhibition of inflammation and improvement of insulin resistance in liver tissues.


Assuntos
Anti-Inflamatórios , Catequina/análogos & derivados , Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Fígado/metabolismo , Fitoterapia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Catequina/isolamento & purificação , Catequina/farmacologia , Catequina/uso terapêutico , Inflamação , Hepatopatias/etiologia , Ratos Sprague-Dawley , Chá/química
16.
Clin Gastroenterol Hepatol ; 18(7): 1561-1566, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32283325

RESUMO

BACKGROUND & AIMS: Some patients with SARS-CoV-2 infection have abnormal liver function. We aimed to clarify the features of COVID-19-related liver damage to provide references for clinical treatment. METHODS: We performed a retrospective, single-center study of 148 consecutive patients with confirmed COVID-19 (73 female, 75 male; mean age, 50 years) at the Shanghai Public Health Clinical Center from January 20 through January 31, 2020. Patient outcomes were followed until February 19, 2020. Patients were analyzed for clinical features, laboratory parameters (including liver function tests), medications, and length of hospital stay. Abnormal liver function was defined as increased levels of alanine and aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, and total bilirubin. RESULTS: Fifty-five patients (37.2%) had abnormal liver function at hospital admission; 14.5% of these patients had high fever (14.5%), compared with 4.3% of patients with normal liver function (P = .027). Patients with abnormal liver function were more likely to be male, and had higher levels of procalcitonin and C-reactive protein. There was no statistical difference between groups in medications taken before hospitalization; a significantly higher proportion of patients with abnormal liver function (57.8%) had received lopinavir/ritonavir after admission compared to patients with normal liver function (31.3%). Patients with abnormal liver function had longer mean hospital stays (15.09 ± 4.79 days) than patients with normal liver function (12.76 ± 4.14 days) (P = .021). CONCLUSIONS: More than one third of patients admitted to the hospital with SARS-CoV-2 infection have abnormal liver function, and this is associated with longer hospital stay. A significantly higher proportion of patients with abnormal liver function had received lopinavir/ritonavir after admission; these drugs should be given with caution.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Hepatopatias/epidemiologia , Hepatopatias/etiologia , Testes de Função Hepática , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Adulto , Antivirais/uso terapêutico , Bilirrubina/sangue , Análise Química do Sangue , China/epidemiologia , Enzimas/sangue , Feminino , Hospitais , Humanos , Hepatopatias/tratamento farmacológico , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pandemias , Prevalência , Estudos Retrospectivos , Ritonavir/uso terapêutico
17.
Soft Matter ; 16(11): 2725-2735, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32115597

RESUMO

Transmembrane pH gradient poly(isoprene)-block-poly(ethylene glycol) (PI-b-PEG) polymersomes were investigated for their potential use in the detoxification of ammonia, a metabolite that is excessively present in patients suffering from urea cycle disorders and advanced liver diseases, and which causes neurotoxic effects (e.g., hepatic encephalopathy). Polymers varying in PI and PEG block length were synthesized via nitroxide-mediated polymerization and screened for their ability to self-assemble into polymersomes in aqueous media. Ammonia sequestration by the polymersomes was investigated in vitro. While most vesicular systems were able to capture ammonia in simulated intestinal fluids, uptake was lost in partially dehydrated medium mimicking conditions in the colon. Polymeric crosslinking of residual olefinic bonds in the PI block increased polymersome stability, partially preserving the ammonia capture capacity in the simulated colon environment. These more stable vesicular systems hold promise for the chronic oral treatment of hyperammonemia.


Assuntos
Amônia/química , Portadores de Fármacos/química , Encefalopatia Hepática/tratamento farmacológico , Inativação Metabólica/genética , Amônia/metabolismo , Butadienos/química , Butadienos/farmacologia , Portadores de Fármacos/farmacologia , Fluoresceína-5-Isotiocianato/química , Hemiterpenos/química , Hemiterpenos/farmacologia , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Hepatopatias/complicações , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Metacrilatos/química , Tamanho da Partícula , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polimerização , Polímeros/química , Polímeros/farmacologia , Força Próton-Motriz/efeitos dos fármacos , Distúrbios Congênitos do Ciclo da Ureia/complicações , Distúrbios Congênitos do Ciclo da Ureia/tratamento farmacológico , Distúrbios Congênitos do Ciclo da Ureia/metabolismo , Água/metabolismo
18.
Int J Clin Pharmacol Ther ; 58(6): 351-353, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32194023

RESUMO

Hemocoagulase is often used for hemostasis in patients with bleeding and hemorrhagic diseases, and to avoid or stanch bleeding after surgery. Herein, three patients with hepatic diseases suffering from hypofibrinogenemia were treated with hemocoagulase agkistrodon (HCA) in Peking University People's Hospital during September 2018. All the 3 patients were chronic hepatitis B patients: Patient 1 presented with hepatic carcinoma and chronic hepatitis B, and right hepatectomy was performed; patient 2 presented with chronic hepatitis B and gastrointestinal bleeding; patient 3 presented with chronic hepatitis B, acute liver failure with hematemesis, and was awaiting liver transplantation. All three patients were percutaneously injected with HCA to prevent late-onset bleeding. After HCA was discontinued, coagulation was restored to > 60 mg/dL on day 6, without injection of fibrinogen. HCA significantly reduced the need for fibrinogen in patients with hepatic diseases, and the level of fibrinogen should be carefully monitored in clinical applications.


Assuntos
Afibrinogenemia , Agkistrodon , Batroxobina/uso terapêutico , Hemostáticos/uso terapêutico , Hepatopatias/tratamento farmacológico , Animais , Fibrinogênio , Humanos
19.
Phytomedicine ; 68: 153180, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32092638

RESUMO

BACKGROUND: Liver is the pivotal organ responsible for plasma protein production, biliary secretion, xenobiotic elimination, glucose and lipid homeostasis. Dysregulation of these functions usually leads to liver diseases and further related complications. The incidence of liver diseases is increasing worldwide, with high morbidity and mortality when at advanced stages, and has become significant public health concern and substential economic burden. Thus, novel therapeutic strategies for managing liver diseases progression are urgently required. T. ruticarpum is one of the most famous and frequently used herbal medicine and has been prescribed in traditional Chinese medicine (TCM) formulas for the treatment of various ailments, including liver diseases. A considerable amount of bioactive ingredients have been isolated and identified from the roots of T. ruticarpum, including alkaloids, saponins, phenols, volatile oils and other compounds. Among these compounds, evodiamine (EVO) and rutaecarpine (RUT) are believed to be the most bioactive compounds. PURPOSE: To summarize recent findings regarding to the metabolism, pharmacological/toxicological effects of EVO and RUT and to highlight the potential therapeutic effects of them against liver diseases. METHODS: Online academic databases (including PubMed, Google Scholar, Web of Science and CNKI) were searched using search terms of "T. ruticarpum", "Wu Zhu Yu", "evodiamine", "rutaecarpine", "liver" and combinations to include published studies of EVO and RUT primarily from 2004-2019. Several critical previous studies beyond this period were also included. RESULTS: Evodiamine (EVO) and rutaecarpine (RUT) are believed to be the most bioactive alkaloids in T. ruticarpum, having anti-inflammation, anti-fibrosis, anti-lipotoxicity, anti-cancer activities, and thus having potential to improve liver disorders. In the current review, we comprehensively summarized recent progresses in the studies of EVO- and RUT-mediated promising hepatoprotective effects and also provide novel insights regarding the potential use of EVO and RUT as therapeutic options for the treatment of liver diseases. CONCLUSION: With further in-depth pharmacology and pharmacokinetic studies, we believe that natural products in T. ruticarpum and their derivatives will become promising medicines with improved clinical efficacy for the treatment of liver diseases in the immediate future.


Assuntos
Evodia/química , Alcaloides Indólicos/farmacologia , Hepatopatias/tratamento farmacológico , Quinazolinas/farmacologia , Animais , Humanos , Alcaloides Indólicos/farmacocinética , Alcaloides Indólicos/uso terapêutico , Plantas Medicinais/química , Quinazolinas/farmacocinética , Quinazolinas/uso terapêutico
20.
Am J Trop Med Hyg ; 102(4): 832-837, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32067625

RESUMO

Hepatosplenic schistosomiasis (HSS) complicates portal hypertension, leading to life-threatening variceal bleeding. Variceal bleeding is associated with increased portal vein diameter (PVD). Beta-blockers prevent variceal bleeding. It is unclear whether beta-blockers such as propranolol can reduce PVD in HSS. We aimed to explore the effect of propranolol on PVD in HSS. A longitudinal study was conducted at the University Teaching Hospital, Zambia, as an extension of a clinical trial of rifaximin undertaken to test the hypothesis that rifaximin could reduce bacterial translocation in HSS. We randomized 85 adults to either rifaximin and standard care, or propranolol-based standard care only for 42 days. We then followed up all the patients on propranolol up to day 180. We used ultrasound to measure PVD at baseline and day 180. The primary outcome was reduction in PVD. Beta-blockade and splenic size reduction were secondary outcomes. Portal vein diameter reduced after 180 days of propranolol therapy from median 12 mm (interquartile range (IQR): 11-14) to median 10 mm (IQR: 9-13) (P < 0.001). The pulse rate reduced from baseline median 70 beats/minute (IQR: 66-80) to 65 beats/minute (IQR: 60-70) by day 180 (P = 0.006). Hemoglobin levels improved from baseline median 8 g/dL (IQR: 6-11) to 12 g/dL (10-14) (P < 0.001). Splenic size remained unchanged. Propranolol led to the reduction in PVD over 180 days. This suggests that ultrasound could be useful in monitoring response and compliance to beta-blockers, especially in resource-constraint areas where portal hypertension measurement facilities are unavailable.


Assuntos
Hipertensão Portal/etiologia , Hepatopatias/tratamento farmacológico , Hepatopatias/parasitologia , Propranolol/uso terapêutico , Esquistossomose/complicações , Adulto , Anti-Helmínticos/uso terapêutico , Antibacterianos/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Feminino , Humanos , Hipertensão Portal/tratamento farmacológico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Veia Porta , Praziquantel/uso terapêutico , Estudos Prospectivos , Rifaximina/uso terapêutico
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