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1.
Zhongguo Zhong Yao Za Zhi ; 45(19): 4746-4755, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33164442

RESUMO

To systematically evaluate the efficacy and safety of Chinese medicine in the treatment of drug-induced liver injury(DILI). By searching the randomized controlled trials(RCTs) of the Chinese medicine published in CNKI, WanFang, VIP, PubMed, Web of Science, in a time limit from database establishment to May 1, 2020. The bias risk assessment and Meta-analysis were then conducted for the included studies. Seventeen studies were finally included, all of which were RCTs, including 1 407 patients. The experimental group was treated with Chinese herbal medicine decoction or Chinese patent medicine, involving a total of 11 kinds of drugs, and the control group was treated with conventional Western medicine. Meta-analysis results showed that, in terms of treatment effective rate, Yinlan Yigan Granules, Shuganning, Jiangmeiling Capsules, Baidan Shugan Recipe and Sini Shugan Decoction were all superior to Western medicine treatment. In terms of reducing alanine aminotransferase(ALT), Yinlan Yigan Granules, Shuganning, Hugan Jiedu Recipe, Wuzhi Tablets, Wucao Baogan Recipe and Liuwei Wuling Tablets were superior to Western medicine. In terms of reducing aspartate aminotransferase(AST), Shuganning, Hugan Jiedu Recipe, Wucao Baogan Recipe, Liuwei Wuling Tablets and Sini Shugan Decoction were all superior to Western medicine. In terms of reducing total bilirubin(TBiL), Yinlan Yigan Granules, Shuganning, Jiedu Hugan Yin, Wuzhi Tablets, Wucao Baogan Recipe, Baidan Shugan Recipe and Sini Shugan Decoction were all superior to Western medicine treatment. Combined with network Meta-analysis and probability ranking, it can be seen that, Jiangmeiling Capsules, Shuganning, Sini Shugan Decoction and Baidan Shugan Recipe were most likely to be the best drugs to improve the efficiency and reduce ALT, AST, TBiL, respectively, with certain advantages compared to conventional Western medicine treatment. Of the seventeen studies included, eight studies described safety issues, three of which involved the test group, all of which were minor adverse reactions that disappeared after drug withdrawal or symptomatic treatment. However, due to the low quality of the included studies, more high-quality clinical studies are needed for further verification, thus providing more evidence-based medical evidence for Chinese medicine intervention in DILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Medicina Tradicional Chinesa , Metanálise em Rede , Medicamentos sem Prescrição , Resultado do Tratamento
2.
Environ Health Prev Med ; 25(1): 53, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917140

RESUMO

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


Assuntos
Tetracloreto de Carbono/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fibrose/tratamento farmacológico , Inflamação/tratamento farmacológico , Substâncias Protetoras/farmacologia , Urticaceae/química , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fibrose/genética , Inflamação/genética , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
3.
Ann Agric Environ Med ; 27(3): 368-373, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32955216

RESUMO

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


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Clorpirifos/toxicidade , Hidrogênio/farmacologia , Inseticidas/toxicidade , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Relação Dose-Resposta a Droga , Masculino , Estresse Oxidativo/genética , Ratos , Ratos Wistar
4.
Life Sci ; 259: 118382, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32898532

RESUMO

AIM: Vancomycin (VCM) is a glycopeptide antibiotic widely used to treat serious infections caused by methicillin-resistant Staphylococcus aureus and has been associated with some severe side effects such as hepatotoxicity and nephrotoxicity. However, the underlying mechanism of VCM-induced hepatotoxicity is not yet fully understood. Therefore, the current study was designed to evaluate the protective effects of zingerone (Zin) against VCM-induced hepatotoxicity in rats. MATERIALS AND METHODS: VCM was intraperitoneally administered at a dose of 200 mg/kg body weight (b.w.) for 7 days alone and in combination with the orally administered Zin (25 and 50 mg/kg b.w). KEY FINDINGS: Zin treatment significantly improved VCM-induced hepatic lipid peroxidation, glutathione depletion, reduced antioxidant enzyme (superoxide dismutase, catalase and glutathione peroxidase) activities and liver function markers (aspartate aminotransferase, alkaline phosphatase and alanine aminotransferase). Histopathological integrity and immunohistochemical expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the VCM-induced liver tissue were ameliorated after Zin administration. In addition, Zin reversed the changes in levels and/or activities of inflammatory and apoptotic parameters such as nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), p53, cysteine aspartate specific protease-3 (caspase-3), cysteine aspartate specific protease-8 (caspase-8), cytochrome c, Bcl-2 associated X protein (Bax) and B-cell lymphoma-2 (Bcl-2) in the VCM-induced hepatotoxicity. SIGNIFICANCE: Collectively, these results reveal probable ameliorative role of Zin against VCM-induced hepatotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Guaiacol/análogos & derivados , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Vancomicina/toxicidade , Animais , Western Blotting , Ciclo-Oxigenase 2/metabolismo , Guaiacol/uso terapêutico , Interleucina-1beta/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
5.
J Oleo Sci ; 69(9): 1107-1115, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879198

RESUMO

Medicinal plants and their secondary metabolites have long been a rich source of biologically active compounds that can prevent many diseases. In this context, we investigated the antioxidant activities of the essential oil of Lavandula officinalis and tested its potency against hepatic and renal toxicity induced by hydrogen peroxide in adult male mice based on measurements of biochemical parameters, oxidative stress, and tissue damage in both organs. We proved a remarkable antioxidant power of this plant (in vitro) by correcting the harmful effects of the prooxidant (in vivo). It can be concluded that lavender is an aromatic plant capable of reducing the stress caused by reactive oxygen species.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/tratamento farmacológico , Antioxidantes , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Peróxido de Hidrogênio/toxicidade , Lavandula/química , Óleos Voláteis/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Folhas de Planta/química , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Feminino , Técnicas In Vitro , Masculino , Camundongos , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
6.
Chem Biol Interact ; 330: 109230, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32828744

RESUMO

Although physiological levels of iron are essential for numerous biological processes, excess iron causes critical tissue injury. Under iron overload conditions, non-chelated iron generates reactive oxygen species that mediate iron-induced tissue injury with subsequent induction of apoptosis, necrosis, and inflammatory responses. Because liver is a central player in iron metabolism and storage, it is vulnerable to iron-induced tissue injury. Taxifolin is naturally occurring compound that has shown potent antioxidant and potential iron chelation competency. The aim of the current study was to investigate the potential protective effects of taxifolin against iron-induced hepatocellular injury and to elucidate the underlining mechanisms using rats as a mammalian model. The results of the current work indicated that taxifolin inhibited iron-induced apoptosis and enhanced hepatocellular survival as demonstrated by decreased activity of caspase-3 and activation of the pro-survival signaling PI3K/AKT, respectively. Western blotting analysis revealed that taxifolin enhanced liver regeneration as indicated by increased PCNA protein abundance. Taxifolin mitigated the iron-induced histopathological aberration and reduced serum activity of liver enzymes (ALT and AST), highlighting enhanced liver cell integrity. Mechanistically, taxifolin modulated the redox-sensitive MAPK signaling (p38/c-Fos) and improved redox status of the liver tissues as indicated by decreased lipid peroxidation and protein oxidation along with enhanced total antioxidant capacity. Interestingly, it decreased liver iron content and down-regulated the pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß. Collectively, these data highlight, for the first time, the ameliorating effects of taxifolin against iron overload-induced hepatocellular injury that is potentially mediated through anti-inflammatory, antioxidant, and potential iron chelation activities.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Sobrecarga de Ferro/complicações , Regeneração Hepática/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Quercetina/análogos & derivados , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Ferro/metabolismo , Quelantes de Ferro/farmacologia , Quelantes de Ferro/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos
7.
Chem Biol Interact ; 329: 109213, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32739323

RESUMO

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


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Isoflavonas/metabolismo , Substâncias Protetoras/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Inflamação/prevenção & controle , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Cirrose Hepática/metabolismo , Cirrose Hepática/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia
8.
Am J Chin Med ; 48(5): 1141-1157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32668974

RESUMO

Oxidative stress is considered as a major factor in aging and exacerbates aging process through a variety of molecular mechanisms. D-galactose, a normal reducing sugar with high dose can cause the accumulation of reactive oxygen species (ROS) or stimulate free radical production indirectly by the formation of advanced glycation end products in tissues, finally resulting in oxidative stress. 20(R)-ginsenoside Rg3 (20(R)-Rg3), a major and representative component isolated from red ginseng (Panax ginseng C.A Meyer), has been shown to observably have an anti-oxidative effect. We thereby investigated the beneficial effects of 20(R)-Rg3 on D-galactose-induced oxidative stress injury and its underlying mechanisms. Our results showed that continuous injection of D-galactose with 800[Formula: see text]mg/kg/day for 8 weeks increased the levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN). However, such increases were attenuated by the treatment of 20(R)-Rg3 for 4 weeks. Meanwhile, 20(R)-Rg3 markedly inhibited D-galactose-caused oxidative stress in liver and kidney. The anti-oxidants, including catalase (CAT) and superoxide dismutase (SOD), were elevated in the mice from 20(R)-Rg3-treated group compared with that from D-galactose group. In contrast, a significant decrease in levels of cytochrome P450 E1 (CYP2E1) and the lipid peroxidation product malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were observed in the 20(R)-Rg3-treated group. These effects were associated with a significant increase of AGEs. More importantly, 20(R)-Rg3 effectively attenuated D-galactose induced apoptosis in liver and kidney via restoring the upstream PI3K/AKT signaling pathway. Taken together, our study suggests that 20(R)-Rg3 may be a novel and promising anti-oxidative therapeutic agent to prevent aging-related injuries in liver and kidney.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Galactose/efeitos adversos , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Panax/química , Fitoterapia , Animais , Antioxidantes , Modelos Animais de Doenças , Ginsenosídeos/isolamento & purificação , Produtos Finais de Glicação Avançada/metabolismo , Camundongos Endogâmicos ICR , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
9.
Int. j. morphol ; 38(3): 558-564, June 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1098287

RESUMO

Chronic hepatotoxicity is a debilitating and frequently life-threatening disease resulting in progressive liver failure. The toxic chemical, thioacetamide (TAA) is used to evaluate hepatoprotective agents, and the polyphenolic compound, resveratrol was proposed as a novel treatment for diseases with hyperactivation of the mammalian target of rapamycin (mTOR) cell signaling pathway. This analysis sought to investigate the potential protective effect of resveratrol against liver injury induced by TAA via the inhibition of hepatic mTOR. Model group rats received several injections of TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed at week 10 and the protective group was pretreated with resveratrol (20 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment. Harvested liver tissues were examined using light microscopy and liver homogenates were assayed for biomarkers of inflammation and assessed the levels of mTOR protein in all animal groups. In addition, blood samples were assayed for biomarkers of liver injury enzyme. TAA substantially damaged the hepatic tissue of the model group such as infiltration of inflammatory cells, vacuolated cytoplasm, dark pyknotic nuclei, and dilated congested blood vessel that were effectively protected by resveratrol. Resveratrol also significantly (p<0.05) inhibited TAA-induced mTOR, high sensitivity c-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in harvested liver homogenates and blood samples. Thus, we conclude that resveratrol effectively protects against TAA-induced hepatotoxicity in rats, possibly due to the inhibition of mTOR and inflammation.


La hepatotoxicidad crónica es una enfermedad debilitante y potencialmente mortal que produce insuficiencia hepática progresiva. La toxicidad del químico de la tioacetamida (TAA) se utiliza para evaluar los agentes hepatoprotectores y el compuesto polifenólico, resveratrol, se propuso como un nuevo tratamiento para enfermedades con hiperactivación de la vía de señalización celular mTOR (mammalian Target of Rapamycin). Aquí buscamos investigar el posible efecto protector del resveratrol contra la lesión hepática inducida por TAA a través de la inhibición de la vía de señalización mTOR en hepatocitos. Las ratas del grupo modelo recibieron varias inyecciones de TAA (200 mg / kg; dos veces por semana durante 8 semanas) antes de ser sacrificadas en la semana 10 y el grupo protector se trató previamente con resveratrol (20 mg / kg) diariamente durante dos semanas antes de las inyecciones de TAA y continuó recibiendo ambos agentes hasta el final del experimento. Se examinaron los tejidos hepáticos recolectados usando microscopía óptica y se analizaron los homogeneizados hepáticos para detectar biomarcadores de inflamación y se evaluaron los niveles de proteína mTOR en todos los grupos de animales. Además, se analizaron muestras de sangre para detectar biomarcadores de la enzima de lesión hepática. TAA dañó sustancialmente el tejido hepático del grupo modelo, con infiltración de células inflamatorias, citoplasma vacuolado, núcleos picnóticos oscuros y vasos sanguíneos congestionados dilatados que estaban efectivamente protegidos por el resveratrol. El resveratrol también inhibió significativamente (p <0.05) mTOR, proteína C-reactiva (hs-CRP), factor de necrosis tumoral alfa (TNF-α), interleucina-6 (IL-6), alanina aminotransferasa (ALT ) y aspartato aminotransferasa (AST) en las muestras de sangre y de hígados recolectados. En conclusión, el resveratrol protege eficazmente contra la hepatotoxicidad inducida por TAA en ratas, posiblemente debido a la inhibición de mTOR y de la inflamación.


Assuntos
Animais , Masculino , Camundongos , Tioacetamida/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Resveratrol/administração & dosagem , Aspartato Aminotransferases/análise , Proteína C-Reativa/análise , Fator de Necrose Tumoral alfa/análise , Alanina Transaminase/análise , Modelos Animais de Doenças
10.
J Nat Med ; 74(4): 788-795, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32533386

RESUMO

Soshiho-tang (SSHT) has traditionally been used to treat gastrointestinal disorders. In this experiment, we investigated the protective effect of SSHT on inflammatory liver injury in lipopolysaccharide (LPS)-sensitized mice. Male C57BL/6J mice aged 6 weeks were randomly placed in 6 groups (n = 5): normal mice (CTR), LPS-sensitized mice (LPS), LPS-sensitized mice treated with dexamethasone (DEX) and LPS-sensitized mice treated with 0.05, 0.55, and 5.55 g/kg of SSHT (SSHT 0.05, SSHT 0.55, and SSHT 5.55). Various doses of SSHT was given once a day for 7 days. After 2 h of LPS injection, the liver tissue was collected. SSHT pretreatment recovered hemorrhage of liver tissues in LPS-induced acute liver injury. The expressions of MAP Kinase, NF-κB, IκBα, p-IκBα, COX-2, and iNOS protein levels were markedly decreased by SSHT-treated liver tissues. Additionally, SSHT pretreatment significantly regulated the expressions of MCP-1, TNF-α, and IL-6 cytokines. These results suggest the potential of SSHT on the protection of acute liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Inflamação/tratamento farmacológico , Lipopolissacarídeos/efeitos adversos , Fígado/patologia , Extratos Vegetais/química , Doença Aguda , Animais , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
12.
Food Chem ; 328: 127135, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32473490

RESUMO

Watermelon seed, a watermelon processing industry by-product, is a good protein source for the preparation of antioxidant peptides due to its high protein content, low cost, special amino acid composition. Antioxidant hydrolysates obtained from watermelon seed protein (WSP) after slit divergent ultrasound (SDU) treatment were studied. The stepwise multiple linear regression model verified that the reducing power of watermelon seed protein hydrolysates (WSPHs) is positively related with -SH and ß-turn content of WSP (R2 = 0.931, p < 0.01). Using the degree of hydrolysis (DH) and reducing power as indicators, the WSPHs was prepared under the optimal conditions (ultrasound frequency: 20/28 kHz, time: 60 min, power density: 100 W/L) and divided into three components by ultrafiltration membrane (1 and 5 kDa). Compared with WSPHs and other fractions, WSPHs-I (Mw < 1 kDa) not only significantly protected HepG2 cells from H2O2-induced damage, but also greatly alleviated the liver injury caused by d-galactose in male SD rats.


Assuntos
Antioxidantes/farmacologia , Citrullus/química , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacologia , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Enzimas/metabolismo , Galactose/toxicidade , Células Hep G2 , Humanos , Peróxido de Hidrogênio/farmacologia , Hidrólise , Modelos Lineares , Masculino , Proteínas de Plantas/química , Proteínas de Plantas/farmacologia , Ratos Sprague-Dawley , Sementes/química , Ultrassom/instrumentação , Ultrassom/métodos
13.
J Ayub Med Coll Abbottabad ; 32(1): 28-32, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32468750

RESUMO

BACKGROUND: Autonomic nervous system modulates acetaminophen induced hepatotoxicity. The purpose of the study was to determine the hepatoprotective effect of α1 antagonist (prazosin) and ß2 agonist (salbutamol) on acetaminophen induced hepatotoxicity in mice. METHODS: This experimental study was conducted at Post Graduate Medical Institute, Lahore in which 50 adult mice were divided in to five groups. With the exception of normal control, hepatotoxicity was induced in all other study groups by giving single intraperitoneal injection of acetaminophen 300 mg/ kg. First and second groups served as normal and toxic control were given distilled water 6 ml/ kg while third, fourth and fifth experimental groups were given N-acetylcysteine (300 mg/ kg), prazosin (0.18 mg/ kg) and salbutamol (0.35 mg/kg) intraperitoneally at 2,4 and 8 hours after acetaminophen injection. Serum liver enzymes were analysed at 0 and 72 hours while histopathological finding were assessed at the end of study by using SPSS-20. RESULTS: All the groups treated with toxic dose of acetaminophen showed significant increase in serum ALT, i.e., B (Toxic control 3372%), C (NAC treated 282%), D (Prazosin treated 582%), E(Salbutamol treated 3297%) and AST levels, i.e., B (Toxic control 2750% ), C (NAC treated 230% ), D (Prazosin treated 280%), E (Salbutamol treated 828%) with p-value ˂0.001. When this increase was compared between groups, the lowest increase in serum ALT and AST levels was observed in Nacetylcysteine and prazosin group with no significant difference. Similarly, experimental animals receiving prazosin and N-acetylcysteine had the lowest inflammation, degeneration and necrosis scores than the toxic control group in histopathological analysis of the liver with p-value <0.001. CONCLUSIONS: The hepatoprotective effect of prazosin is comparable to N- acetylcysteine against acetaminophen induced hepatotoxicity in mice.


Assuntos
Acetaminofen/efeitos adversos , Acetilcisteína/uso terapêutico , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Depuradores de Radicais Livres/uso terapêutico , Prazosina/uso terapêutico , Albuterol/uso terapêutico , Analgésicos não Entorpecentes/efeitos adversos , Animais , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Feminino , Fígado/patologia , Masculino , Camundongos , Necrose
14.
Biomed Environ Sci ; 33(4): 238-247, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32438961

RESUMO

Objective: This study aimed to explore the protective effect of procyanidin B2 (PCB2) on acute liver injury induced by aflatoxin B 1 (AFB 1) in rats. Methods: Forty Sprague Dawley rats were randomly divided into control, AFB 1, AFB 1 + PCB2, and PCB2 groups. The latter two groups were administrated PCB2 intragastrically (30 mg/kg body weight) for 7 d, whereas the control and AFB 1 groups were given the same dose of double distilled water intragastrically. On the sixth day of treatment, the AFB 1 and AFB 1 + PCB2 groups were intraperitoneally injected with AFB 1 (2 mg/kg). The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide (DMSO). On the eighth day, all rats were euthanized: serum and liver tissue were isolated for further examination. Hepatic histological features were assessed by hematoxylin and eosin-stained sections. Weight, organ coefficient (liver, spleen, and kidney), liver function (serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin), oxidative index (catalase, glutathione, superoxide dismutase, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine), inflammation factor [hepatic interleukin-6 (IL-6) mRNA expression and serum IL-6], and bcl-2/bax ratio were measured. Results: AFB 1 significantly caused hepatic histopathological damage, abnormal liver function, oxidative stress, inflammation, and bcl-2/bax ratio reduction compared with DMSO-treated controls. Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB 1. Conclusion: Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB 1.


Assuntos
Aflatoxina B1/toxicidade , Biflavonoides/farmacologia , Catequina/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Venenos/toxicidade , Proantocianidinas/farmacologia , Substâncias Protetoras/farmacologia , Animais , Biflavonoides/administração & dosagem , Catequina/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Masculino , Proantocianidinas/administração & dosagem , Substâncias Protetoras/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
15.
Acta Cir Bras ; 35(2): e202000204, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294688

RESUMO

PURPOSE: To investigate the effect of growth arrest-specific protein 6 (Gas6) on acute liver injury in mice and related mechanisms. METHODS: Thirty C57BL/6 (6-8 weeks old) mice were randomly divided into control, LPS/D-GalN, and LPS/D-GalN+Gas6 groups (10 mice in each group). The LPS/D-GalN group was intraperitoneally administered with LPS (0.25 mg/Kg) and D-GalN (400 mg/Kg) for 5h. The LPS/D-GalN+Gas6 group was intraperitoneally administered with rmGas6 one hour before intraperitoneal application of LPS/D-GalN. All subjects were sacrificed at 5 h for blood and tissue analysis. The expression of protein and mRNA was assessed by western blotting and RT-PCR, respectively. RESULTS: Compared with the control group, AST, ALT, IL-1ß, TNF-α, IL-6 IL-10, MPO activity were increased in the LPS/D-GalN group. However, they were significantly inhibited by Gas6. Gas6 markedly suppressed the expression of apoptosis-related protein induced by LPS/D-GalN. Moreover, Gas6 attenuated the activation of the NF-κB signaling pathway in acute liver injury induced by LPS/D-GalN. CONCLUSIONS: Gas6 alleviates acute liver injury in mice through regulating NF-κB signaling pathways. Gas6 can be a potential therapeutic agent in treating LPS/D-GalN-induced acute liver injury in the future.


Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Lipopolissacarídeos/efeitos adversos , Fígado/efeitos dos fármacos , Animais , Anti-Inflamatórios/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Masculino , Camundongos
16.
Chin J Nat Med ; 18(3): 211-218, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32245591

RESUMO

Cholestasis is caused by the obstacle of bile formation or secretion and can develop into severe liver diseases. We previously reported the ethanol extract of Schisandra sphenanthera (Wuzhi tablet, WZ) can significantly protect against lithocholic acid (LCA)-induced intrahepatic cholestasis in mice, partially due to the activation of PXR pathway and promotion of liver regeneration. However, the effect of WZ on the bile acids profile and gut microbiome in cholestastic mice remain unknown. In this study, the effect of WZ against LCA-induced liver injury was evaluated and its effect on the bile acids metabolome and gut microbiome profiles in cholestastic mice was further investigated. Targeted metabolomics analysis was performed to examine the change of bile acids in the serum, liver, intestine and feces. The change of intestinal flora were detected by the genomics method. Targeted metabolomics analysis revealed that WZ enhanced the excretion of bile acids from serum and liver to intestine and feces. Genomics analysis of gut microbiome showed that WZ can reverse LCA-induced gut microbiome disorder to the normal level. In conclusion, WZ protects against LCA-induced cholestastic liver injury by reversing abnormal bile acids profiles and alteration of gut microbiome.


Assuntos
Ácidos e Sais Biliares/metabolismo , Colestase/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal , Extratos Vegetais/farmacologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Colestase/induzido quimicamente , Ácido Litocólico , Masculino , Metaboloma , Camundongos , Camundongos Endogâmicos C57BL , Schisandra/química , Comprimidos
17.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1399-1405, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32281354

RESUMO

This study aimed to investigate the protective effect of water extracts of Orychophragmus violaceus seeds on liver injury induced by thioacetamide(TAA) in mice. ICR male mice were randomly divided into seven groups: normal group, model group, bicyclol positive control group(200 mg·kg~(-1)), Kuihua Hugan Tablets group(350 mg·kg~(-1)), O. violaceus seeds low-dose water extract group(125 mg·kg~(-1)), middle-dose water extract group(250 mg·kg~(-1)), and high-dose water extract group(500 mg·kg~(-1)). Intragastric administration was given in all groups at 0.02 mL·g~(-1) body weight, 1 time a day for continuous 4 days. One h after the administration on the 4 th day, the liver injury model was induced by intraperitoneal injection of TAA(100 mg·kg~(-1)). The mice were put to death 24 hours later. Blood and tissues were taken and organ indexes were calculated. The activities of ALT, AST and TBiL in serum were detected. The content of MDA, GSH and the activity of SOD, GSH-Px in liver homogenate were examined by colorimetry method. HE staining was used to observe the pathological changes of liver tissues in mice. The protein expression levels of NF-κB p65, Keap-1, Nrf2, p-p38, p-JNK, p-ERK, Bax, Bcl-2, caspase-3, cleaved caspase-3 and caspase-8 were detected by Western blot. The results showed that as compared with the model group, various O. violaceus seeds groups could significantly improve the pathological conditions of liver and reduce ALT, AST, TBiL activities in serum of mice with liver injury. In the high-dose group, the activities of SOD, GSH-Px and the content of GSH were significantly increased, while MDA content was sharply declined. Meanwhile, O. violaceus seeds extract down-regulated the expressions of Bax, Keap-1, p-p38, p-JNK, p-ERK, NF-κB p65, cleaved caspase-3 and up-regulated the expressions of Nrf2, Bcl-2, caspase-3 and caspase-8. In conclusion, O. violaceus seeds extract exhibited potent protective effect on liver injury induced by TAA in mice, and its mechanism may be related to down-regulating levels of Keap-1, up-regulating the expressions of Nrf2, inhibiting the expressions of p-p38, p-ERK and NF-κB p65 signaling pathway, and inhibiting hepatocyte apoptosis by down-regulating the expressions of p-JNK and Bax and up-regulating the expressions of Bcl-2.


Assuntos
Brassicaceae/química , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Extratos Vegetais/farmacologia , Sementes/química , Animais , Apoptose , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo , Transdução de Sinais , Tioacetamida
18.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1433-1439, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32281358

RESUMO

The aim of this study was to observe the protective effect of water extract from Sabia parviflora on mice with acute liver injury induced by acetaminophen, and investigate its possible mechanism. Fifty-eight Kunming mice were divided into 6 groups, 8 in the normal group, 10 in the model group, 10 in the biphenyl diester group, and 10 each in the low, medium and high dose groups. After adaptive feeding for one week, the mice in normal group were intragastrically administered with an equal volume of 0.5% sodium carboxymethylcellulose sodium(CMC-Na), and the mice in other groups were intragastrically administered with corresponding drugs at 20 mL·kg~(-1) once a day. Then acetaminophen(200 mg·kg~(-1)) was administered after the above drug administration except the normal group. The behavior and signs of the experimental animals were observed every day and the samples were taken for experiments on the next day of the final administration. The liver mass and mass index were calculated. The blood was collected from the abdominal aorta and centrifuged to obtain the serum for detecting aspartate aminotransferase(AST) activity and alanine aminotransferase(ALT) activity. The liver tissue homogenate was used to detect superoxide dismutase(SOD) activity, glutathione(glutathione, r-glutamyl cysteingl+glycine, GSH) activity and malondialdehyde(MDA) content. Liver tissue was analyzed for histological analysis. The results showed that S. parviflora could alleviate the lipid peroxidation damage in the liver caused by acetaminophen, reduce the ALT and AST activities in serum, increase the levels of SOD and GSH in liver tissue, decrease the content of MDA in liver tissue, and inhibit the apoptosis. S. parviflora could also improve the live histopathological profile, protect liver cells and restore liver function. Among them, the high dose had the most significant effect and showed dose-effect relationship. This study indicated that S. parviflora had a significant protective effect on acetaminophen-induced liver injury in mice, and its mechanism may be related to its anti-oxidation effect and inhi-bitory effect on apoptosis.


Assuntos
Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Fígado/enzimologia , Malondialdeído/análise , Camundongos , Estresse Oxidativo , Superóxido Dismutase/metabolismo
19.
BMC Complement Med Ther ; 20(1): 115, 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32307011

RESUMO

BACKGROUND: In the present study, the poncirin which is flavonoid-7-o-glycosides (isolated from the Poncirus trifoliata) in nature was evaluated against the Carbon tetra chloride (CCL4)-induced liver injury. The poncirin have been reported for various anti-inflammatory, analgesic activity etc. Based on the previous studies it was anticipated that the poncirin will ameliorate CCL4-induced liver injury. METHODS: The CCL4-induced acute and chronic liver injury model (albino BALB/c mice) was used. Following the induction of the liver injury various parameters such as food and water intake, body weight and weight to dry ratio changes were assessed. Furthermore, various hematological, biochemical parameters and histological studies such as hemotoxylin and eosin (H and E) staining were performed. The poncirin treatment was also evaluated against the pro-inflammatory cytokines such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) using enzyme link immunosorbant assay (ELISA). The Swiss Target prediction software was used to investigate interaction of the poncirin on the various hepatic enzymes. RESULTS: The poncirin treatment markedly improved the behavioral parameters such as food and water intake. The liver weight variation was attenuated and total body was improved markedly. The hematological and biochemical parameters were significantly improved compared to the CCL4 treated groups. The anti-oxidants were induced, while oxidative stress markers were reduced promisingly. The H and E staining showed that poncirin treatment significantly improved the histology of liver compared to the CCL4 treated group. Furthermore, the poncirin treatment also evidently decreased the inflammatory mediators. CONCLUSIONS: The poncirin treatment showed marked improvement in behavioral, biochemical and histological parameters following CCL4-induced liver injury. Additionally, the poncirin treatment also markedly improved the antioxidant enzymes, attenuated the oxidative stress markers and inflammatory cytokines.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Citocinas/metabolismo , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Tetracloreto de Carbono , Flavonoides/química , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular
20.
PLoS One ; 15(4): e0231173, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32251487

RESUMO

Acetaminophen is one of the most common over-the-counter pain medications used worldwide and is considered safe at therapeutic dose. However, intentional and unintentional overdose accounts for up to 70% of acute liver failure cases in the western world. Extensive research has demonstrated that the induction of oxidative stress and mitochondrial dysfunction are central to the development of acetaminophen-induced liver injury. Despite the insight gained on the mechanism of acetaminophen toxicity, there still is only one clinically approved pharmacological treatment option, N-acetylcysteine. N-acetylcysteine increases the cell's antioxidant defense and protects liver cells from further acetaminophen-induced oxidative damage. Because it primarily protects healthy liver cells rather than rescuing the already injured cells alternative treatment strategies that target the latter cell population are warranted. In this study, we investigated mitochondria as therapeutic target for the development of novel treatment strategies for acetaminophen-induced liver injury. Characterization of the mitochondrial toxicity due to acute acetaminophen overdose in vitro in human cells using detailed respirometric analysis revealed that complex I-linked (NADH-dependent) but not complex II-linked (succinate-dependent) mitochondrial respiration is inhibited by acetaminophen. Treatment with a novel cell-permeable succinate prodrug rescues acetaminophen-induced impaired mitochondrial respiration. This suggests cell-permeable succinate prodrugs as a potential alternative treatment strategy to counteract acetaminophen-induced liver injury.


Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Entorpecentes/efeitos adversos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Respiração Celular/efeitos dos fármacos , Overdose de Drogas/tratamento farmacológico , Mitocôndrias/metabolismo , Pró-Fármacos/farmacocinética , Ácido Succínico/farmacocinética , Acetaminofen/administração & dosagem , Acetaminofen/farmacologia , Idoso , Analgésicos não Entorpecentes/administração & dosagem , Analgésicos não Entorpecentes/farmacologia , Plaquetas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Overdose de Drogas/metabolismo , Complexo I de Transporte de Elétrons/antagonistas & inibidores , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Masculino , Mitocôndrias/efeitos dos fármacos
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