Hepatic Lipid Peroxidation Levels Research Articles

Cytochrome P450-2E1 promotes aging-related hepatic steatosis, apoptosis and fibrosis through increased nitroxidative stress

The role of ethanol-inducible cytochrome P450-2E1 (CYP2E1) in promoting aging-dependent hepatic disease is unknown and thus was investigated in this study. Young (7 weeks) and aged female (16 months old) wild-type (WT) and Cyp2e1-null mice were used in this study to evaluate age-dependent changes in liver histology, steatosis, apoptosis, fibrosis and many nitroxidative stress parameters. Liver histology showed that aged WT mice exhibited markedly elevated hepatocyte vacuolation, ballooning degeneration, and inflammatory cell infiltration compared to all other groups. These changes were accompanied with significantly higher hepatic triglyceride and serum cholesterol in aged WT mice although serum ALT and insulin resistance were not significantly altered. Aged WT mice showed the highest rates of hepatocyte apoptosis and hepatic fibrosis. Further, the highest levels of hepatic hydrogen peroxide, lipid peroxidation, protein carbonylation, nitration, and oxidative DNA damage were observed in aged WT mice. These increases in the aged WT mice were accompanied by increased levels of mitochondrial nitroxidative stress and alteration of mitochondrial complex III and IV proteins in aged WT mice, although hepatic ATP levels seems to be unchanged. In contrast, the aging-related nitroxidative changes were very low in aged Cyp2e1-null mice. These results suggest that CYP2E1 is important in causing aging-dependent hepatic steatosis, apoptosis and fibrosis possibly through increasing nitroxidative stress and that CYP2E1 could be a potential target for translational research in preventing aging-related liver disease.

Histopathological, oxidative damage, biochemical, and genotoxicity alterations in hepatic rats exposed to deltamethrin: modulatory effects of garlic (Allium sativum).

Deltamethrin is a pesticide widely used as a synthetic pyrethroid. The aim of this study was undertaken to investigate the effects of deltamethrin to induce oxidative stress and changes in biochemical parameters, hepatotoxicity and genotoxicity in female rats following a short-term (30 days) oral exposure and attenuation of these effects by Allium sativum extract. Indeed, Allium sativum is known to be a good antioxidant food resource which helps destroy free radical particles. Our results showed that deltamethrin treatment caused an increase in liver enzyme activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH); and hepatic lipid peroxidation (LPO) level. However, it induced a decrease in activities of hepatic catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) (p < 0.01). Allium sativum extract normalized significantly (p < 0.01) the mentioned parameters in deltamethrin-treated rats. For genotoxic evaluation, deltamethrin treatment showed a significant increase in frequencies of micronucleus in bone-marrow cells. Micronucleus formation is an indicator of chromosomal damage which has been increasingly used to detect the genotoxic potential of environmental pests. The present study showed that Allium sativum diminished the adverse effects induced by this synthetic pyrethroid insecticide.

Analyses d’articles

Kamebakaurin (KA) is an ent-kaurane diterpenoid known to have anti-inflammatory potential. In the current study, we investigated whether pretreatment with KA could ameliorate acetaminophen (APAP)-induced hepatotoxicity by inhibiting the anti-inflammatory response in mice.Seven-week-old C57BL/6J mice were orally administered KA or olive oil emulsion for seven days. Twenty-four hours after the last KA or olive oil administration, the mice were intraperitoneally injected with 400 mg/kg APAP or saline under feed deprived condition. The mice from each group were euthanized and bled for plasma analysis 24 h after the injection.APAP increased plasma levels of hepatic injury markers (i.e., alanine aminotransferase and aspartate aminotransferase), lipid peroxidation, and pro-inflammatory cytokines. Pretreatment with KA reduced the magnitude of APAP-induced increases in plasma levels of hepatic injury markers, lipid peroxidation, and inflammatory response. In addition, KA exhibited antioxidant capacity in a dose-dependent manner, with slight reactive oxygen species scavenging activity.Our results indicate that KA has the ability to protect the liver from APAP-induced hepatotoxicity, presumably by both inhibiting the inflammatory response and oxidative stress.

Biochemical Effect of Cranberry Extract on Experimental Toxicity with Iron

The present study was aimed to evaluate the protective effective role of cranberry extract against ironoverloadinduced hepatic toxicity in rats. By administration of iron sulfate (30 mg/kg body weight)orally for 21 days, led to significantly increases in the levels of hemoglobin, glucose, lipid profile,plasma and hepatic lipid peroxidation, iron and transferrin. Also, the oral administration of iron sulfateshowed a significant decrease in the levels of plasma and liver enzymatic and non-enzymaticantioxidants. Administration of cranberry extract at different doses (75 and 150 mg/kg body weight)significantly restore the levels of plasma and hepatic markers, lipid profile, lipid peroxidation as well asincreased the levels of plasma and hepatic antioxidants with normal plasma iron and transferrinconcentration in blood. Cranberry extract at a dose of 150 mg/kg body weight exhibits significantprotection on hepatic antioxidants more pronounced than both cranberry 75 mg/kg.b.w. and vitamin C.On the other hand, the results clearly suggest that the cranberry extract may be effective in enhances theprotection of liver toxicity by its free radical scavenging effect and antioxidant activity

Paraoxonase-1 (PON1) inhibition by tienilic acid produces hepatic injury: Antioxidant protection by fennel extract and whey protein concentrate

This study evaluated the effect of whey protein concentrate (WPC) or fennel seed extract (FSE) on paraoxonase-1 activity (PON1) and oxidative stress in liver of tienilic acid (TA) treated rats. Six groups of rats were treated for six weeks as follows: control; WPC (0.5g/kg/day); FSE (200mg/ kg/day); TA (1g/kg/twice a week); TA (1g/kg/twice a week) plus WPC (0.5g/kg/day); TA (1g/kg/twice a week) plus FSE (200mg/kg/day). TA administration significantly increased ALT and AST besides to total- and direct bilirubin levels. Also, serum tumor necrosis factor-α and nitric oxide levels were significantly increased. Furthermore, serum PON1, and hepatic reduced glutathione, glutathione-S-transferase and Na+/K+-ATPase values were diminished matched with a significant rise in the level of hepatic lipid peroxidation. Also, triglycerides, total- and LDL-cholesterol levels were significantly elevated while HDL-cholesterol was unchanged. The administration of either WPC or FSE to TA—treated animals significantly protected the liver against the injurious effects of tienilic acid. This appeared from the improvement of hepatic functions, atherogenic markers, Na+/K+ ATPase activity, endogenous antioxidants and hepatic lipid peroxidation level; where WPC showed the strongest protection effect. In conclusion, the present study indicated that WPC and FSE improve PON1 activity and attenuate liver dysfunction induced by TA. This may be attributed to the high content of antioxidant compounds in WPC and fennel extract.

Chemical composition and hepatoprotective effects of polyphenols extracted from the stems and leaves of Sphallerocarpus gracilis

The phenolic composition and hepatoprotective effects of phenolic extracts of the stems and leaves of Sphallerocarpus gracilis (PESG) were investigated. The predominant constituents of PESG were found to be luteolin-7-O-glucoside, acacetin-7-O-acetyglycoside and isomers of the latter by HPLC–MS. Oral administration of PESG (200 and 400 mg/kg/bw) to mice significantly reduced the effects of CCl4 toxicity on serum markers of hepatic damage, including serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, triacylglycerols, total bilirubin and alkaline phosphatase. PESG treatment also increased the hepatic levels of the antioxidant glutathione and the antioxidant enzymes of superoxide dismutase and catalase and ameliorated the elevated level of hepatic lipid peroxidation induced by CCl4 treatment of the mice. Moreover, in vitro experiments showed that PESG reduced BRL hepatocyte apoptosis and the level of damage to these cells caused by CCl4 treatment. These findings indicate that PESG could be developed as a functional food for therapeutic purpose and for prevention of hepatic injury.

Alteration of hepatic anti-oxidant systems by 4-nonylphenol, a metabolite of alkylphenol polyethoxylate detergents, in Far Eastern catfish Silurus asotus.

ObjectivesThis study aimed to estimate the effects of 4-nonylphenol (NP), a ubiquitously present surfactant in aquatic environments, on the anti-oxidant systems of the liver in the Far Eastern catfish Silurus asotus.MethodsChanges in biochemical parameters involved in glutathione (GSH)-related and other anti-oxidant systems were analyzed following 4 weeks of 4-NP administration (0.1 and 1.0 mg/kg diet) via a formulated diet to catfish.Results4-NP exposure induced an elevation in hepatic lipid peroxide levels and an accompanying decrease in reduced state GSH after 2 weeks, suggesting pro-oxidant effects of the chemical in catfish. This oxidative stress was associated with an inhibition of the GSH-utilizing enzyme glutathione peroxidase at the same time point. This inhibition was restored after 4 weeks. The activities of other anti-oxidant enzymes, i.e., glutathione reductase, superoxide dismutase and catalase were increased after 4 weeks. These enzyme increases occurred more strongly at the higher 4-NP concentration (1.0 mg/kg diet).Conclusions4-NP given to catfish at 0.1 to 1.0 mg/kg diet, concentrations relevant to environmental levels, depletes the endogenous anti-oxidant molecule GSH and temporarily inhibits GSH-related anti-oxidant enzymes. Such declines in anti-oxidant capacity and elevated oxidative stress seem to be compensated eventually by subsequent activation of various anti-oxidant enzyme systems.

Hawthorn ethanolic extracts with triterpenoids and flavonoids exert hepatoprotective effects and suppress the hypercholesterolemia-induced oxidative stress in rats.

The current study was aimed to determine the bioactive constituents and biological effects of the Crataegus monogyna ethanolic extracts from bark, leaves and berries on hypercholesterolemia. Oleanolic acid, ursolic acid, quercetin and lupeol concentrations were quantified by HPLC. Total phenol content and radical scavenging activity of extracts were also measured. The hypocholesterolemic, antioxidant, and hepatoprotective effects of the extracts were examined in hypercholesterolemic rats and compared with orlistat. The highest phenol content, oleanolic acid, quercetin and lupeol levels and free radical scavenging potency were found in the bark extract, and the highest ursolic acid level was found in the berries extract. Orlistat and extracts significantly (P<0.05) lowered the hypercholesterolemia-increased serum level of hepatic enzymes and lipid peroxidation level. Hawthorn's extracts protected from hepatic thiol depletion and improved the lipid profile and hepatic damages. Data suggested that hawthorn's extracts are able to protect from hypercholesterolemia-induced oxidative stress and hepatic injuries. Moreover, the hypocholesterolemic effect of extracts was found comparable to orlistat.

Ketone Body Therapy Protects From Lipotoxicity and Acute Liver Failure Upon Pparα Deficiency.

Acute liver failure (ALF) is a severe and rapid liver injury, often occurring without any preexisting liver disease, which may precipitate multiorgan failure and death. ALF is often associated with impaired β-oxidation and increased oxidative stress (OS), characterized by elevated levels of hepatic reactive oxygen species (ROS) and lipid peroxidation (LPO) products. Peroxisome proliferator-activated receptor (PPAR)α has been shown to confer hepatoprotection in acute and chronic liver injury, at least in part, related to its ability to control peroxisomal and mitochondrial β-oxidation. To study the pathophysiological role of PPARα in hepatic response to high OS, we induced a pronounced LPO by treating wild-type and Pparα-deficient mice with high doses of fish oil (FO), containing n-3 polyunsaturated fatty acids. FO feeding of Pparα-deficient mice, in contrast to control sunflower oil, surprisingly induced coma and death due to ALF as indicated by elevated serum alanine aminotransferase, aspartate aminotransferase, ammonia, and a liver-specific increase of ROS and LPO-derived malondialdehyde. Reconstitution of PPARα specifically in the liver using adeno-associated serotype 8 virus-PPARα in Pparα-deficient mice restored β-oxidation and ketogenesis and protected mice from FO-induced lipotoxicity and death. Interestingly, administration of the ketone body β-hydroxybutyrate prevented FO-induced ALF in Pparα-deficient mice, and normalized liver ROS and malondialdehyde levels. Therefore, PPARα protects the liver from FO-induced OS through its regulatory actions on ketone body levels. β-Hydroxybutyrate treatment could thus be an option to prevent LPO-induced liver damage.

Honey has a protective effect against chlorpyrifos-induced toxicity on lipid peroxidation, diagnostic markers and hepatic histoarchitecture

IntroductionCurrently, there is increasing interest in the identification of natural sources of antioxidants that have minimal side effects and can be used as preventive medicine. In this study, the protective role of honey against oxidative damage and hepatotoxicity induced by sub-chronic exposure to chlorpyrifos (CPF) was investigated. MethodsFemale Wistar rats (n=24) were randomly divided into the following four groups: (1) control, (2) honey-treated (3.0g/kg), (3) CPF-treated (5.4mg/kg) and (4) honey (3.0g/kg)+CPF (5.4mg/kg) treatments. All of the doses were administered daily via oral gavage for 4 weeks. ResultsOral exposure to CPF caused hepato- and nephrotoxicity as indicated by the marked elevation in the serum hepatic marker enzymes (the transaminases and alkaline phosphatase activities), the total bilirubin, total cholesterol, triglycerides, urea, creatinine and hepatic lipid peroxidation levels, whereas the serum total protein level was significantly lower compared with the control. A significant decrease in the body weight gain and an increase in the absolute and relative liver weights were observed in the CPF-treated animals compared with the control. The biochemical alterations observed were accompanied by histopathological changes marked by the appearance of degenerative necrosis, congestion, inflammation and edema in the liver section. However, co-treatment with honey ameliorated the changes in the investigated biochemical parameters and the changes in the body and liver weights as revealed by the inhibition of lipid peroxidation and the improvement observed histopathologically. ConclusionsThe present study suggests that honey has a protective potential for the alleviation of hepatic and renal toxicities induced by CPF.

Chicory (Cichorium intybus L.) root extract regulates the oxidative status and antioxidant gene transcripts in CCl4-induced hepatotoxicity.

The ability of Cichorium intybus root extract (chicory extract) to protect against carbon tetrachloride (CCl4)-induced oxidative stress and hepatotoxicity was evaluated in male rats. The rats were divided into four groups according to treatment: saline (control); chicory extract (100 mg/kg body weight daily, given orally for 2 weeks); CCl4 (1 ml/kg body weight by intraperitoneal injection for 2 consecutive days only); or chicory extract (100 mg/kg body weight daily for 2 weeks) + CCl4 injection on days 16 and 17. The levels of hepatic lipid peroxidation, antioxidants, and molecular biomarkers were estimated twenty-four hours after the last CCl4 injection. Pretreatment with chicory extract significantly reduced CCl4-induced elevation of malondialdehyde levels and nearly normalized levels of glutathione and activity of glutathione S-transferase, glutathione peroxidase (GPx), glutathione reductase, catalase (CAT), paraoxonase-1 (PON1), and arylesterase in the liver. Chicory extract also attenuated CCl4-induced downregulation of hepatic mRNA expression levels of GPx1, CAT and PON1 genes. Results of DNA fragmentation support the ability of chicory extract to ameliorate CCl4-induced liver toxicity. Taken together, our results demonstrate that chicory extract is rich in natural antioxidants and able to attenuate CCl4-induced hepatocellular injury, likely by scavenging reactive free radicals, boosting the endogenous antioxidant defense system, and overexpressing genes encoding antioxidant enzymes.

Geniposide protects against acute alcohol-induced liver injury in mice via up-regulating the expression of the main antioxidant enzymes.

Geniposide (GP) is one of main compounds in Gardenia jasminoides Ellis, with both medicinal and nutritional value. This study was designed to determine, for the first time, how GP from G. jasminoides protects against acute alcohol-induced liver injury, and the underlying mechanisms. Mice were orally administered alcohol (6.0 g/kg body mass) 2 h after intragastric administration of GP and bifendate, every day for 7 continuous days. Six hours after the alcohol was administered, levels of serum alanine/aspartate transaminase (ALT/AST), hepatic lipid peroxidation (LPO), glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), copper- and zinc-containing superoxide dismutase (CuZn-SOD), and catalase (CAT), and mRNA expression of CuZn-SOD and CAT were assayed. The results demonstrated that GP (20.0, 40.0, or 80 mg/kg) significantly reversed the excessive, alcohol-induced elevation in both serum ALT/AST and hepatic LPO levels. Moreover, hepatic GSH, GST, GPx, CuZn-SOD, and CAT levels were all decreased in the alcohol-treated mice, whereas treatment with GP reversed these decreases. Further analysis indicated that hepatic mRNA expression of CuZn-SOD and CAT in the alcohol-treated mice was significantly down-regulated, whereas GP up-regulated such decreases. Taken together, this study shows that GP protects against acute alcohol-induced liver injury via up-regulating the expression of the main antioxidant enzymes, and thus ameliorates alcohol-induced oxidative stress injury in the liver.

Cranberry Extract as a Functional Food in Treatment of Oxidative Stress in Iron- Induced Hepatic Toxicity in Rats

The present study was to evaluate the protective role of cranberry extract against iron-induced hepatic toxicity in rats. Administration of iron sulfate (30 mg/kg body weight) orally for 21 days, led to significantly (p<0.01) increased in the levels of blood hemoglobin, glucose, lipid profile, plasma and hepatic lipid peroxidation, iron and transferrin. Also, oral administration of iron sulfate showed a significant decrease (p<0.01) in the levels of plasma and liver enzymatic and non-enzymatic antioxidants. Administration of cranberry extract at different doses (75 mg/kg and 150 mg/kg body weight) significantly (p<0.01) restore the levels of plasma and hepatic markers, lipid profile, lipid peroxidation levels as well as increased the levels of plasma and hepatic enzymatic antioxidants and non-enzymatic antioxidants with normalize plasma iron and transferrin concentration in blood. Cranberry extract at a dose of 150 mg/kg body weight exhibits significant protection on hepatic more pronounced than both cranberry 75 mg/kg b.w. and vitamin C. In conclusion, the results clearly suggest that the cranberry extract may be effective in enhances the protection of liver toxicity by its free radical scavenging effect and antioxidant activity.

Protective effect of Amaranthus lividus L. on carbon tetrachloride induced hepatotoxicity in rats

Objective: Amaranthus lividus is consumed as popular vegetable in West Black Sea Region of Turkey. In this study, we aimed to evaluate the protective and antioxidant effects of A. lividus on carbon tetrachloride (CCl 4 ) induced oxidative stress and acute liver injury in rats. Methods: Male albino Wistar rats were divided into 7 groups: Normal control, A. lividus control, silymarin control, CCl 4 , A. lividus (250 mg/kg)+CCl 4 , A. lividus (500 mg/kg)+CCl 4 , silymarin+CCl 4 . Rats were orally pretreated with A. lividus (250 and 500 mg/kg) or silymarin (25 mg/kg) daily for 9 days before administration of CCl 4 (1.5 mL/kg, 1:1 in olive oil, i.p.). Results: Pretreatment of rats with A. lividus, significantly prevented the CCl 4 induced elevation in the levels of serum alanine aminotransferase, aspartate aminotransferase, bilirubin and hepatic lipid peroxidation and myeloperoxidase. In addition, pretreatment with A. lividus significantly prevented the CCl 4 induced depletion in the activities of antioxidant enzymes such as catalase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase and glutathione level in liver. It has been observed that the hepatoprotective effect of A. lividus was comparable to that of silymarin, a standard drug. Histopathological evaluation of the liver also revealed that A. lividus at 250 mg/kg dose partially suppressed the CCl 4 induced liver damage in rats. Conclusion: Our results indicated that A. lividus has a protective effect against CCl 4 induced acute hepatotoxicity in rats, and this effect might be related to its antioxidant activity.

Valproate-Induced Liver Injury: Modulation by the Omega-3 Fatty Acid DHA Proposes a Novel Anticonvulsant Regimen

BackgroundThe polyunsaturated, ω-3 fatty acid, docosahexaenoic acid (DHA), claims diverse cytoprotective potentials, although via largely undefined triggers. Thus, we currently first tested the ability of DHA to ameliorate valproate (VPA)-evoked hepatotoxicity, to modulate its anticonvulsant effects, then sought the cellular and molecular basis of such actions. Lastly, we also verified whether DHA may kinetically alter plasma levels/clearance rate of VPA.Methods and ResultsVPA (500 mg/kg orally for 14 days in rats) evoked prominent hepatotoxicity that appeared as a marked rise (2- to 4-fold) in serum hepatic enzymes (γ-glutamyl transferase [γ-GT], alanine aminotransferase [ALT], and alkaline phosphatase [ALP]), increased hepatic lipid peroxide (LPO) and tumor necrosis factor-alpha (TNFα) levels, as well as myeloperoxidase (MPO) activity (3- to 5-fold), lowering of serum albumin (40 %), and depletion of liver reduced-glutathione (GSH, 35 %). Likewise, histopathologic examination revealed hepatocellular degeneration, replacement by inflammatory cells, focal pericentral necrosis, and micro/macrovesicular steatosis. Concurrent treatment with DHA (250 mg/kg) markedly blunted the elevated levels of liver enzymes, lipid peroxides, TNFα, and MPO activity, while raising serum albumin and hepatic GSH levels. DHA also alleviated most of the cytologic insults linked to VPA. Besides, in a pentylenetetrazole (PTZ) mouse convulsion model, DHA (250 mg/kg) markedly increased the latency in convulsion evoked by VPA, beyond their individual responses. Lastly, pharmacokinetic studies revealed that joint DHA administration did not alter serum VPA concentrations.ConclusionsDHA substantially ameliorated liver injury induced by VPA, while also markedly boosted its pharmacologic effects. DHA manipulated definite cellular machinery to curb liver oxidative stress and inflammation, without affecting VPA plasma levels. Collectively, these protective and synergy profiles for DHA propose a superior VPA-drug combination regimen.

Gypenoside attenuates hepatic ischemia/reperfusion injury in mice via anti-oxidative and anti-apoptotic bioactivities.

Gynostemma pentaphyllum is a traditional Chinese medicine that has previously been used for the treatment of chronic inflammation, hyperlipidemia and liver disease. Gypenoside (GP), the predominant component of Gynostemma pentaphyllum, exhibits a therapeutic effect on chronic hepatic injury, fibrosis and fatty liver disease via its anti-inflammatory and anti-oxidant activity. However, the effect of GP on ischemia/reperfusion (I/R)-induced hepatic injury has, to the best of our knowledge, not previously been investigated. In the present study, a hepatic I/R-injury model was successfully established using C57BL/6 mice. In the treatment group, 50 mg/kg GP was administered orally 1 h prior to ischemia. Following hepatic I/R, the levels of hepatic lipid peroxidation and serum alanine aminotransferase increased, while the ratio of hepatic glutathione (GSH):oxidized GSH was reduced, which was effectively attenuated by pretreatment with GP. Furthermore, an increased protein expression of heme oxygenase-1 in the liver tissues of the I/R mice was attenuated by the administration of GP. In addition, the present study indicated that treatment with GP suppressed the I/R-induced increase in the pro-apoptotic protein levels of Bax and cytochrome c and the activity of caspase-3/8, as well as the I/R-induced decrease in the levels of anti-apoptotic protein Bcl-2. In conclusion, the present study indicated that GP effectively protected against I/R-induced hepatic injury via its anti-oxidative and anti-apoptotic bioactivity.

Scopoletin prevents alcohol-induced hepatic lipid accumulation by modulating the AMPK–SREBP pathway in diet-induced obese mice

ObjectiveThis study investigated the effects of scopoletin on alcohol-induced hepatic lipid accumulation in diet-induced obese mice and its mechanism. Material/MethodsAlcohol (25% v/v, 5g/kg body weight) was orally administered once a day for 6 weeks to mice fed with a high-fat diet (35%kcal) with or without scopoletin (0.05%, wt/wt). ResultsScopoletin reduced plasma acetaldehyde, fatty acid, total cholesterol, triglyceride and insulin levels, hepatic lipid and droplets and fasting blood glucose levels that were increased by alcohol. Scopoletin significantly activated hepatic AMPK and inhibited ACC and SREBP-1c and the activities of lipogenic enzymes, such as FAS, PAP and G6PD compared to the alcohol control group. Moreover, scopoletin significantly inhibited hepatic CYP2E1 activity and protein levels but elevated the activities of SOD, CAT, GSH-Px and GST and the levels of GSH compared to the alcohol control group. The hepatic lipid peroxide level was significantly lowered by scopoletin supplementation in alcohol-administered obese mice. ConclusionsTaken together, these results suggested that scopoletin can ameliorate alcohol-induced hepatic lipid accumulation by modulating AMPK–SREBP pathway-mediated lipogenesis in mice fed a high-fat diet.

Protective effect of danhong injection on acute hepatic failure induced by lipopolysaccharide and d-galactosamine in mice.

Acute hepatic failure (AHF), which leads to an extremely high mortality rate, has become the focus of attention in clinic. In this study, Danhong injection (DHI) was investigated to evaluate the preventive and protective effect on AHF induced by lipopolysaccharide (LPS) and D-galactosamine (GalN) in mice. For AHF induction, ICR mice were intraperitoneally injected with D-GalN (700 mg/kg) and LPS (20 μg/kg). DHI was administrated twice, at 12 and 1 h, respectively, before D-GalN/LPS injection. After stimulation with D-GalN/LPS for 1 and 6 h, serum and livers were collected for analysis. We found that mice administrated with DHI displayed a higher survival rate, lower serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), glutathione S-transferase (GST), and tumor necrosis factor (TNF)-α. DHI inhibited the elevations of hepatic lipid peroxidation (malondialdehyde), caspase-8 activity, and mRNA expression levels of inflammatory cytokines (interleukin-1β and interleukin-6) increased by D-GalN/LPS in the liver. Furthermore, liver histopathological analysis indicated that the DHI group showed markedly fewer apoptotic (TUNEL positive) cells and less pathological changes than those in the AHF model group. These results provide a novel insight into the pharmacological actions of DHI as a potential candidate for treating AHF.

Pycnogenol attenuates the symptoms of immune dysfunction through restoring a cellular antioxidant status in low micronutrient-induced immune deficient mice.

BACKGROUND/OBJECTIVESWe investigated the effect of Pycnogenol (Pyc) on survival and immune dysfunction of C57BL/6 mice induced by low micronutrient supplementation.MATERIALS/METHODSFemale C57/BL/6 mice were fed a diet containing 7.5% of the recommended amount of micronutrients for a period of 12 wks (immunological assay) and 18 wks (survival test). For immunological assay, lymphocyte proliferation, cytokine regulation, and hepatic oxidative status were determined.RESLUTSPyc supplementation with 50 and 100 mg·kg-1·bw·d-1 resulted in partial extension of the median survival time. Pyc supplementation led to increased T and B cell response against mitogens and recovery of an abnormal shift of cytokine pattern designated by the decreased secretion of Th1 cytokine and increased secretion of Th2 cytokine. Hepatic vitamin E level was significantly decreased by micronutrient deficiency, in accordance with increased hepatic lipid peroxidation level. However, Pyc supplementation resulted in a dose-dependent reduction of hepatic lipid peroxidation, which may result from restoration of hepatic vitamin E level.CONCLUSIONFindings of this study suggest that Pyc supplementation ameliorates premature death by restoring immune dysfunction, such as increasing lymphocyte proliferation and regulation of cytokine release from helper T cells, which may result from the antioxidative ability of Pyc.

Ameliorative effects of phyllanthin on carbon tetrachloride-induced hepatic oxidative damage in mice

ObjectiveTo evaluate the liver protecting efficacy of phyllanthin, a lignin, isolated from the leaves of Phyllanthus amarus using mice model. MethodsPhyllanthin was orally administered with or without CCl4 for 30 d. Serum levels of hepatic marker enzymes namely alanine transaminase and aspartate transaminase were evaluated. Oxidative stress was ascertained by measuring hepatic lipid peroxidation levels and by estimating non-enzymatic antioxidants such as glutathione, total ascorbic acid, enzymatic antioxidants namely catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione transferase. Histopathological and ultramicroscopic analyses were also carried out. ResultsOral administration of CCl4 caused significant increase in lipid peroxidation. The hepatic levels of both non-enzymatic antioxidants and enzymatic antioxidants were significantly lowered in CCl4-treated mice as compared to control. Treatment with phyllanthin significantly mitigated these changes in the CCl4-treated mice. Histopathological and ultramicroscopic studies correlated well with the biochemical findings, as phyllanthin treatment reversed the alterations induced by the toxin and the subcellular features of phyllanthin treated mice were similar to those present in the normal mouse liver. ConclusionsThis study reports the in vivo anti-hepatotoxic potential of this isolated molecule phyllanthin, which may be responsible for the liver protecting property of Phyllanthus amarus.