Cocoa extract protects against early alcohol-induced liver injury in the rat

Oxidants have been shown to be involved in alcohol-induced liver injury. This study was designed to determine whether cocoa flavonoid extract, composed mostly of epicatechin and epicatechin oligomers, protects against early alcohol-induced liver injury in rats. Male Wistar rats were fed high-fat liquid diets with or without ethanol (10-14 g/kg per day) and cocoa extract (400 mg/kg per day) continuously for 4 weeks using an enteral feeding protocol. Mean body weight gains ( approximately 4 g/day) were not significantly different between treatment groups. Cocoa extract did not affect average daily urine ethanol concentrations ( approximately 200mg/dL). After 4 weeks, serum alanine amino transferase levels of the ethanol group were increased nearly fourfold (110+/-16 IU/L) compared to control values (35+/-3 IU/L); this effect of ethanol was blocked by cocoa extract (60+/-6 IU/L). Additionally, enteral ethanol caused severe fat accumulation, mild inflammation, and necrosis in the liver; cocoa extract significantly blunted these changes. Increases in liver TNFalpha protein levels caused by ethanol were completely blocked by cocoa extract. Further, ethanol significantly increased the accumulation of protein adducts of 4-hydroxynonenal, a product of lipid peroxidation serving as an index of oxidative stress; again this was counteracted by the addition of cocoa extract. These results indicate that dietary flavanols such as those found in cocoa can prevent early alcohol-induced liver injury.     

Ebselen prevents early alcohol-induced liver injury in rats

Oxidants have been shown to be involved in alcohol-induced liver injury. Moreover, 2-phenyl-1,2-benzisoselenazole-3(2H)-one (ebselen), an organoselenium compound and glutathione peroxidase mimic, decreases oxidative stress and protects against stroke clinically. This study was designed to test the hypothesis that ebselen protects against early alcohol-induced liver injury in rats. Male Wistar rats were fed high-fat liquid diets with or without ethanol (10-16 g/kg/d) continuously for up to 4 weeks using the intragastric enteral feeding protocol developed by Tsukamoto and French. Ebselen (50 mg/kg twice daily, intragastrically) or vehicle (1% tylose) was administered throughout the experiment. Mean urine ethanol concentrations were not significantly different between treatment groups, and ebselen did not affect body weight gains or cyclic patterns of ethanol concentrations in urine. After 4 weeks, serum ALT levels were increased significantly about 4-fold over control values (37 +/- 5 IU/l) by enteral ethanol (112 +/- 7 IU/l); ebselen blunted this increase significantly (61 +/- 8 IU/l). Enteral ethanol also caused severe fatty accumulation, mild inflammation, and necrosis in the liver (pathology score: 4.3 +/- 0.3). In contrast, these pathological changes were blunted significantly by ebselen (pathology score: 2.5 +/- 0.4). While there were no significant effects of either ethanol or ebselen on glutathione peroxidase activity in serum or liver tissue, ebselen blocked the increase in serum nitrate/nitrite caused by ethanol. Furthermore, ethanol increased the activity of NF-kappaB over 5-fold, the number of infiltrating neutrophils 4-fold, and the accumulation of 4-hydroxynonenal over 5-fold. Ebselen blunted all of these effects significantly. These results indicate that ebselen prevents early alcohol-induced liver injury, most likely by preventing oxidative stress, which decreases inflammation.     

Red potato extract protects from D-galactosamine-induced liver injury in rats

The protective effects of red potato extract (RPE) as to liver damage were determined in D-galactosamine (GalN)-intoxicated rats. Increases in serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase activities, all of which were induced by GalN injection, decreased in RPE administered rats, suggesting that RPE acts as a functional food showing anti-hepatotoxicity.     

Hepatoprotective effects of methanolic extract of green tea against Thioacetamide-Induced liver injury in Sprague Dawley rats

Ethnopharmacological relevanceSince ancient times, herbal medicines have been applied in the treatment of cancer. Tea, derivative from the dried leaves of Camellia sinensis (L.) Kuntze plant is the most popular beverage globally after water and is available in various forms. Green tea has been expansively investigated for its beneficial properties of cancer prevention and therapy. The goal of the research: The current study was conducted to evaluate the hepaprotective character of methanolic green tea extract and its mechanism of action contrary to thioacetamide (TAA)-produced liver fibrosis of Sprague Dawley rats.Materials and MethodsThirty rodents were equally placed in 5 clusters including normal control, TAA group as a positive control, silymarin as standard drug control, and treatment groups consisting of high dose and a low dose Camellia sinensis. Rats in experimental clusters by mouth fed with C. sinensis at 250 mg/kg or 500 mg/kg daily for 2 months. After 60 days, all rats were sacrificed. Blood specimens were gathered for liver biochemical examination. Livers of all groups were dissected out and subjected to histopathological examination through the Hematoxylin and Eosin stain, Masson trichrome, and immunohistochemistry stains (PCNA). Liver tissue homogenate was also analyzed for antioxidant activity parameters.ResultsGross morphological examination showed a regular liver architecture in C. sinensis fed collections compared to the TAA sets. Histology of rat’s liver fed with C. sinensis showed an important decrease in the liver index with hepatic cells propagation, mild cellular injury, and immunostaining showed significant down-expression of proliferating cell nuclear antigen (PCNA). TAA produced liver fibrosis through a significant increase in serum alanine transferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin. Total protein and albumin also decreased in the TAA group. Moreover, the reduction of antioxidant enzyme activity including superoxide dismutase and catalase as well as the increase in malondialdehyde was detected in the TAA control group. Meanwhile, an abnormal level of liver biochemical parameters was restored closer to the normal levels in serum of the C. sinensis-fed clusters. In addition, C. sinensis fed assemblies showed elevated antioxidative enzymes activity with a reduction in malondialdehyde level comparable to the levels in silymarin-treated rats.ConclusionsGreen tea potentially inhibited the progression of liver cirrhosis, down -regulation of PCNA proliferation, prevented oxidation of hepatocytes, recovered SOD and CAT enzymes, condensed MDA and reduced cellular inflammation.     

Hepatoprotective effect of green tea (Camellia sinensis) extract against tamoxifen-induced liver injury in rats

Tamoxifen citrate (TAM), is widely used for treatment of breast cancer. It showed a degree of hepatic carcinogenesis. The purpose of this study was to elucidate the antioxidant capacity of green tea (Camellia sinensis) extract (GTE) against TAM-induced liver injury. A model of liver injury in female rats was done by intraperitoneal injection of TAM in a dose of 45mg Kg(-1) day(-1), i.p. for 7 successive days. GTE in the concentration of 1.5 %, was orally administered 4 days prior and 14 days after TAM-intoxication as a sole source of drinking water. The antioxidant flavonoid; epicatechin (a component of green tea) was not detectable in liver and blood of rats in either normal control or TAM-intoxicated group, however, TAM intoxication resulted in a significant decrease of its level in liver homogenate of tamoxifenintoxicated rats. The model of TAM-intoxication elicited significant declines in the antioxidant enzymes (glutathione-S-transferase,glutathione peroxidase, superoxide dismutase and catalase) and reduced glutathione concomitant with significant elevations in TBARS (thiobarbituric acid reactive substance) and liver transaminases; sGPT (serum glutamate pyruvate transaminase) and sGOT (serum glutamate oxaloacetate transaminase) levels. The oral administration of 1.5 % GTE to TAM-intoxicated rats, produced significant increments in the antioxidant enzymes and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases levels. The data obtained from this study speculated that 1.5 % GTE has the capacity to scavenge free radical and can protect against oxidative stress induced by TAM intoxication. Supplementation of GTE could be useful in alleviating tamoxifen-induced liver injury in rats.     

Reduced early alcohol-induced liver injury in CD14-deficient mice

Activation of Kupffer cells by gut-derived endotoxin is associated with alcohol-induced liver injury. Recently, it was shown that CD14-deficient mice are more resistant to endotoxin-induced shock than wild-type controls. Therefore, this study was designed to investigate the role of CD14 receptors in early alcohol-induced liver injury using CD14 knockout and wild-type BALB/c mice in a model of enteral ethanol delivery. Animals were given a high-fat liquid diet continuously with ethanol or isocaloric maltose-dextrin as control for 4 wk. The liver to body weight ratio in wild-type mice (5.8 +/- 0.3%) was increased significantly by ethanol (7.3 +/- 0.2%) but was not altered by ethanol in CD14-deficient mice. Ethanol elevated serum alanine aminotransferase levels nearly 3-fold in wild-type mice, but not in CD14-deficient mice. Wild-type and knockout mice given the control high-fat diet had normal liver histology, whereas ethanol caused severe liver injury (steatosis, inflammation, and necrosis; pathology score = 3.8 +/- 0.4). In contrast, CD14-deficient mice given ethanol showed minimal hepatic changes (score = 1.6 +/- 0.3, p < 0.05). Additionally, NF-kappa B, TGF-beta, and TNF-alpha were increased significantly in wild-type mice fed ethanol but not in the CD14 knockout. Thus, chronic ethanol feeding caused more severe liver injury in wild-type than CD14 knockouts, supporting the hypothesis that endotoxin acting via CD14 plays a major role in the development of early alcohol-induced liver injury.     

Hepatoprotective effect of gastrodin against alcohol-induced liver injury in mice

Journal of Physiology and Biochemistry - Alcoholic liver disease (ALD) is a common and serious threat to human health worldwide. In this study, the hepatoprotective effect of gastrodin against...     

Green tea metabolite EGCG protects membranes against oxidative damage in vitro

Green tea polyphenols like epigallocatechin gallate (EGCG) have been proposed as a cancer chemopreventative. Several studies have shown that EGCG can act as an antioxidant by trapping proxyl radicals and inhibiting lipid peroxidation. The main propose of this study is to investigate the antioxidant capacity of EGCG using erythrocyte membrane-bound ATPases as a model. The effects of EGCG on t-butylhydroperoxide-induced lipid peroxidation and the activity of membrane-bound ATPases in human erythrocyte membranes were studied. The extent of oxidative damage in membranes was assessed by measuring lipid peroxidation, (TBARS, thiobarbituric acid reactive substances formation) and the activity of ATPases (Na(+)/K(+), Ca(2+), and CaM-activated Ca(2+) pump ATPases). EGCG blocked t-BHP induced lipid peroxidation in erythrocyte membranes, significantly (0.45 +/- 0.02 vs 0.20 +/- 0.01; t-BHP vs t-BHP + EGCG respectively, microm/L TBARS) (p < 0.05). EGCG also protected ATPases against t-BHP induced damage; for Na/K ATPase (2.4 +/- 0.2 vs 1.6 +/- 0.1 vs 2.44 +/- 0.2, nmol Pi/min/mg protein, control vs t-BHP vs t-BHP and EGCG respectively), for Ca ATPase (5.8 +/- 0.4 vs 3.9 +/- 0.3 vs 5.6 +/- 0.34, nmol Pi/min/mg protein, control vs t-BHP vs t-BHP and EGCG respectively) and for CaM-Ca ATPase (14.7 +/- 0.7 vs 7.3 +/- 0.4 vs 11.6 +/- 0.55, nmol Pi/min/mg protein, control vs t-BHP vs t-BHP and EGCG respectively) (p < 0.05). In conclusion our results indicate that EGCG is a powerful antioxidant that is capable protecting erythrocyte membrane-bound ATPases against oxidative stress.     

Hepatoprotective effects of purple potato extract against D-galactosamine-induced liver injury in rats

We investigated the hepatoprotective effect of purple potato extract (PPE) against D-galactosamine (GalN)-induced liver injury in rats. PPE (400 mg) was administered once daily for 8 d, and then GalN (250 mg/kg of body weight) was injected at 22 h before the rats were killed. Serum tumor necrosis factor alpha (TNF-alpha), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and asparate aminotranferase (AST) levels increased significantly after injection of GalN, but PPE inhibited GalN-induced alterations in serum TNF-alpha, LDH, ALT, and AST levels. Hepatic lipid peroxide and glutathione levels in the control + GalN group were higher and lower respectively than those in the control group, and those in the PPE + GalN group did not differ from that in the control group. The lipid peroxide level in hepatic microsomes treated with 2,2'-azobis (2-amidinopropane) dihydrochloride in the PPE group was significantly lower than that in the control group. This suggests that PPE has hepatoprotective effects against GalN-induced hepatotoxicity via inhibition lipid peroxidation and/or inflammation in rats.     

Role of lipopolysaccharide-binding protein in early alcohol-induced liver injury in mice

Cellular responses to endotoxins are enhanced markedly by LPS-binding protein (LBP). Furthermore, it has been demonstrated that endotoxins and proinflammatory cytokines such as TNF-alpha participate in early alcohol-induced liver injury. Therefore, in this study, a long-term intragastric ethanol feeding model was used to test the hypothesis that LBP is involved in alcoholic hepatitis by comparing LBP knockout and wild-type mice. Two-month-old female mice were fed a high-fat liquid diet with either ethanol or isocaloric maltose-dextrin as control continuously for 4 wk. There was no difference in mean urine alcohol concentrations between the groups fed ethanol. Dietary alcohol significantly increased liver to body weight ratios and serum alanine aminotransferase levels in wild-type mice (189 +/- 31 U/L) over high-fat controls (24 +/- 7 U/L), effects which were blunted significantly in LBP knockout mice (60 +/- 17 U/L). Although no significant pathological changes were observed in high-fat controls, 4 wk of dietary ethanol caused steatosis, mild inflammation, and focal necrosis in wild-type animals as expected (pathology score, 5.9 +/- 0.5). These pathological changes were reduced significantly in LBP knockout mice fed ethanol (score, 2.6 +/- 0.5). Endotoxin levels in the portal vein were increased significantly after 4 wk in both groups fed ethanol. Moreover, ethanol increased TNF-alpha mRNA expression in wild-type, but not in LBP knockout mice. These data are consistent with the hypothesis that LBP plays an important role in early alcohol-induced liver injury by enhancing LPS-induced signal transduction, most likely in Kupffer cells.     

Depression by a green tea extract of alcohol-induced oxidative stress and lipogenesis in rat liver

We determined the effects of a green tea extract with 36% alcohol on the blood alcohol content, oxidative stress, lipogenesis, inflammation and liver function of female Wistar rats. Tea alcohol significantly decreased the O??, H?O? and HOCl amounts via catechins and not caffeine. Thirty days of alcohol gavage improved the level of reactive oxygen species (ROS) in the liver, bile and blood, increased the 4-hydroxynonenal-protein adducts, Kupffer cell infiltration and lipid accumulation in the liver, and elevated the plasma alanine aminotransferase level. A western blot analysis showed reduced expression of the oxidative enzymes (CYP2E1 and NADPH oxidase p47phox protein) and lipogenic enzymes (SREBP-1c and fatty acid synthase) in the alcohol-treated liver. Tea alcohol significantly attenuated these elevated parameters. We conclude that the green tea extract in alcohol efficiently reduced the amounts of O??, H?O? and HOCl primarily due to the catechin content, and not caffeine. The developed tea liquor attenuated alcohol-induced oxidative injury and lipogenesis in the liver by the synergetic action of catechins and caffeine.     

Green tea extract supplement reduces D-galactosamine-induced acute liver injury by inhibition of apoptotic and proinflammatory signaling

Oxidative stress and inflammation contributed to the propagation of acute liver injury (ALI). The present study was undertaken to determine whether D-galactosamine (D-GalN) induces ALI via the mitochondrial apoptosis- and proinflammatory cytokine-signaling pathways, and possible mechanism(s) by which green tea (GT) extract modulates the apoptotic and proinflammatory signaling in rat. D-GalN induced hepatic hypoxia/hypoperfusion and triggered reactive oxygen species (ROS) production from affected hepatocytes, infiltrated leukocytes, and activated Kupffer cells. D-GalN evoked cytosolic Bax and mitochondrial cytochrome C translocation and activated proinflammatory nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) translocation, contributing to the increase of intercellular adhesion molecule-1 expression, terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL)-positive hepatocytes, multiple plasma cytokines and chemokines release, and alanine aminotransferase (ALT) activity. An altered biliary secretion profile of several acute phase proteins directly indicates oxidative stress affecting intracellular trafficking in the hepatocyte. GT pretreatment attenuated ROS production, mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, plasma ALT and cytokines levels, biliary acute phase proteins secretion and hepatic pathology by the enhancement of anti-apoptotic mechanisms. In conclusion, D-GalN induced ALI via hypoxia/hypoperfusion-enhanced mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, contributing to oxidative stress and inflammation in the liver. GT can counteract the D-GalN-induced ALI via the attenuation of apoptotic and proinflammatory signaling by the upregulation of anti-apoptotic mechanism.     

Interleukin-22 protects against acute alcohol-induced hepatotoxicity in mice

The protective effects of interleukin-22 (IL-22) on acute alcohol-induced liver injury were investigated. Mice were gavaged with 7 doses of alcohol (56% wt/vol, 15.2 mL/kg of body weight for each dose) over the 24 h, and IL-22 (0.5 mg/kg BW) was given to the mice by injection into the tail vein 1 h after alcohol administration. The results indicated that acute alcohol administration caused prominent hepatic microvesicular steatosis and an elevation of serum transaminase activities, induced a significant decrease in hepatic glutathione in conjunction with enhanced lipid peroxidation, and increased hepatocyte apoptosis as well as hepatic TNF-alpha production. IL-22 treatment attenuated these adverse changes induced by acute alcohol administration. The protective effects of IL-22 on alcohol-induced hepatotoxicity were due mainly to its anti-inflammatory, anti-oxidant, and anti-apoptotic features.     

Green tea polyphenol extract attenuates colon injury induced by experimental colitis

Inflammatory bowel disease (IBD) is characterised by oxidative and nitrosative stress, leukocyte infiltration, and up-regulation of intercellular adhesion molecule 1 (ICAM-1) expression in the colon. The aim of the present study was to examine the effects of green tea extract in rats subjected to experimental colitis induced by intracolonic instillation of dinitrobenzene sulphonic acid (DNBS). At 4 days after DNBS administration the rats were sacrificed. Treatment with green tea extract significantly attenuated diarrhoea and loss of body weight. This was associated with a remarkable amelioration of the disruption of the colonic architecture, significant reduction of colonic myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-alpha) production. Green tea extract also reduced the appearance of nitrotyrosine immunoreactivity in the colon and reduced the up-regulation of ICAM-1.     

Betaine supplementation protects against high-fructose-induced renal injury in rats

High fructose intake causes metabolic syndrome, being an increased risk of chronic kidney disease development in humans and animals. In this study, we examined the influence of betaine on high-fructose-induced renal damage involving renal inflammation, insulin resistance and lipid accumulation in rats and explored its possible mechanisms. Betaine was found to improve high-fructose-induced metabolic syndrome including hyperuricemia, dyslipidemia and insulin resistance in rats with systemic inflammation. Betaine also showed a protection against renal dysfunction and tubular injury with its restoration of the increased glucose transporter 9 and renal-specific transporter in renal brush bolder membrane and the decreased organic anion transporter 1 and adenosine-triphosphate-binding cassette transporter 2 in the renal cortex in this model. These protective effects were relevant to the anti-inflammatory action by inhibiting the production of inflammatory cytokines including interleukin (IL)-1β, IL-18, IL-6 and tumor necrosis factor-α in renal tissue of high-fructose-fed rat, being more likely to suppress renal NOD-like receptor superfamily, pyrin domain containing 3 inflammasome activation than nuclear factor κB activation. Subsequently, betaine with anti-inflammation ameliorated insulin signaling impairment by reducing the up-regulation of suppressor of cytokine signaling 3 and lipid accumulation partly by regulating peroxisome proliferator-activated receptor α/palmityltransferase 1/carnitine/organic cation transporter 2 pathway in kidney of high-fructose-fed rats. These results indicate that the inflammatory inhibition plays a pivotal role in betaine’s improvement of high-fructose-induced renal injury with insulin resistance and lipid accumulation in rats.     

Estradiol protects against ischemic brain injury in middle-aged rats

Several clinical studies suggest that estradiol acts as a potent growth and protective factor in the adult brain. Postmenopausal women experience permanent hypoestrogenicity and suffer from increased risk of brain injury associated with neurodegenerative diseases such as stroke and Alzheimer's disease. Estrogen replacement therapy appears to decrease the risk and severity of these neurodegenerative conditions. Studies using animal models have shown that estradiol exerts similar effects in rodents and can enhance cell survival and induce synaptic plasticity. Therefore, we undertook studies to assess whether estradiol treatment can decrease brain injury and cell death induced by an experimental model of ischemia and whether aging animals remain responsive to the protective effects of estradiol. We will review results from recent studies that demonstrate that 1) in young animals, estrogens exert profound protective effects against ischemic brain injury induced by cerebral artery occlusion and 2) the response of aging animals has been tested with varying results. We will discuss and compare our experimental findings that utilize a permanent cerebral artery occlusion model and physiological levels of estradiol replacement therapy in young and middle-aged rats with those of previous studies. These observations provide important insights into the potential protective actions of estrogen replacement therapy on age- and disease-related processes in the brain.     

Protective effects of sodium nitrite preconditioning against alcohol-induced acute liver injury in mice

The purpose of the present study was to investigate the effect of sodium nitrite (SN) on alcohol-induced acute liver injury in mice. Forty male C57bL/6 mice were randomly divided into 4 groups. Acute alcohol-induced liver injury group were injected intraperitoneal (ip) with alcohol (4.5 g/kg); SN preconditioning group were pretreated with SN (16 mg/kg, ip) for 12 h, and received alcohol (4.5 g/kg, ip) injection; Control and SN groups were treated with saline and SN, respectively. After the treatments, liver index (liver/body weight ratio) was determined. Colorimetric technique was performed to measure the serum alanine transaminase (ALT), aspartate transaminase (AST), liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities, as well as malondialdehyde (MDA) content. The pathological index of liver tissue was assayed by HE and TUNEL fluorometric staining. Using Western blot and immunohistochemistry staining, the expression of hypoxia-inducible factor-1α (HIF-1α) protein was detected. The results showed that, compared with acute alcohol-induced liver injury group, pretreatment with low doses of SN decreased liver index and serum levels of ALT and AST, weakened acute alcohol-induced hepatocyte necrosis, improved pathological changes in liver tissue, increased live tissue SOD, GSH-Px and CAT activities, reduced MDA content and apoptosis index of hepatocytes, and up-regulated HIF-1α protein level in liver tissue. These results suggest that the pretreatment of SN can protect hepatocytes against alcohol-induced acute injury, and the protective mechanism involves inhibition of oxidative stress and up-regulation of HIF-1α protein level.