1-1-diphenyl-2-picrylhydrazyl and Liver-Diseases

Oxidative stress is thought to be a key risk factor in the development of hepatic diseases. Blocking or retarding the reactions of oxidation and the inflammatory process by antioxidants could be a promising therapeutic intervention for prevention or treatment of liver injuries. Oligonol is a low molecular weight polyphenol containing catechin-type monomers and oligomers derived from lychee fruit. In this study, we investigated the anti-inflammatory effect of oligonol on carbon tetrachloride- (CCl4-) induced acute hepatic injury in rats. Oral administration of oligonol (10 or 50 mg/kg) reduced CCl4-induced abnormalities in liver histology and serum AST and serum ALT levels. Oligonol treatment attenuated the CCl4-induced production of inflammatory mediators, including TNF-α, IL-1β, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA levels. Western blot analysis showed that oligonol suppressed proinflammatory nuclear factor-kappa B (NF-κB) p65 activation, phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinases (MAPKs) as well as Akt. Oligonol exhibited strong antioxidative activity in vitro and in vivo, and hepatoprotective activity against t-butyl hydroperoxide-induced HepG2 cells. Taken together, oligonol showed antioxidative and anti-inflammatory effects in CCl4-intoxicated rats by inhibiting oxidative stress and NF-κB activation via blockade of the activation of upstream kinases including MAPKs and Akt.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Biphenyl Compounds; Carbon Tetrachloride; Catechin; Cell Nucleus; Cyclooxygenase 2; Enzyme Activation; Ferrous Compounds; Gene Expression Regulation; Hep G2 Cells; Humans; Hydrogen Peroxide; Interleukin-1beta; Lipid Peroxidation; Liver; Liver Diseases; Malondialdehyde; MAP Kinase Signaling System; NF-kappa B; Nitric Oxide Synthase Type II; Phenols; Picrates; Protein Transport; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; tert-Butylhydroperoxide; Tumor Necrosis Factor-alpha

In view of the contribution of iron deposition in the oxidative pathologic process of liver disease, the potential of 70% methanolic extract of C. cajan leaf (CLME) towards antioxidative protection against iron-overload-induced liver damage in mice has been investigated. DPPH radical scavenging and protection of Fenton reaction induced DNA damage was conducted in vitro. Post oral administration of CLME to iron overloaded mice, the levels of antioxidant and serum enzymes, hepatic iron, serum ferritin, lipid peroxidation, and protein carbonyl and hydroxyproline contents were measured, in comparison to deferasirox treated mice. Oral treatment of the plant extract effectively lowered the elevated levels of liver iron, lipid peroxidation, protein carbonyl and hydroxyproline. There was notable increment in the dropped levels of hepatic antioxidants. The dosage of the plant extract not only made the levels of serum enzymes approach normal value, but also counteracted the overwhelmed serum ferritin level. The in vitro studies indicated potential antioxidant activity of CLME. The histopathological observations also substantiated the ameliorative function of the plant extract. Accordingly, it is suggested that Cajanus cajan leaf can be a useful herbal remedy to suppress oxidative damage caused by iron overload.

Topics: Animals; Antioxidants; Biomarkers; Biphenyl Compounds; Cajanus; Chromatography, High Pressure Liquid; DNA Damage; Dose-Response Relationship, Drug; Free Radical Scavengers; Iron Overload; Liver; Liver Diseases; Mice; Oxidative Stress; Phytotherapy; Picrates; Plant Extracts; Plant Leaves; Protective Agents; Reference Standards

Water-soluble polysaccharides were isolated from the brown alga Hizikia fusiformis and separated using hydrophobic chromatography on an ME-1 resin column. Three major polysaccharide fractions, FG, GM-1 and GM-2, were analyzed by high-performance liquid chromatography, Fourier-transform infrared and (13)C nuclear magnetic resonance spectroscopy. These three fractions showed free radical scavenging activity against hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl radical in vitro. Among these three fractions, GM-2 had the best free radical scavenging activity. Thus, only GM-2 was used in the acute oxidative stress experiments in the CCl₄-induced liver injury model. GM-2 also protected against oxidative injury induced by CCl₄in vivo.

Topics: Animals; Antioxidants; Biomarkers; Biphenyl Compounds; Carbon Tetrachloride; Free Radical Scavengers; Hydroxyl Radical; Liver Diseases; Mice; Phaeophyceae; Picrates; Polysaccharides; Protective Agents; Solubility; Spectroscopy, Fourier Transform Infrared; Water

The aim of the study was to investigate the in vitro antioxidant properties Moringa oleifera Lam. (MO) extracts and its curative role in acetaminophen (APAP)-induced toxic liver injury in rats caused by oxidative damage. The total phenolic content and antioxidant properties of hydroethanolic extracts of different MO edible parts were investigated by employing an established in vitro biological assay. In the antihepatotoxic study, either flowers or leaves extract (200 mg/kg or 400 mg/kg, i.p) were administered an hour after APAP administration, respectively. N-Acetylcysteine was used as the positive control against APAP-induced hepatotoxicity. The levels of liver markers such as alanine aminotransferase (ALT) and the levels of oxidative damage markers including malondialdehyde (MDA), 4-hydroxynonenal (4-HNE) protein adduct, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were analysed and compared between experimental groups. Among MO edible parts the flower extracts contain the highest total phenolic content and antioxidant capacity, followed by leaves extract. The oxidative marker MDA, as well as 4-HNE protein adduct levels were elevated and GSH, SOD and CAT were significantly decreased in groups treated with hepatotoxin. The biochemical liver tissue oxidative markers measured in the rats treated with MO flowers and leaves hydroethanolic extracts showed a significant (p < 0.05) reduction in the severity of the liver damage. The results of this study strongly indicate the therapeutic properties of MO hydroethanolic extracts against acute liver injury and thereby scientifically support its traditional use.

Topics: Acetaminophen; Aldehydes; Animals; Antioxidants; Biomarkers; Biphenyl Compounds; Ethanol; Flowers; Fluorescence Recovery After Photobleaching; Free Radical Scavengers; Glutathione; Liver; Liver Diseases; Liver Function Tests; Male; Malondialdehyde; Moringa oleifera; Oxidative Stress; Phenols; Phytotherapy; Picrates; Plant Extracts; Rats; Rats, Sprague-Dawley; Water

Ischemia/reperfusion (I/R) injury is characterized by significant oxidative stress, which induces characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. The aim of this study was to evaluate the protective effect of dihydrolipoyl histidinate zinc complex (DHLHZn) on oxidative damage after severe hepatic I/R injury.. Thirty male Wistar rats were subjected to 45 min of hepatic ischemia by clamping of the hepatic artery and portal vein, followed by a 6-h reperfusion period. DHLHZn (10 mg/kg) (I/R + DHLHZn group) or saline (I/R group) was administered intraperitoneally twice, 30 min before ischemia and at the beginning of the reperfusion. Sham-operated animals (sham group) received equal amounts of saline. The rats were killed at the end of the reperfusion period. Serum levels of aspartate aminotransferase and alanine aminotransferase were determined, and histological examination and oxidative stress were evaluated in liver tissues. In addition, antimycin A-stimulated RAW264.7 cells (murine macrophage-like cells) were treated with DHLHZn to estimate its antioxidant effect.. Serum aspartate aminotransferase and alanine aminotransferase levels were increased in the I/R group, but these increases were significantly inhibited in the I/R + DHLHZn group. Similarly, liver tissue damage observed in the I/R group was attenuated in the I/R + DHLHZn group. Cells treated in vitro with both DHLHZn and antimycin A showed reduced reactive oxygen species activity compared to cells treated with antimycin A alone.. The new antioxidant DHLHZn may have potential for therapeutic application in liver I/R injury, although this is a limited animal study.

Topics: Alanine Transaminase; Animals; Antimycin A; Antioxidants; Aspartate Aminotransferases; Biomarkers; Biphenyl Compounds; Cell Line; Disease Models, Animal; Dose-Response Relationship, Drug; Histidine; Liver; Liver Diseases; Male; Malondialdehyde; Mice; Oxidative Stress; Picrates; Rats; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury; Thioctic Acid; Time Factors

Saponins are valuable principles found in various herbal medicine with pharmaceutical, cosmetical and nutraceutical merits. In this study, we evaluated the protective role of saponin fraction (Cl-SF), prepared from Codonopsis lanceolata, an ethnopharmacologically famous plant in Korea, China and Japan, on water immersion stress-induced liver damage and radical generation. Cl-SF clearly decreased the up-regulated levels of serum glutamate-oxalacetate transaminase and glutamate-pyruvate-transaminase induced by water-immersed stress conditions. Furthermore, Cl-SF seemed to block the stress-induced radicals. Thus, Griess and DPPH assays revealed that Cl-SF significantly suppressed both radical generation in sodium nitroprusside-treated RAW264.7 cells and nitric oxide production in LPS-treated RAW264.7 cells. Therefore, these results suggest that Cl-SF may be considered as a promising stress-regulatory principle with radical scavenging actions.

Topics: Animals; Biphenyl Compounds; Cell Line; Cell Proliferation; Cell Survival; Codonopsis; Disease Models, Animal; Free Radical Scavengers; Immersion; Liver Diseases; Male; Mice; Mice, Inbred ICR; Nitric Oxide; Picrates; Reactive Oxygen Species; Saponins; Stress, Psychological

Hibiscus hispidissimus Griff. is used in tribal medicine of Kerala, the southern most state of India, to treat liver diseases. In the present study, the effect of the ethanolic extract of Hibiscus hispidissimus whole plant on paracetamol (PCM)-induced and carbon tetrachloride (CCl4)-induced liver damage in healthy Wistar albino rats was studied. The results showed that significant hepatoprotective effects were obtained against liver damage induced by PCM and CCl4 as evidenced by decreased levels of serum enzymes, glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SAKP), serum bilirubin (SB) and an almost normal histological architecture of the liver of the treated groups compared to the toxin controls. The extract also showed significant antilipid peroxidant effects in vitro, besides exhibiting significant activity in quenching 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical, indicating its potent antioxidant effects.

Topics: Acetaminophen; Animals; Biphenyl Compounds; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Ethanol; Free Radical Scavengers; Hibiscus; Lipid Peroxidation; Liver Diseases; Male; Picrates; Plant Extracts; Rats; Rats, Wistar

The antioxidant activity and hepatoprotective potential of Cirsium setidens Nakai, a widely used medicinal plant, were investigated. The n-butanol (n-BuOH) fraction of leaves and roots of C. setidens had a higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity than the other soluble fractions. The n-BuOH fraction of roots of C. setidens had a significant hepatoprotective activity at a dose of 500 mg/kg compared to that of a standard agent. The biochemical results were confirmed by histological observations indicating that C. setidens extract decreased ballooning degeneration in response to CCl(4) treatment. The n-BuOH fraction reduced CCl(4)-induced liver injury in rats, and transcript levels of genes encoding antioxidant enzymes such as glutathione peroxidase 1 (GPO1), glutathione peroxidase 3 (GPO3) and superoxide dismutase (SOD1) were elevated in the livers of rats treated with this fraction (500 mg/kg). Based on these results, we suggest that the C. setidens extract has hepatoprotective effect related to its antioxidant activity.

Topics: Animals; Antioxidants; Biphenyl Compounds; Carbon Tetrachloride Poisoning; Cirsium; DNA; Ethanol; Free Radical Scavengers; Hydrazines; Liver; Liver Diseases; Olive Oil; Picrates; Plant Extracts; Plant Oils; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction

Common sage (Salvia officinalis L., Lamiaceae) is an aromatic and medicinal plant well known for its antioxidant properties. Some in vivo studies have shown the biological antioxidant effects of sage. However, the intracellular antioxidant mechanisms of action are still poorly understood. In this study, we evaluated the cytoprotective effects of two sage extracts (a water and a methanolic extract) against tert-butyl hydroperoxide (t-BHP)-induced toxicity in HepG2 cells. The most abundant phenolic compounds present in the extracts were rosmarinic acid and luteolin-7-glucoside. Both extracts, when co-incubated with the toxicant, protected significantly HepG2 cells against cell death. The methanolic extract, with a higher content of phenolic compounds than the water extract, conferred better protection in this in vitro model of oxidative stress with liver cells. Both extracts, tested in a concentration that protects 80% against cell death (IC(80)), significantly prevented t-BHP-induced lipid peroxidation and GSH depletion, but not DNA damage assessed by the comet assay. The ability of sage extracts to reduce t-BHP-induced GSH depletion by 62% was probably the most relevant contributor to the observed cytoprotection. A good correlation between the above cellular effects of sage and the effects of their main phenolic compounds was found. When incubated alone for 5h, sage extracts induced an increase in basal GSH levels of HepG2 cells, which indicates an improvement of the antioxidant potential of the cells. Compounds present in sage extracts other than phenolics may also contribute to this latter effect. Based in these results, it would be of interest to investigate whether sage has protective effects in suitable in vivo models of liver diseases, where it is known that oxidative stress is involved.

Topics: Biphenyl Compounds; Cell Death; Cell Line, Tumor; Chemical and Drug Induced Liver Injury; Comet Assay; DNA Damage; Dose-Response Relationship, Drug; Free Radical Scavengers; Glutathione; Humans; Hydrazines; Liver; Liver Diseases; Methanol; Oxidative Stress; Picrates; Plant Extracts; Salvia officinalis; Superoxides; tert-Butylhydroperoxide; Thiobarbituric Acid Reactive Substances; Water

The hepatoprotective activities of total flavonoids of Laggera alata (TFLA) were evaluated by carbon tetrachloride (CCl(4))-induced injury in primary cultured neonatal rat hepatocytes and in rats with hepatic damage. In vitro, TFLA at a concentration range of 1-100 microg/ml improved cell viability and inhibited cellular leakage of two enzymes, hepatocyte aspartate aminotransferase (AST) and alanine aminotransferase (ALT), caused by CCl(4). In vivo, oral treatment with TFLA at doses of 50, 100, and 200 mg/kg significantly reduced the levels of AST, ALT, total protein, and albumin in serum and the hydroxyproline and sialic acid levels in liver. Histopathological examinations revealed that liver damage were improved when treated with TFLA. Meanwhile, 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide radicals scavenging activities of TFLA were also determinated. To understand the exact components of TFLA responsible for the hepatoprotective effect, nine flavonoid compounds were isolated and identified from TFLA. In conclusion, the present investigation was the first to verify the hepatoprotective effect of L. alata in vitro and in vivo. The hepatoprotective action of TFLA is likely related to its potent antioxidative and anti-inflammatory activity. Neutralizing reactive oxygen species by nonenzymatic mechanisms and enhancing the activity of original natural hepatic-antioxidant enzymes may be the main mechanisms of TFLA against CCl(4)-induced injury.

Topics: Alanine Transaminase; Analysis of Variance; Animals; Aspartate Aminotransferases; Asteraceae; Biphenyl Compounds; Carbon Tetrachloride; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Flavonoids; Hepatocytes; Histocytochemistry; Hydrazines; Liver Diseases; Picrates; Rats; Superoxides

We evaluated the antioxidative activity of anthocyanins from an extract of the tuber of purple sweet potato (PSP) (Ipomoea batatas cultivar Ayamurasaki). Anthocyanins from PSP showed stronger 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity than anthocyanins from red cabbage, grape skin, elderberry, or purple corn, and eight major components of the anthocyanins from PSP showed higher levels of activity than ascorbic acid. In PSP anthocyanin-injected rats and PSP beverage-administered volunteers, DPPH radical-scavenging activity in the urine increased. The elevation of plasma transaminase activities induced by carbon tetrachloride was depressed in rats administered PSP anthocyanin solution. Two components, cyanidin 3-O-(2-O-(6-O-(E)-caffeoyl-beta-D-glucopyranocyl)-beta-D-glucopyranoide)-5-O-beta-D-glucopyranoside and peonidin 3-O-(2-O-(6-O-(E)-caffeoyl-beta-D-glucopyranocyl)-beta-D-glucopyranoide)-5-O-beta-D-glucopyranoside, which were detected in the plasma, protected low density lipoprotein from oxidation at a physiological concentration. These results indicate that PSP anthocyanins have antioxidative activity in vivo as well as in vitro.

Topics: Adult; Animals; Anthocyanins; Antioxidants; Biphenyl Compounds; Cholesterol, LDL; Female; Free Radical Scavengers; Humans; Ipomoea batatas; Liver Diseases; Male; Middle Aged; Oxidation-Reduction; Picrates; Rats; Rats, Sprague-Dawley

Antrodia camphorata (A. camphorata) is well-known in Taiwan as a traditional Chinese medicine. The purpose of this study was to evaluate the ability of A. camphorata extracts to protect against oxidative stress in vitro and against carbon tetrachloride (CCl(4))-induced hepatic injury in vivo. An extract of A. camphorata inhibited nonenzymatic iron-induced lipid peroxidation in rat brain homogenates with an IC(50) value about 3.1 mg/mL. It also scavenged the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). The dose of the A. camphorata extract resulting in a decrease of 0.20 in the absorbance of DPPH was about 31 +/- 0.7 microg/mL. Furthermore, an A. camphorata extract dose-dependently (250-1250 mg/kg) ameliorated the increase in plasma aspartate aminotransferase (GOT) and alanine aminotransferase (GPT) levels caused by chronic repeated CCl(4) intoxication in mice. Moreover, A. camphorata extract significantly improved the CCl(4)-induced increase in hepatic glutathione peroxidase, reductase, and CCl(4)-induced decrease in superoxide dismutase activities. It also restored the decrement in the glutathione content and catalase activity of hepatic tissues in CCl(4)-intoxicated mice. Furthermore, it also dose-dependently inhibited the formation of lipid peroxidative products during CCl(4) treatment. Histopathological changes of hepatic lesions induced by CCl(4) were significantly ameliorated by treatment with an A. camphorata extract in a dose-dependent manner. These results suggest that A. camphorata extract exerts effective protection against chronic chemical-induced hepatic injury in vivo, by mediating antioxidative and free radical scavenging activities.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Basidiomycota; Biphenyl Compounds; Brain; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Free Radical Scavengers; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Lipid Peroxidation; Liver; Liver Diseases; Male; Medicine, Chinese Traditional; Mice; Mice, Inbred ICR; Picrates; Rats; Rats, Wistar; Superoxide Dismutase

The antioxidant action of medicinal herbs used in Ghana for treating various ailments was evaluated in vitro and in vivo. Five plants, Desmodium adscendens, Indigofera arrecta, Trema occidentalis, Caparis erythrocarpus, and Thonningia sanguinea were tested for their free radical scavenging action by their interaction with 1,1-diphenyl-2-picrylhydrazyl (DPPH). Of these five plants, only Thonningia sanguinea was found to scavenge the DPPH radical. Lipid peroxidation in liver microsomes induced by H2O2 was also inhibited by T. sanguinea. The hepatoprotective effect of T. sanguinea was studied on acute hepatitis induced in rats by a single dose of galactosamine (GalN, 400 mg/kg, IP) and in mice by carbon tetrachloride (CCl4, 25 microl/kg, IP). GalN induced hepatotoxicity in rats as evidenced by an increase in alanine aminotransferase (ALT) and glutathione (GSH) S-transferase activities in serum was significantly inhibited when T. sanguinea extract (5 ml/kg, IP) was given to rats 12 hr and 1 hr before GalN treatment. The activity of liver microsomal GSH S-transferase, which is known to be activated by oxidative stress, was increased by the GaIN treatment and this increase was blocked by T. sanguinea pretreatment. Similarly, T. sanguinea pretreatment also inhibited CCl4-induced hepatotoxicity in mice. These data indicate that T. sanguinea is a potent antioxidant and can offer protection against GalN- or CCl4-induced hepatotoxicity.

Topics: Alanine Transaminase; Aniline Hydroxylase; Animals; Antioxidants; Aspartate Aminotransferases; Bepridil; Biphenyl Compounds; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Free Radical Scavengers; Free Radicals; Galactosamine; Ghana; Glutathione Transferase; Lipid Peroxidation; Liver; Liver Diseases; Male; Mice; Microsomes, Liver; Picrates; Plant Extracts; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Thiobarbituric Acid Reactive Substances