Ya Ling Chen

Protective effect of Acacia confusa bark extract and its active compound gallic acid against carbon tetrachloride-induced chronic liver injury in rats

Acacia confusa Merr. (Leguminosae), a species native to Taiwan, is widely distributed on the hills and lowlands of Taiwan, and has been traditionally used as a medicine. The hepatoprotective effects of A. confusa bark extract (ACBE) and its active constituent gallic acid were evaluated against carbon tetrachloride (CCl(4))-induced hepatotoxicity in rats. CCl(4)-induced hepatic pathological damage and significantly increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA) in plasma, and cytochrome P4502E1 (CYP2E1) protein expression in hepatic samples, and decreased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) in erythrocytes. Treatment with ACBE, gallic acid or silymarin could decrease significantly the AST, ALT, and MDA levels in plasma, and CYP2E1 expression in liver tissues, and increase the activities of SOD and GPX in erythrocyte when compared with CCl(4)-treated group. Liver histopathology also showed that ACBE, gallic acid or silymarin could significantly reduce the incidence of liver lesions induced by CCl(4). These results suggested that the ACBE and gallic acid exhibit potent hepatoprotection against CCl(4)-induced liver damages in rats, and the hepatoprotective effects of ACBE and gallic acid may be due to the modulation of antioxidant enzymes activities and inhibition of lipid peroxidation and CYP2E1 activation.

Effect of schisandrin B and sesamin mixture on CCl4-induced hepatic oxidative stress in rats

To study the effects of schisandrin B and sesamin mixture on carbon tetrachloride (CCl4)‐induced hepatic oxidative stress in male Sprague‐Dawley rats. The rats were randomly assigned to five groups: control group (olive oil injection), CCl4 group (CCl4 injection), silymarin group (CCl4 injection combined with supplementation of silymarin, 7.5 mg/kg/day), low dose group (CCl4 injection combined with supplementation of schisandrin B and sesamin mixture at a low dose, 43 mg/kg/day) and high dose group (CCl4 injection combined with the supplementation of schisandrin B and sesamin mixture at a high dose, 215 mg/kg/day). The hepatic superoxide dismutase and glutathione peroxidase activities of rats in the low dose and high dose groups were increased significantly compared with those in the CCl4 group. The hepatic reduced glutathione concentration in the silymarin, low dose and high dose groups were increased significantly (48%, 45% and 53%, respectively) when compared with those of the CCl4 group. In addition, the concentration of glutathione in the erythrocytes of the low dose group was significantly higher than the CCl4 group by 25%. These results suggest that the schisandrin B–sesamin mixture exerted a hepatoprotective effect by improving the antioxidative capacity in rats under CCl4‐induced hepatic oxidative stress. Copyright

β-Carotene exhibits antioxidant and anti-apoptotic properties to prevent ethanol-induced cytotoxicity in isolated rat hepatocytes

The study was designed to evaluate the effects of 1 μM β‐carotene on antioxidant status in ethanol‐treated rat hepatocytes and investigate possible anti‐apoptotic mechanisms of β‐carotene in protecting ethanol‐induced cytotoxicity. The isolated rat hepatocytes were incubated for 48 h in a medium with or without alcohol (100 mM) and μ‐carotene (1 μM) using the following groups: the control (C), β‐carotene (CB), ethanol (E), and ethanol + β‐carotene (EB) groups. The cell viability, antioxidative status, cytochrome P450 2E1 (CYP2E1) and caspase expressions in hepatocytes were measured. The E group demonstrated lower cell viability, glutathione (GSH) levels, and lipid peroxide accumulation in rat hepatocytes; meanwhile, CYP2E1, caspase‐3, and caspase‐9 expressions increased. In contrast, cell viability, GSH levels, and glutathione reductase (GRD) activity significantly increased while lipid peroxides and expressions of CYP2E1, casapse‐3, and caspase‐9 decreased in the EB group. The results suggest that ethanol treatment decreases cell viability in rat hepatocytes via induced oxidative stress. 1 μM β‐carotene decreased oxidative stress and prevented ethanol‐induced cell death by inhibiting caspase‐9 and caspase‐3 expression. Copyright

Effects of glutamine administration on inflammatory responses in chronic ethanol-fed rats

The purpose of this study was to investigate the effects of glutamine supplementation on inflammatory responses in chronic ethanol-fed rats. Male Wistar rats weighing about 160 g were divided into five groups. Two groups were fed a normal liquid diet and three groups were fed a glutamine-containing liquid diet. After 1 week, one of the normal liquid diet groups was fed an ethanol-containing liquid diet (CE), and the other group served as the control (CC) group. At the same time, one of the glutamine-containing liquid diet groups was continually fed the same diet (GCG), but the other two groups were fed ethanol-containing diet supplemented with glutamine (GEG) or without glutamine (GE). The following items were analyzed: (1) liver function, (2) cytokine contents, and (3) hepatic oxidative stress. The activities of aspartate transaminase (AST) and alanine transaminase (ALT) and levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the CE group had significantly increased. In addition, hepatic cytochrome P450 2E1 (CYP2E1) expression had significantly increased in the CE, GE and GEG groups. However, the activities of AST and ALT and levels of TNF-α and IL-1β in the GE group were significantly lower than those of the CE group. The results suggest that the plasma inflammatory responses of rats fed an ethanol-containing liquid diet for 7 weeks significantly increased. However, pretreatment with glutamine improved the plasma inflammatory responses induced by ethanol.

Antioxidative status of patients with alcoholic liver disease in southeastern Taiwan

AIM To investigate the antioxidative status of patients with alcoholic liver disease (ALD) in southeastern Taiwan. METHODS Our study comprised 27 patients with ALD recruited from Taitung Mackay Memorial Hospital, located in southeastern Taiwan. Patients with ALD included 12 non-aborigines (12 men) and 15 aborigines (11 men and 4 women). According to the severity of ALD, patients with ALD included 10 with hepatitis (9 men and 1 woman) and 17 with cirrhosis (14 men and 3 women). Twenty-two age- and gender-matched healthy adults served as the control group in this study. Venous blood (10 mL) of each subject was drawn into EDTA-containing tubes after 8 h overnight fasting. RESULTS Compared to the control group, patients with ALD showed significantly lower erythrocytic catalase (11.1 ± 0.7 U/mg Hb vs 8.0 ± 0.7 U/mg Hb, P < 0.05) and superoxide dismutase (9.5 ± 1.6 U/mg Hb vs 3.0 ± 0.2 U/mg Hb, P < 0.05) activities. Furthermore, the erythrocytic reduced glutathione/oxidized glutathione ratio was significantly lower in ALD patients than that in the control group (38.1 ± 5.4 vs 15.7 ± 1.9, P < 0.05). The results revealed that patients with ALD experienced more oxidative stress than those in the control group. The non-aboriginal, but not the aboriginal, ALD group had higher erythrocytic glutathione peroxidase (GPX) activity than that in the control group (46.1 ± 7.8 U/g Hb vs 27.9 ± 2.2 U/g Hb, P < 0.05). Hepatitis, but not cirrhosis, ALD patients had higher erythrocytic GPX activity than that in the control group (44.3 ± 8.6 U/g Hb vs 27.9 ± 2.2 U/g Hb, P < 0.05). CONCLUSION Our results indicate that both ethnicity and the severity of ALD may cause different erythrocytic antioxidative enzyme activities especially GPX activity.

Epidermal growth factor improved alcohol-induced inflammation in rats

The purpose of this study was to investigate the effects of an epidermal growth factor (EGF) intervention on improving the inflammatory response of rats fed an ethanol-containing diet. Eight-week-old male Wistar rats were divided into ethanol (E) and control (C) groups. Rats in the E group were fed an ethanol liquid diet, while rats in the C group were pair-fed an isoenergetic diet without ethanol. After a 4-week ethanol-induction period, both the C and E group were respectively subdivided into 2 groups: a normal liquid diet without (C group, n = 8) or with EGF supplementation (C + EGF, n = 8), and the ethanol-containing diet without (E group, n = 8) or with EGF supplementation (E + EGF group, n = 8). The EGF (30 μg/kg body weight/day) intervention period was carried out for the following 8 weeks. At the end of the experiment, activity of aspartate transaminase (AST) and alanine transaminase (ALT) and hepatic levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 in group E were significantly higher than those in group C. In addition, alterations in the gut microbiota profile were found in group E. In contrast, activity of AST and ALT and levels of TNF-α, IL-1β, and IL-6 in group E + EGF were significantly lower than those in group E. Significantly lower intestinal permeability and lower numbers of Escherichia coli in the fecal microbial culture were also found in group E + EGF. These results suggest that EGF improved the intestinal integrity by decreasing E. coli colonization and lowering intestinal permeability, which then ameliorated the inflammatory response under chronic ethanol exposure.

Dietary saturated fatty acids reduce hepatic lipid accumulation but induce fibrotic change in alcohol-fed rats.

BACKGROUND In this study, we evaluated the influence of an ethanol-containing diet with high saturated fatty acids (SFAs) on alcoholic liver disease (ALD) in rats. METHODS Male Wistar rats weighing about 160 g were divided into four groups: an ethanol (E) group fed an ethanol-containing liquid diet with 36% total calories as fat (corn oil, olive oil and safflower oil); a control (C) group pair-fed an isoenergetic diet without ethanol; an ethanol with saturated fat (EHS) group fed an ethanol-containing diet which contained 40% total calories as fat (90% lard); and a control with saturated fat (CHS) group fed an isoenergetic diet without ethanol, which contained 40% total calories as fat. RESULTS After 8 weeks of treatment, the liver weight and plasma aspartate aminotransferase (AST) activities in E and EHS groups were significantly higher than those of C group. Significantly higher scores of inflammation, necrosis, and fatty changes were found in E group, whereas significantly higher scores of necrosis, bile duct hyperplasia, and fibrosis were found in EHS group. Although significantly lower plasma adiponectin concentrations were observed in both E and EHS groups, compared to C group, plasma adiponectin in EHS group was significantly higher than that in E group. There was no change in hepatic peroxisome proliferator activated receptor (PPAR)-α expression between E and C groups, and rats in EHS group showed a significantly elevated level compared to the other groups. A lower hepatic sirtuins (SIRT)-1 level was found in E group, but it did not reach statistical significance. Moreover, the highest plasma TGF-β1 level was found in EHS group. Compared to C group, the hepatic reduced glutathione/oxidized glutathione ratio and thiobarbituric acid (TBA)-reactive substance level were significantly increased in E and EHS groups; however, there was no significant difference between E and EHS groups. Significantly increased hepatic CYP2E1 expression was observed in both E and EHS groups, while at the same time, hepatic CYP2E1 in EHS group was the highest among all groups. The hepatic tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 concentrations in the E group were significantly higher than those in C group, whereas the hepatic IL-6 and IL-10 concentrations in ES group were significantly lower than those of E group. CONCLUSIONS These results suggested that dietary saturated fats may inhibit hepatic fat accumulation and induce hepatic fibrosis in rats under chronic alcohol intake.

The antiapoptotic effects of different doses of β-carotene in chronic ethanol-fed rats

BACKGROUND Ethanol consumption might induce hepatic apoptosis and cause liver damage. The study was to investigate the effects of different doses of β-carotene supplementation on the antioxidant capacity and hepatic apoptosis in chronic ethanol-fed rats. METHODS Rats were divided into 6 groups: C (control liquid diet), CLB [control liquid diet with β-carotene supplementation at 0.52 mg/kg body weight (BW)/day], CHB (control liquid diet with β-carotene supplementation at 2.6 mg/kg BW/day), E (ethanol liquid diet), ELB (ethanol liquid diet with β-carotene supplementation at 0.52 mg/kg BW/day), and EHB (ethanol liquid diet with β-carotene supplementation at 2.6 mg/kg BW/day). After 12 weeks, rats were sacrificed and blood and liver samples were collected for analysis. RESULTS Lipid peroxidation and hepatic cytochrome P450 2E1 (CYP2E1) expression had increased, and hepatic Fas ligand, caspase-8, cytochrome c, caspase-9, and -3 expressions had significantly increased in the E group. However, lipid peroxidation and CYP2E1, caspase-9, and -3 expressions were significantly lower and Bcl-xL expression was higher in the ELB group. The hepatic tumor necrosis factor (TNF)-α level, lipid peroxidation, and cytochrome c expression were significantly lower and Bcl-2 expression was significantly higher in the EHB group. CONCLUSIONS The results suggest that ethanol treatment causes oxidative stress and hepatic apoptosis leading to liver injury, and β-carotene supplementation (0.52 mg/kg BW/day) can prevent ethanol-induced liver damage by decreasing ethanol-induced oxidative stress and inhibiting apoptosis in the liver.