RESUMO
OBJECTIVE: To investigate the phenolic composition, antioxidant properties, and hepatoprotective mechanisms of polyphenols from green tea extract (GTP) in carbon tetrachloride (CCl4)-induced acute liver injury mouse model. METHODS: High-performance liquid chromatography was used to analyze the chemical composition of the extract. Antioxidant activity of GTP was assessed by O2â-, OHâ, DPPHâ, and ferric-reducing antioxidant power (FRAP) assay in vitro. Sixty Kunming mice were divided into 6 groups including control, model, low-, medium-, and high-doses GTP (200, 400, 800 mg/kg) and vitamin E (250 mg/kg) groups, 10 in each group. GTP and vitamin E were administered at a level of abovementioned doses twice per day for 7 days prior to exposure to a single injection of CCl4. Hepatoprotective effects of GTP were evaluated in a CCl4-induced mouse model of acute liver injury, using commercial enzyme linked immunosorbent assay kits, histopathological observation, terminal deoxynucleotidyl transferase-mediated dUTPNick-end labeling (TUNEL) assay and Western blot. RESULTS: GTP contained 98.56 µg gallic acid equivalents per milligram extract total polyphenols, including epicatechingallate, epigallocatechin gallate, epicatechin, and epigallocatechin. Compared with the model group, low-, medium-, or high doses GTP significantly decreased serum levels of alanine aminotransferase and aspartate transaminase (P<0.01). Histopathological observation confirmed that pretreatment of GTP prevented swelling and necrosis in CCl4-exposed hepatocytes. Hepatoprotective effects of low-, medium-, and high-dose GTP were associated with eliminating free radicals and improving superoxide dismutase, catalase, and glutathione peroxidase activity in the liver. Additionally, low-, medium-, and high-dose GTP decreased cell apoptosis in the CCl4-exposed liver (P<0.01). Phosphorylated nuclear factor kappa-B (NF-κB), p53, Bcl-2 associated x protein/B-cell lymphoma/leukemia-2 gene, cytochrome C, and cleaved caspase-3 levels were downregulated compared with the model group (P<0.01). CONCLUSION: GTP achieves hepatoprotective effects by improving hepatic antioxidant status and preventing cell apoptosis through caspase-3-dependent signaling pathways.
Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Chá , Animais , Antioxidantes/química , Biomarcadores/sangue , Tetracloreto de Carbono/toxicidade , Caspase 3/metabolismo , China , Modelos Animais de Doenças , Masculino , Camundongos , Extratos Vegetais/química , Polifenóis/químicaRESUMO
OBJECTIVE: To investigate effect of Sanhuangyinchi decoction (SHYCD) on liver damage and the pro-apoptotic factor caspase-3 in rats with acute hepatic failure. METHODS: SD rats were randomly divided into blank control group, model group, Angongniuhuang group (AGNH) and SHYCD group. Acute hepatic failure was induced in the rats by intraperitoneal injections of D-GaLN and LPS, and the death rate, ALT, TBIL, PT and caspase-3 activity was observed or tested. RESULTS: At 36 h after the injections, the death rate of the rats was 74.29% (26/35) in the model group, 31.43% (11/35) in AGNH group and 28.57%(10/35) in SHYCD group. The death rate, ALT, TBIL, PT and caspase-3 activity in AGNH and SHYCD groups were significantly lower than those in the model group (P<0.01). SHYCD showed stronger effect than AGNH in depressing TBIL and the activity of caspase-3 (P<0.05). CONCLUSION: SHYCD can improve the liver function and inhibit the activity of caspase-3 in rats, which can be the possible mechanism for its therapeutic effect against acute hepatic failure.
Assuntos
Caspase 3/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Falência Hepática Aguda/metabolismo , Fígado/metabolismo , Animais , Apoptose , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Fígado/efeitos dos fármacos , Fígado/patologia , Falência Hepática Aguda/tratamento farmacológico , Falência Hepática Aguda/patologia , Masculino , Fitoterapia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To observe the changes in the hemodynamics of rats with immunological liver fibrosis and explore the pathogenesis of "blood stasis" in liver fibrosis. METHODS: Rat models of liver fibrosis were established by multiple intraperitoneal injections of pig serum. The hematocrit, blood viscosity at the shear rate of 150/s, 30/s, 5/s, and 1/s, serum markers for liver fibrosis, and serum transaminase levels were measured in the control and model rats. RESULTS: The hematocrit, blood viscosity at different shear rates, hyaluronic acid (HA), laminin (LN), procollagen type III (PCIII), type IV collagen (CIV), glutamic-pyruvic transaminase (ALT) and glutamic-oxaloacetic transaminase (AST) increased significantly in the rats with experimental liver fibrosis appeared as compared with those in the control rats. Positive correlations were noted between blood viscosity at different shear rates and serum concentrations of the fibrosis markers (HA, LN, PCIII, and CIV) in the model rats. CONCLUSION: The changes in the hemodynamics in rats with immunological liver fibrosis suggests the role of "blood stasis" in the pathogenesis of liver fibrosis and provide experimental evidence for therapies to "activate the blood circulation and dissipate blood stasis" for treatment of liver fibrosis.
Assuntos
Hemodinâmica/fisiologia , Cirrose Hepática Experimental/sangue , Medicina Tradicional Chinesa , Animais , Viscosidade Sanguínea , Diagnóstico Diferencial , Feminino , Cirrose Hepática Experimental/imunologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
AIM: To investigate the protective effect of medical ozone (O(3)) combined with Traditional Chinese Medicine (TCM) Yigan Fuzheng Paidu Capsules (YC) against carbon tetrachloride (CCl(4))-induced hepatic injury in dogs. METHODS: Thirty healthy dogs were divided randomly into five groups (n = 6 in each group), namely control, oleanolic acid tablet (OAT), O(3), YC and O(3) + YC, given either no particular pre-treatment, oral OAT, medical ozone rectal insulfflation every other day, oral YC, or oral YC plus medical ozone rectal insulfflation every other day, respectively, for 30 consecutive days. After pre-treatment, acute hepatic injury was induced in all dogs with a single-dose intraperitoneal injection of CCl(4). General condition and survival time were recorded. The biochemical and hematological indexes of alanine aminotransferase (ALT), aspartate aminotransferase/alanine aminotransferase (AST/ALT), serum total bilirubin (TBIL), prothrombin time (PT), blood ammonia (AMMO), and blood urea nitrogen (BUN) were measured after CCl(4) injection. Hepatic pathological changes were also observed. RESULTS: Compared to the other four groups, the changes of group O(3) + YC dogs' general conditions (motoricity, mental state, eating, urination and defecation) could be better controlled. In group O(3) + YC the survival rates were higher (P < 0.05 vs group control). AST/ALT values were kept within a normal level in group O(3) + YC. Hepatic histopathology showed that hepatic injury in group O(3) + YC was less serious than those in the other four groups. CONCLUSION: Medical ozone combined with TCM YC could exert a protective effect on acute liver injury induced by CCl(4).
Assuntos
Intoxicação por Tetracloreto de Carbono/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Medicina Tradicional Chinesa , Ozônio/uso terapêutico , Animais , Intoxicação por Tetracloreto de Carbono/sangue , Intoxicação por Tetracloreto de Carbono/patologia , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Cães , Fígado/patologiaRESUMO
OBJECTIVE: To investigate the protective effect of Yigan Fuzheng Paidu Capsules (YC) combined with medical ozone against hepatic injury in dogs induced by hepatotoxic drug. METHODS: Twenty-four dogs were randomized equally into 4 groups (n=6), namely the model group, oleanolic acid tablet (OAT) group, YC group and YC+O(3) group, given either no particular treatment, oral OAT at 10 mg/day, oral YC at 0.2 g/day, or YC at 0.2 g/day plus 150 ml medical ozone transrectal insufflation every other day, respectively, for totally 30 consecutive days. Acute hepatic injury was induced after the treatment in the dogs with a sing-dose intraperitoneal injection of 0.9 ml/kg CCl(4) and peanut oil mixture (1:1, W/W). The general condition, survival time, alanine aminotransferase (ALT), aspartate aminotransferase/alanine aminotransferase (AST/ALT), serum total bilirubin (TBIL), prothrombin time (PT), blood ammonia (AMMO), and blood urea nitrogen (BUN) were recorded or measured. The hepatic pathological changes were observed upon death or on day 15 following CCl(4) injection. RESULTS: Compared with the other 3 treatment protocols, YC plus O(3) showed favorable effects on the activity, mental state, diet, urination and defecation of the dogs, which had significantly higher survival rate and higher levels of ALT, TBIL, PT, and AMMO than the model and OAT groups (P<0.05). AST/ALT remained normal in YC+O(3) group, which had also milder hepatic injury than the other 3 groups. CONCLUSIONS: YC combined with medical ozone may decrease transaminase and blood ammonia levels, relieve jaundice, prolong the survival time of dogs with CCl(4)-induced hepatic injury.