RESUMO
Hepatitis A virus (HAV) infection is one of the major causes of acute hepatitis, and this infection occasionally causes acute liver failure. HAV infection is associated with HAV-contaminated food and water as well as sexual transmission among men who have sex with men. Although an HAV vaccine has been developed, outbreaks of hepatitis A and life-threatening severe HAV infections are still observed worldwide. Therefore, an improved HAV vaccine and anti-HAV drugs for severe hepatitis A should be developed. Here, we reviewed cell culture systems for HAV infection, and other issues. This review may help with improving the HAV vaccine and developing anti-HAV drugs.
Assuntos
Antivirais/farmacologia , Técnicas de Cultura de Células/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Vírus da Hepatite A/fisiologia , Hepatite A/tratamento farmacológico , Animais , Hepatite A/prevenção & controle , Hepatite A/virologia , Vírus da Hepatite A/efeitos dos fármacos , Vírus da Hepatite A/genética , Vírus da Hepatite A/imunologia , Humanos , Vacinas Virais/administração & dosagem , Vacinas Virais/genética , Vacinas Virais/imunologiaRESUMO
Microbial fermentation of plant material alters the composition of volatile and non-volatile plant natural products. We investigated the antioxidant, anticancer, and antiviral properties of extracts of defatted soybean meal fermented with Aspergillus fumigatus F-993 or A. awamori FB-133 using in vitro methods. Gas chromatography-mass spectrometry analysis of soybean meal fermented with A. awamori FB-133 and A. fumigatus F-993 identified 26 compounds with 11,14-octadecadienoic acid and methyl ester (63.63%) and 31 compounds with butylated hydroxytoluene (66.83%) and δ-myrcene (11.43%) as main constituents, respectively. The antioxidant activities of DSM extract were 3.362 ± 0.05 and 2.11 ± 0.02 mmol TE/mL, FDSM treated with A. awamori FB-133 were 4.763 ± 0.05 and 3.795 ± 0.03 mmol TE/mL and FDSM treated with A. fumigatus F-993 were 4.331 ± 0.04 and 3.971 ± 0.02 mmol TE/mL as determined by ABTS and FRAP assays, respectively. Both fermented extracts had better antioxidant activity than the unfermented extract as shown by multiple antioxidant activity assays. The concentration of fermented extracts required for 50% inhibition of cell viability was significantly lower than that of the unfermented extract when tested against the human liver cancer cell line HepG2 as shown by cell viability assays, indicating strong anticancer activity. The IC50 values for DSM, FDSM with A. fumigatusF-993 and FDSM with A. awamori FB-133 were27, 16.88 and 8.60 µg/mL, respectively. The extract of FDSM with A. awamori FB-133 showed the strongest anticancer activity, compared to DSM and FDSM with A. FumigatusF-993 extracts. Fermented extracts also reduced hepatitis A virus titres to a greater extent than unfermented extracts, thus showing strong antiviral property. Hepatitis A virus titres were reduced by 2.66 and 3 log10/0.1 mL by FDSM with A. fumigatusF-993 and FDSM by A.awamori FB-133, respectively, compared to DSM (5.50 log10/0.1 mL). Thus, the fermentation of soybean meal with A. fumigatusF-993 or A. awamori FB-133 improves the therapeutic effect of soybean extracts, which can be used in traditional medicine.
Assuntos
Antineoplásicos Fitogênicos/metabolismo , Antioxidantes/metabolismo , Antivirais/metabolismo , Fermentação , Aromatizantes/metabolismo , Glycine max/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Antivirais/farmacologia , Aspergillus fumigatus/metabolismo , Reatores Biológicos , Aromatizantes/farmacologia , Células Hep G2 , Hepatite A/tratamento farmacológico , Vírus da Hepatite A/efeitos dos fármacos , HumanosRESUMO
Hepatitis A virus (HAV) infection is a major cause of acute hepatitis including acute liver failure. Hepatitis B infection (HBV) occurs worldwide, with the highest rates in Asian and African countries, and there are several reports that HAV infection may have a more severe clinical course in patients with chronic HBV infection. We previously demonstrated that Japanese miso extracts have inhibitory effects on HAV replication. In the present study, we examined the replication of HAV and HBV in a hepatocyte superinfection model and the inhibitory effects of Japanese miso extracts on both viruses. According to the results, HAV infection inhibited HBV replication in superinfected hepatocytes, and Japanese rice-koji miso extracts had inhibitory effects on HAV replication. Our findings provide useful information for clinicians in managing HAV infection in patients with chronic HBV infection.
Assuntos
Hepatite A/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Extratos Vegetais/farmacologia , Superinfecção/tratamento farmacológico , Replicação Viral/efeitos dos fármacos , Linhagem Celular , Hepatite A/complicações , Hepatite A/virologia , Vírus da Hepatite A/efeitos dos fármacos , Vírus da Hepatite A/patogenicidade , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Hepatócitos/virologia , Humanos , Oryza/química , Extratos Vegetais/uso terapêutico , Glycine max/química , Superinfecção/complicações , Superinfecção/virologiaRESUMO
Clinacanthans nutans (Burm. f.) Lindau is a popular medicinal vegetable in Southern Asia, and its extracts have displayed significant anti-proliferative effects on cancer cells in vitro. However, the underlying mechanism for this effect has yet to be established. This study investigated the antitumor and immunomodulatory activity of C. nutans (Burm. f.) Lindau 30% ethanol extract (CN30) in vivo. CN30 was prepared and its main components were identified using high-performance liquid chromatography (HPLC) and mass spectrometry (LC/MS/MS). CN30 had a significant inhibitory effect on tumor volume and weight. Hematoxylin and eosin (H & E) staining and TUNEL assay revealed that hepatoma cells underwent significant apoptosis with CN30 treatment, while expression levels of proliferation markers PCNA and p-AKT were significantly decreased when treated with low or high doses of CN30 treatment. Western blot analysis of PAPR, caspase-3, BAX, and Bcl2 also showed that CN30 induced apoptosis in hepatoma cells. Furthermore, intracellular staining analysis showed that CN30 treatment increased the number of IFN-γ⺠T cells and decreased the number of IL-4⺠T cells. Serum IFN-γ and interleukin-2 levels also significantly improved. Our findings indicated that CN30 demonstrated antitumor properties by up-regulating the immune response, and warrants further evaluation as a potential therapeutic agent for the treatment and prevention of cancers.
Assuntos
Acanthaceae/química , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Hepatite A/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Extratos Vegetais/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/virologia , Cromatografia Líquida , Etanol/química , Etanol/isolamento & purificação , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hepatite A/imunologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/virologia , Camundongos , Estrutura Molecular , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Espectrometria de Massas em Tandem , Ensaios Antitumorais Modelo de XenoenxertoAssuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Hepatite A/tratamento farmacológico , Falência Hepática Aguda/tratamento farmacológico , Quinolonas/uso terapêutico , Febre Tifoide/tratamento farmacológico , Adulto , Antibacterianos/farmacologia , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Hepatite A/microbiologia , Humanos , Falência Hepática Aguda/microbiologia , Masculino , Testes de Sensibilidade Microbiana , Quinolonas/farmacologia , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/isolamento & purificaçãoRESUMO
Effects were studied of caleflone on the course of viral hepatitis A and B in 94 patients presenting with moderately severe form of the condition. The drug was found to have a positive effect on the course of the illness. In the patients examined, inhibitory action of caleflone on lipid peroxidation was revealed. Caleflone is recommended for use in a combined treatment of patients with viral hepatitis A and B.
Assuntos
Antivirais/uso terapêutico , Hepatite A/tratamento farmacológico , Hepatite B/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Adolescente , Adulto , Idoso , Avaliação de Medicamentos , Hepatite A/sangue , Hepatite B/sangue , Humanos , Medições Luminescentes , Pessoa de Meia-IdadeRESUMO
The therapeutic effects of prodigiozan and ibuprofen, endogenous interferon production inductors, were studied in the patients with acute viral hepatitides A and B with consideration for the body allergic reactivity at the peak of the disease. The results evidence a favourable effect of these drugs on the clinical course of the disease and on liver function; immuno- and interferon-stimulating and desensitizing effects manifested mainly in hepatitis A cases with immediate types II and III hypersensitivity and in hepatitis B cases with immediate types I and II hypersensitivity.
Assuntos
Hepatite A/imunologia , Hepatite B/imunologia , Hipersensibilidade Imediata/tratamento farmacológico , Ibuprofeno/uso terapêutico , Interferon Tipo I/deficiência , Polissacarídeos Bacterianos/uso terapêutico , Prodigiozan/uso terapêutico , Doença Aguda , Adjuvantes Imunológicos , Adolescente , Adulto , Idoso , Hepatite A/tratamento farmacológico , Hepatite B/tratamento farmacológico , Humanos , Hipersensibilidade Imediata/etiologia , Indutores de Interferon , Interferon Tipo I/biossíntese , Pessoa de Meia-IdadeRESUMO
A multiwell tissue culture system was developed to study the influence of various substances on hepatitis A virus (HAV) propagation. A panel of 20 substances of different structure types, each with known effect against at least some viruses, was studied at a concentration of 100 microM. Three substances showed reproducible inhibition. The strongest inhibitor, arabinosylcytosine, also produced cytotoxic changes in cells down to a concentration of 1 microM, and its effect was considered as nonspecific. Amantadine and ribavirin showed a moderate effect at 100 microM. A stronger inhibition was seen at 250 and 500 microM, doses that are toxic and impractical for clinical use. Although no promising candidates for antiviral treatment of hepatitis A have emerged from the present study, the assay model described here would seem useful in the screening of substances with inhibitory effects on HAV.
Assuntos
Antivirais/farmacologia , Hepatite A/tratamento farmacológico , Hepatovirus/efeitos dos fármacos , Amantadina/farmacologia , Amantadina/toxicidade , Antivirais/uso terapêutico , Antivirais/toxicidade , Linhagem Celular , Citarabina/farmacologia , Citarabina/toxicidade , Avaliação Pré-Clínica de Medicamentos , Hepatovirus/fisiologia , Humanos , Radioimunoensaio , Ribavirina/farmacologia , Ribavirina/toxicidade , Replicação Viral/efeitos dos fármacosRESUMO
The influence of interlok, biotop and remantadine on the functional activity of monocytes was determined with the use of the NBT test permitting the quantitative evaluation of this characteristic. In this study interlok was found to give promising results in the treatment of acute viral hepatitis, due both to its antiviral action and to the stimulation of the functional activity of monocytes. biotop proved to render a sharply pronounced stimulating effect on the functional activity of monocytes, thus enhancing antiviral resistance. Remantadine suppressed the functional activity of monocytes and increased their lesion by the virus, thus creating favorable conditions for virus persistence in monocytes.
Assuntos
Adamantano/análogos & derivados , Hepatite A/tratamento farmacológico , Hepatite B/tratamento farmacológico , Interferon Tipo I/uso terapêutico , Monócitos/efeitos dos fármacos , Polímeros/uso terapêutico , Rimantadina/uso terapêutico , Doença Aguda , Células Cultivadas , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Hepatite A/sangue , Hepatite B/sangue , Humanos , Monócitos/fisiologia , Nitroazul de Tetrazólio , Viremia/sangue , Viremia/tratamento farmacológicoAssuntos
Ácido 4-Aminobenzoico/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Aminobenzoatos/uso terapêutico , Hepatite A/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Proteínas do Sistema Complemento/análise , Avaliação de Medicamentos , Hepatite A/imunologia , Humanos , Imunidade Celular/efeitos dos fármacos , Imunoglobulinas/análise , Contagem de Leucócitos , para-AminobenzoatosRESUMO
The results obtained in the experimental and clinical study of the preparations of mephenamine acid and levamisole with respect to their interferonogenic and interferon-stimulating action and their therapeutic effectiveness in influenza and virus hepatitis are presented. The study has revealed that mephenamine acid, along with its capacity for stimulating the processes of interferon formation in the body, produces a pronounced curative effect, prevents the development of postinfluenza complications much more effectively than levamisole and remantadin and accelerates the processes of reparation in virus hepatitis.
Assuntos
Indutores de Interferon/uso terapêutico , Viroses/tratamento farmacológico , Adolescente , Adulto , Animais , Avaliação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Hepatite A/tratamento farmacológico , Hepatite B/tratamento farmacológico , Humanos , Influenza Humana/tratamento farmacológico , Interferons/sangue , Levamisol/uso terapêutico , Ácido Mefenâmico/uso terapêutico , Camundongos , Fatores de Tempo , Vírus da Estomatite Vesicular Indiana/efeitos dos fármacosAssuntos
Flavonoides/uso terapêutico , Hepatite A/tratamento farmacológico , S-Adenosilmetionina/uso terapêutico , Silimarina/uso terapêutico , Doença Aguda , Fatores Etários , Criança , Ensaios Enzimáticos Clínicos , Quimioterapia Combinada , Feminino , Hepatite A/diagnóstico , Humanos , Masculino , S-Adenosilmetionina/administração & dosagem , Silimarina/administração & dosagemRESUMO
In a double blind study carried out under standard conditions at two treatment centers silymarin, 2 sugar-coated tablets 70 mg three times daily, showed a definite therapeutic influence on the characteristic increased serum levels of bilirubin, GOT and GPT associated with acute viral hepatitis. The above mentioned values in 28 patients treated with silymarin were compared with those in 29 patients treated with placebo. The laboratory parameters in the silymarin group regressed more than in the placebo group after the 5th day of treatment. The number of patients having attained normal values after 3 weeks' treatment was higher in the silymarin group than in the placebo group. A statistical comparison revealed a difference between bilirubin and GOT values in the placebo and silymarin groups and a definite trend in the regression of GPT values in favour of silymarin. The course of the immune reaction in HBS Ag patients was not influenced by silymarin. As already proved by other investigators, the use of silymarin in acute viral hepatitis can lead to an accelerated regression in pathological values, thus indicating its use in the treatment of this liver disease.