ascorbic-acid and Carbon-Tetrachloride-Poisoning

Brown algae are well known as a source of biologically active compounds, especially those having antioxidant activities, such as phlorotannins. In this study we examined the antioxidant activities of crude phlorotannins extracts (CPEs) obtained from Sargassum hemiphyllum (SH) and fractionated according to the molecular weights. When CPEs were administrated at a dose of 30 mg/kg to Kunming mice pre-treated with carbon tetrachloride (CCl4), the levels of oxidative stress indicators in the liver, kidney and brain were significantly reduced in vivo. All the components of various molecular weight fractions of CPEs exhibited greater scavenging capacities in clearing hydroxyl free radical and superoxide anion than the positive controls gallic acid, vitamin C and vitamin E. Particularly, the components greater than 30 kD obtained from ethyl acetate phase showed the highest antioxidant capacities. These results indicated that SH is a potential source for extracting phlorotannins, the algal antioxidant compounds.

Topics: Animals; Antioxidants; Ascorbic Acid; Brain; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Chemical Fractionation; Gallic Acid; Hydroxyl Radical; Kidney; Liquid-Liquid Extraction; Liver; Male; Mice; Mice, Inbred Strains; Oxidation-Reduction; Oxidative Stress; Phaeophyceae; Sargassum; Superoxides; Tannins; Vitamin E

Carbon tetrachloride (CCl₄) is frequently used as a chemical inducer of tissue damage. Their effects on mouse peritoneal macrophages and also in peripheral blood lymphocytes are still unknown.. Therefore we tried to focus on intracellular oxidative stress produced by CCl₄ in mouse macrophage and lymphocyte cells.. Intraperitoneal administration of CCl₄ induces intracellular superoxide anions production in mouse macrophages and peripheral blood lymphocytes and leads a subsequent lipid peroxidation and protein oxidation. N-acetyl cystein (NAC) and vitamin C were administered intraperitoneally at a dose of 150 mg/kg and their effect on demodulating the oxidative stress is also checked.. Several in vitro approaches have already been established as a free radical scavenging models, but this free radical screening models is not always correlated with the in vivo screening models. NAC and vitamin C were administered intraperitoneally and significant reduction of the oxidative stress in term of scavenging of toxic superoxide anion observed in both the macrophages and lymphocytes.. Therefore we are hopeful that our work will light a new insight into the screening of in vivo free radical scavenging model for evaluating anti-inflammatory compounds.

Topics: Acetylcysteine; Animals; Ascorbic Acid; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Free Radical Scavengers; Lipid Peroxidation; Lymphocytes; Macrophages, Peritoneal; Mice; Oxidative Stress; Superoxides

We have previously reported that radon inhalation activates anti-oxidative functions and inhibits carbon tetrachloride (CCl(4))-induced hepatopathy. It has also been reported that antioxidant vitamins can inhibit CCl(4)-induced hepatopathy. In the current study, we examined the comparative efficacy of treatment with radon, ascorbic acid and α-tocopherol on CCl(4)-induced hepatopathy. Mice were subjected to intraperitoneal injection of CCl(4) after inhaling approximately 1000 or 2000 Bq/m(3) radon for 24 h, or immediately after intraperitoneal injection of ascorbic acid (100, 300, or 500 mg/kg bodyweight) or α-tocopherol (100, 300, or 500 mg/kg bodyweight). We estimated the inhibitory effects on CCl(4)-induced hepatopathy based on hepatic function-associated parameters, oxidative damage-associated parameters and histological changes. The results revealed that the therapeutic effects of radon inhalation were almost equivalent to treatment with ascorbic acid at a dose of 500 mg/kg or α-tocopherol at a dose of 300 mg/kg. The activities of superoxide dismutase, catalase, and glutathione peroxidase in the liver were significantly higher in mice exposed to radon than in mice treated with CCl(4) alone. These findings suggest that radon inhalation has an anti-oxidative effect against CCl(4)-induced hepatopathy similar to the anti-oxidative effects of ascorbic acid or α-tocopherol due to the induction of anti-oxidative functions.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Female; Mice; Mice, Inbred ICR; Radon; Reactive Oxygen Species; Treatment Outcome; Vitamins

The genetic deletion of the senescence marker protein 30 (SMP30) gene results in ascorbate deficiency and the premature aging processes in mice. Apparent liver injury of SMP30(-/-) mice was less severe than those of wild type (WT) mice, upon chronic CCl(4) injection. The purpose of this study was to investigate the pathophysiology underlying the mild CCl(4) toxicity in SMP30(-/-) mice. Along with the lower level of serum alanine aminotransferase, the livers of SMP30(-/-) mice revealed a lesser glycogen depletion, a decrease in c-Jun N-terminal kinase (JNK)-mediated inflammatory signaling in parallel with tumor necrosis factor-alpha and interleukin-1 beta, inducible nitric oxide synthase and glutathione peroxidase, and the lower lipid peroxidation as compared to those of WT mice. CCl(4)-induced proliferation, measured by the expression of proliferating cell nuclear antigen, was low in SMP30(-/-) mice as compared with that of WT mice whereas the levels of p21 and Bax were comparable to those of the CCl(4)-treated WT mice. Moreover, CCl(4) toxicity in ascorbate-fed SMP30(-/-) mice was comparable to that of the CCl(4)-alone treated WT mice, accompanied by an increase in the above mentioned factors. Conversely, ascorbate partly compensated for the CCl(4)-induced oxidative stress in WT mice, indicating that sufficient ascorbate may be required for an antioxidant function under severe levels of oxidative stress. Our data suggest that the restoration of ascorbate-deficiency reverses a sluggish immune system into an activated condition by an increase in JNK-mediated inflammation and free radical cascade; thus leading to accelerated hepatic damage in SMP30(-/-) mice.

Topics: Animals; Antioxidants; Ascorbic Acid; Calcium-Binding Proteins; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Inflammation Mediators; Intracellular Signaling Peptides and Proteins; JNK Mitogen-Activated Protein Kinases; Liver; Mice; Mice, Inbred Strains; Oxidative Stress; Tumor Necrosis Factor-alpha; Up-Regulation

This inventory evaluates toxicological effects and hepatoprotective potential of Clerodendron glandulosum.Coleb (CG) aqueous extract. Acute and subchronic toxicity tests were performed using Swiss albino mice as per the guideline of Organisation for Economic Cooperation and Development (OECD). Also, hepatoprotective potential of CG extract was examined in experimental model of carbon tetrachloride (CCl( 4))-induced hepatotoxicity. Acute and subchronic toxicity tests revealed that CG extract is non-toxic and its median lethal dose (LD(50)) value is >5000 mg/kg bodyweight. Also, rats pretreated with CG extract followed by administration of CCl(4) recorded significant decrement in plasma marker enzymes of hepatic damage, total bilirubin content and hepatic lipid peroxidation. While, hepatic reduced glutathione, ascorbic acid content, activity levels of superoxide and catalase and plasma total protein content were significantly increased. Microscopic examination of liver showed that pretreatment with CG extract prevented CCl(4)-induced hepatic damage in CG + CCl( 4) group. CG extract has hepatoprotective potential by modulating activity levels of enzymes and metabolites governing liver function and by helping in maintaining cellular integrity of hepatocytes that is comparable with that of standard drug silymarin. CG extract exhibits potent hepatoprotective activity against CCl(4)-induced hepatic damage but does not exhibit any toxic manifestations.

Topics: Animals; Antioxidants; Ascorbic Acid; Biomarkers; Carbon Tetrachloride Poisoning; Catalase; Chemical and Drug Induced Liver Injury; Clerodendrum; Glutathione; Lethal Dose 50; Lipid Peroxidation; Male; Mice; Phytotherapy; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Superoxide Dismutase; Toxicity Tests

The present study aimed to evaluate the protective and curative effects of the 15 KD protein isolated from the seeds of Peganum harmala L. against carbon tetrachloride (CCl4) induced oxidative stress in rats.. In the protective study, animals were pretreated intraperitoneally with 15 KD isolated protein at doses of 4 and 8 mg/kg body weight as well as vitamin C (250 mg/kg body weight p.o) for 7 days and then challenged with CCl4 orally (1 ml/kg body weight) in olive oil (50%) for 2 days. In the curative study, rats were administered CCl4 orally for 2 days, then treated intraperitoneally with 15 KD protein (4 and 8 mg/kg body weight) and orally with vitamin C.. Administration of CCl4 induced induction in malondialdehyde (MDA) and decrease in reduced glutathione (GSH) levels as well as glutathione-S-transferase (GST) activity in brain, testes and erythrocytes. The activity of acetylcholinesterase (AchE) in brain was also inhibited by CCl4 administration.. Treatment of rats either pre or post CCl4 intoxication successfully alleviated the oxidative stress in the brain, testes and erythrocytes of the experimental animals. Data also showed that the isolated protein possessed strong antioxidant activity comparable to that of vitamin C.

Topics: Acetylcholinesterase; Animals; Antioxidants; Ascorbic Acid; Brain; Carbon Tetrachloride Poisoning; Drug Evaluation, Preclinical; Erythrocytes; Glutathione; Glutathione Transferase; Male; Malondialdehyde; Molecular Weight; Oxidative Stress; Peganum; Plant Extracts; Proteins; Rats; Seeds; Testis

Senescence marker protein 30 (SMP30), an important aging marker molecule that is highly expressed in the liver, has been known to protect hepatocytes from apoptosis by the synthesis of vitamin C. To explore the function of SMP30 in liver fibrosis, the effect of SMP30 deficiency on liver fibrosis was investigated in SMP30 knockout (KO) mice. Moreover, the in vivo results were further confirmed by way of hepatic stellate cell (HSC) isolation. We demonstrated that carbon tetrachloride (CCl(4))-induced liver fibrosis and the nuclear translocation of p-Smad2/3, the immediate downstream of transforming growth factor beta (TGF-beta), were significantly inhibited in the liver of SMP30 KO mice compared with wildtype (WT) mice. We also confirmed that both WT and SMP30 KO HSCs did not express SMP30. Finally, we further confirmed that up-regulation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) caused by a lack of vitamin C was the pivotal factor in the mechanisms for attenuated liver fibrosis of SMP30 KO mice, and feeding with vitamin C restored CCl(4)-induced liver fibrosis in SMP30 KO mice.. Vitamin C deficiency by SMP30 depletion attenuated liver fibrosis by way of up-regulated PPAR-gamma expression in SMP30 KO mice. Our results provide, for the first time, the possible mechanisms underlying inhibition of HSC activation associated with vitamin C and PPAR-gamma up-regulation in liver fibrosis of SMP30 KO mice.

Topics: Animals; Ascorbic Acid; Calcium-Binding Proteins; Carbon Tetrachloride Poisoning; Hepatic Stellate Cells; Intracellular Signaling Peptides and Proteins; Liver Cirrhosis; Male; Mice; Mice, Knockout; PPAR gamma; Smad Proteins

CCl(4) (0.5 ml/kg as CCl(4)) was orally administered to rats. Twelve hours after administration of CCl(4), plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, indicators of liver necrosis, were significantly higher than those in the control group showing that active liver necrosis took place. At the same time the level of liver vitamin C was decreased significantly compared to that in the control group. Oral administration of 100 mg/kg each of celecoxib 3 and 8 h after CCl(4) treatment did not change plasma ALT and AST and liver vitamin C levels 12 h after CCl(4) treatment, but 24 h after CCl(4) treatment, significantly decreased plasma ALT and AST levels and elevated liver vitamin C level. These finding suggested that celecoxib effectively ameliorated the necrotic action and the oxidative stress induced by CCl(4) in the second phase. Although the plasma levels of all ceramide species were significantly increased 24 h after CCl(4) intoxication, treatment with celecoxib significantly reduced the total ceramide concentration in plasma. These results indicated that celecoxib significantly ameliorated the toxicity of CCl(4) in the second phase.

Topics: Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Carbon Tetrachloride Poisoning; Celecoxib; Ceramides; Chemical and Drug Induced Liver Injury; Cyclooxygenase 2 Inhibitors; Liver; Male; Necrosis; Oxidative Stress; Pyrazoles; Rats; Rats, Wistar; Sulfonamides

Royal Jelly (RJ) is used in the Turkish folk medicine for the treatment of number of disorders. The present study describes the hepatoprotective and antioxidant activities of the RJ against carbon tetrachloride (CCl(4))-induced acute liver damage. Sprague-Dawley rats were used for the experiment. CCl(4) (0.8 ml/kg; s.c.) and RJ (50, 100, 200mg/kg; orally) were given every other day, for 20 days. Malondialdehyde, reduced glutathione in whole blood and tissues; ceruloplasmin, sialic acid, ascorbic acid, retinol, β-carotene and liver enzymes levels in serum were measured. Additionally, histopathological alterations in the liver were examined. RJ exerted the significant protective effect on liver damage as well as on oxidative stress induced by CCl(4), resulting in reduced lipid peroxidation and improved endogenous antioxidant defence systems. It also reduced the elevated levels of liver enzymes. Histopathological study further confirmed the hepatoprotective effect of RJ, when compared with the CCl(4) treated control groups. In conclusion, present study reveals biological evidence that supports the use of RJ in the treatment of chemical-induced hepatotoxicity.

Topics: Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; beta Carotene; Carbon Tetrachloride Poisoning; Fatty Acids; Glutathione; Liver; Male; Malondialdehyde; N-Acetylneuraminic Acid; Protective Agents; Rats; Rats, Sprague-Dawley; Vitamin A; Vitamins

Carbon tetrachloride (CCl4) is a model for studying free radical-induced liver injury and screening hepato-protective drugs. Numerous studies have reported the involvement of oxidative stress in CCl4-induced liver damage and the hepato-protective effects mediated by different antioxidants. The present study examined the effects of diphenyl diselenide, (PhSe)2, on hepatotoxicity induced by CCl4 in rats. To this end, male Wistar rats received (PhSe)2 by oral route at the dosage of 31.2 mg/kg for one or two days. After the second day of treatment, rats received CCl4 orally in a single dose. The liver and kidney were utilized for determination of histopathology, biochemical [aspartate (ALT) and alanine (AST) aminotransferases, alkaline phosphatase (ALP), total bilirrubin (TB) and gamaglutamyl transferase (GGT)] and toxicological parameters [thiobarbituric reactive species (TBARS) levels, catalase activity, ascorbic acid, nonprotein thiols (NPSH) and aminolevulinate dehydratase (-ALA-D) activity]. Repeated administration of (PhSe)2 caused a marked potentiation of hepatotoxicity induced by CCl4 exposure, as manifested by an increase in biochemical parameters (AST, ALT, ALP, GGT and BT) and severe alteration in histopathology. This study also demonstrated a potentiation of TBARS levels and a consequent depletion of important antioxidant defenses including catalase and ascorbic acid. Pre-treatment with a single dose of (PhSe)2 prevented the effect of strychnine, a substrate for CYPs, abolishing lethality in mice. This result indicates that (PhSe)2 prevented animal death, suggesting an activator action of (PhSe)2 in CYPs. This study clearly indicates that (PhSe)2 potentiated acute hepatic damage induced by CCl4.

Topics: Administration, Oral; Alanine Transaminase; Animals; Ascorbic Acid; Aspartate Aminotransferases; Benzene Derivatives; Bilirubin; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Catalase; Creatinine; Drug Synergism; Drug-Related Side Effects and Adverse Reactions; gamma-Glutamyltransferase; Lipid Peroxidation; Liver; Male; Organoselenium Compounds; Porphobilinogen Synthase; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Urea

Carbon tetrachloride (1 ml/kg body weight as a 1:1 mixture of CCl(4) and mineral oil) was orally administered to rats. After 12 h, the activity of plasma ALT (alanine aminotransferase) was significantly higher than that of the control group, and plasma ALT and AST (aspartate aminotransferase) activities significantly increased 24 h after CCl(4) administration. These results indicated that the necrotic process had initiated at about 12 h and developed thereafter. After 6-24 h of CCl(4) administration, the hepatic level of vitamin C, the most sensitive indicator of oxidative stress, decreased significantly, indicating that oxidative stress was significantly enhanced 6 h after CCl(4) intoxication and thereafter. Oral administration of vitamin E (1 ml/kg body weight as a 1:1 mixture of alpha-tocopherol and mineral oil) 12 h before CCl(4) administration caused a significant elevation of liver vitamin E level and ameliorated liver necrosis 24 h after CCl(4) intoxication based on plasma AST and ALT. Vitamin E also significantly restored the hepatic vitamin C concentration 12 and 24 h after CCl(4) intoxication, demonstrating that vitamin E functioned as an antioxidant. The liver vitamin E concentration was not changed by vitamin E supplementation to rats that did not receive CCl(4). This result indicated that vitamin E accumulated in the damaged liver. The activation of JNK, ERK1/2 and p38 MAPK took place 1.5 h after CCl(4) administration. Co-administration of alpha-tocopherol with CCl(4) did not affect these early changes in MAPKs.

Topics: Alanine Transaminase; alpha-Tocopherol; Animals; Ascorbic Acid; Aspartate Aminotransferases; Carbon Tetrachloride Poisoning; Liver; Male; Necrosis; Rats; Rats, Wistar; Time Factors; Vitamin E

We examined the effect of a nutrient mixture (NM) that contains lysine, proline, ascorbic acid, and green tea extract in mice treated with carbon tetrachloride (CCl4), a model of liver injury in which free radical, oxidative stress, and cytokine production are closely linked. Seven-week-old male Imprinting Control Region (ICR) mice were divided into four groups (A-D) of five animals each. Groups A and C mice were fed a regular diet for 2 weeks, whereas groups B and D mice were supplemented with 0.5% NM (w/w) during that period. Groups A and B received corn oil i.p., whereas groups C and D received CCl4 (25 microL/kg, in corn oil, i.p.). All animals were killed 24 h after CCl4 administration, serum was collected to assess liver and kidney functions, and livers and kidneys were excised for histology. Mean serum aspartate aminotransferase and alanine aminotransferase were comparable in groups A and B, increased markedly in group C, and significantly lowered in group D compared with group C. CCl4 had no significant effect on renal markers (blood urea nitrogen [BUN], creatinine, and BUN/creatinine ratio). CCl4 administration caused an intense degree of liver necrosis that was less severe in the NM fed group D. These results indicate that NM could be a useful supplement in preventing acute chemical-induced liver toxicity.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Ascorbic Acid; Aspartate Aminotransferases; Camellia sinensis; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Drug Combinations; Food; Kidney; Liver; Lysine; Male; Mice; Mice, Inbred ICR; Organ Size; Plant Extracts; Proline

The purpose of this study was to investigate the protective effects of the saponins isolated from the root of Platycodi Radix (Changkil saponins: CKS) on carbon tetrachloride (CCl(4))-induced hepatotoxicities in mice. Pretreatment with CKS prior to the administration of CCl(4) significantly prevented the increase in serum alanine aminotransferase and aspartate aminotransferase activities and hepatic lipid peroxidation formation. In addition, CKS prevented CCl(4)-induced apoptosis and necrosis, as indicated by a liver histopathologic study and DNA laddering. To determine whether Fas/Fas ligand (FasL) pathway involved in CCl(4)-induced acute liver injury, Fas and FasL proteins and caspase-3, -8 activities were tested by western blotting and ELISA. CKS markedly decreased CCl(4)-induced Fas/FasL protein expression levels and in turn attenuated CCl(4)-induced caspase-3, -8 activities in mouse livers. Additionally, CKS protected the CCl(4)-induced depletion of hepatic glutathione levels. The effect of CKS on CYP2E1, the major isozyme involved in CCl(4) bioactivation, was investigated. Treatment with CKS resulted in a significant decrease in the CYP2E1-dependent hydroxylation of aniline. In addition, CKS exhibited antioxidant effects on FeCl(2)-ascorbate induced lipid peroxidation in liver homogenates, and on superoxide radical scavenging activity. These findings suggest that the protective effects of CKS against CCl(4)-induced acute liver injury possibly involve mechanisms related to its ability to block CYP2El-mediated CCl(4) bioactivation and its free radical scavenging effects, and that is also protects against Fas/FasL pathway mediated apoptosis.

Topics: Animals; Ascorbic Acid; Blotting, Western; Campanulaceae; Carbon Tetrachloride Poisoning; Caspase 3; Caspase 8; Chemical and Drug Induced Liver Injury; Chlorides; Cytochrome P-450 CYP2E1; DNA; Dose-Response Relationship, Drug; Fas Ligand Protein; Ferric Compounds; Free Radical Scavengers; Glutathione; Glutathione Transferase; Lipid Peroxidation; Liver; Liver Function Tests; Male; Mice; Mice, Inbred ICR; Saponins

Arazyme is a novel protease produced by the HY-3 strain of Aranicola proteolyticus, which is a Gram-negative aerobic bacterium that has been isolated from the intestine of the spider Nephila clavata. This study focused on the hepatoprotective effect of Arazyme on carbon tetrachloride (CCl4)-induced acute hepatic injury in senescence marker protein 30 (SMP30) knock-out (KO) mice and SMP30 wild-type (WT) mice. WT mice and SMP30 KO mice were divided into eight groups as follows: (i) two negative control groups (G1, G5) which were treated with a single intraperitoneal (i.p.) olive oil injection. (ii) Two positive control groups (G2, G6) which received a single i.p. CCl4 (0.4mL/kg) injection. (iii) Two vitamin C-treated groups (G3, G7) which received a single oral administration of vitamin C (100mg/kg) and were injected with a single i.p. CCl4 (0.4mL/kg). (iv) Two Arazyme-treated groups (G4, G8) which received a single oral administration of Arazyme (500mg/kg) and were injected with a single i.p. CCl4 (0.4mL/kg). Through present study, we could find that Arazyme-treated groups showed decreased degree of liver injury, increased expression of SMP30, decreased expression of phospho-Smad3 (p-Smad3), elevated expression of antioxidant proteins including sorbitol dehydrogenase, dihydropteridine reductase (DHPR), dehydrofolate reductase (DHFR), NADH dehydrogenase, glutathione S-transferase kappa 1 (GSTK1) and phospholipid hydroperoxide glutathione peroxidase (PHGPx) compared with non-Arazyme-treated groups. Therefore, it is concluded that Arazyme plays a significant role in protecting injured hepatocytes by increasing the expression of SMP30, inhibiting the transforming growth factor-beta (TGF-beta)/Smad pathway and elevating the expression of antioxidant proteins.

Topics: Animals; Antioxidants; Ascorbic Acid; Calcium-Binding Proteins; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Chemoprevention; Disease Models, Animal; Female; Fluorescent Antibody Technique, Indirect; Immunoenzyme Techniques; Intracellular Signaling Peptides and Proteins; Liver; Male; Metalloproteases; Mice; Mice, Knockout; Oxidoreductases; Proteomics; Serratia; Smad3 Protein; Specific Pathogen-Free Organisms; Transforming Growth Factor beta; Up-Regulation

Carbon tetrachloride (CCl(4): 4 ml/kg body weight as a 1:1 mixture of CCl(4) and mineral oil) was orally administered to rats. After 12 h the activity of plasma AST (aspartate aminotransferase) and ALT (alanine aminotransferase) was significantly higher than that of the control group and plasma AST and ALT activities increased thereafter. These results indicated that the necrotic process was active at about 12 h and developed thereafter. After 2-24 h of CCl(4) administration, the hepatic level of vitamin C, the most sensitive indicator of oxidative stress, decreased significantly, indicating that oxidative stress was significantly enhanced as early as 2 h after CCl(4) intoxication and thereafter. Phosphorylated JNK (c-Jun NH(2)-terminal kinase) and phospho-ERK1/2 (extracellular signal-regulated kinase1/2) were significantly increased transiently 1-3 h after treatment with CCl(4), while phosphorylated p38 decreased significantly 1-24 h after CCl(4) treatment. These results indicated that the change in MAPKs (mitogen activated protein kinases) slightly preceded that in vitamin C, the most sensitive chemical indicator of oxidative stress.

Topics: Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Disease Models, Animal; Enzyme Activation; JNK Mitogen-Activated Protein Kinases; Liver; Male; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Necrosis; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Rats; Rats, Wistar; Time Factors

This study investigated the protective effects of acteoside, a phenylethanoid glycoside, on the carbon tetrachloride-induced hepatotoxicity as well as the possible mechanisms involved in this protection in mice. Pretreatment with acteoside prior to the administration of carbon tetrachloride significantly prevented the increased serum enzymatic activities of alanine and aspartate aminotransferase in a dose-dependent manner. In addition, pretreatment with acteoside significantly prevented the increase in hepatic malondialdehyde formation and the depletion of the reduced glutathione content in the liver of carbon tetrachloride-intoxicated mice. Carbon tetrachloride-induced hepatotoxicity was also essentially prevented, as indicated by a liver histopathologic study. The effects of acteoside on cytochrome P450 (P450) 2E1, the major isozyme involved in carbon tetrachloride bioactivation were also investigated. Treatment of the mice with acteoside resulted in a significant decrease in the P450 2E1-dependent pnitrophenol and aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the P450 2El protein levels were also lower. Acteoside exhibited anti-oxidant effects on FeCl2-ascorbate induced lipid peroxidation in a mouse liver homogenate, and on superoxide radical scavenging activity. These results suggest that the protective effects of acteoside against the carbon tetrachloride-induced hepatotoxicity possibly involve mechanisms related to its ability to block the P450-mediated carbon tetrachloride bioactivation and free radical scavenging effects.

Topics: Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Chlorides; Cytochrome P-450 CYP2E1; Dose-Response Relationship, Drug; Ferric Compounds; Free Radical Scavengers; Glucosides; Glutathione; Immunoblotting; Lipid Peroxidation; Liver; Liver Function Tests; Male; Mice; Mice, Inbred ICR; Microsomes, Liver; Mixed Function Oxygenases; Phenols; Superoxides

Glutathione S-transferases and glutathione play an important role in the detoxification of most toxic agents. In the present study, the protective effects of some antioxidants (L-ascorbic acid (AA), vitamin E (VE) or garlic) on carbon tetrachloride-induced changes in the activity of alanine amino transferase (ALT), aspartate amino transferase (AST), glutathione S-transferase (GST), and the level of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) were studied. The activities of ALT, and AST were assayed in plasma, whereas the activity of GST and the levels of GSH and TBARS were determined in the livers of rats. The current study included two experiments. In the first experiment, animals received single oral dose of CCl4 (400 mg/kg body weight) after administration of AA (100 mg/kg b.w.), VE (100 mg/kg b.w.) or garlic (800 mg/kg b.w.) as single oral doses. In the second experiment, rats received repeated oral doses of antioxidants for 12 consecutive days followed by a single oral dose of CCl4 on the 13th day and killed after that by 24 h. Treatment of male rats with CCl4 significantly increased the activity of ALT and AST in plasma, and the levels of both GSH and TBARS in the liver. On the other hand, CCl4 inhibited the activity of GST after single dose treatment. Single-dose treatments of rats with AA, VE or garlic prior to the administration of CCl4 could not restore the alterations in the activity of ALT and AST caused by CCl4 to the normal control level. However, repeated dose treatments with these agents restored such alterations to the normal level. We observed that VE is more effective than AA and garlic in restoring the inhibition of GST activity caused by CCl4 to the normal level after single dose treatments. On the other hand, AA and VE are more effective than garlic in restoring the induced TBARS level caused by CCl4 to the normal control level after repeated dose treatments. It has been observed that the tested antioxidants were able to antagonize the toxic effects of CCl4, and such counteracting effects were more pronounced when they were administered as repeated doses prior to administration of CCl4.

Topics: Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Garlic; Glutathione; Glutathione Transferase; Liver; Male; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Thiobarbituric Acid Reactive Substances; Vitamin E

Antioxidants in the blood plasma of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. For this initial study an animal model of CCl(4) poisoning was studied. The time (2, 7, and 16 h) and dose (120 and 1200 mg/kg, intraperitoneally)-dependent effects of CCl(4) on plasma levels of alpha-tocopherol, coenzyme Q (CoQ), ascorbic acid, glutathione (GSH and GSSG), uric acid, and total antioxidant capacity were investigated to determine whether the oxidative effects of CCl(4) would result in losses of antioxidants from plasma. Concentrations of alpha-tocopherol and CoQ were decreased in CCl(4)-treated rats. Because of concomitant decreases in cholesterol and triglycerides, it was impossible to dissociate oxidation of alpha-tocopherol and the loss of CoQ from generalized lipid changes, due to liver damage. Ascorbic acid levels were higher with treatment at the earliest time point; the ratio of GSH to GSSG generally declined, and uric acid remained unchanged. Total antioxidant capacity showed no significant change except for 16 h after the high dose, when it was increased. These results suggest that plasma changes caused by liver malfunction and rupture of liver cells together with a decrease in plasma lipids do not permit an unambiguous interpretation of the results and impede detection of any potential changes in the antioxidant status of the plasma.

Topics: Animals; Antioxidants; Ascorbic Acid; Biomarkers; Carbon Tetrachloride Poisoning; Disease Models, Animal; Electron Spin Resonance Spectroscopy; Free Radicals; Glutathione; Liver; Oxidative Stress; Rats; Rats, Inbred F344; Ubiquinone; Uric Acid; Vitamin E

The hepatoprotective effect of a preparation of human urine (PHU) was assessed against short-term carbon tetrachloride (CCl4) treatment in rats. Significant prevention of liver injury by PHU was found after CCl4 treatment, judging by the changes of serum biochemical parameters, and hepatic protein and triglyceride contents. The increased liver lipid peroxidation, and decreased liver vitamin C concentrations observed after CCl4 treatment were significantly prevented by PHU administration. The increase in liver glutathione (GSH) contents observed after CCl4 treatment was further increased by PHU treatment. Liver catalase activity decreased after CCl4 treatment, while liver superoxide dismutase and GSH-peroxidase activities did not change. PHU administration further inhibited the decrease in liver catalase activity after CCl4 treatment. These results indicate that PHU administration can prevent liver injury induced by CCl4 in rats by inhibiting enhanced lipid peroxidation and by improving disrupted active oxygen metabolism in the injured liver.

Topics: Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Catalase; Glutathione; Glutathione Peroxidase; Humans; Lipid Peroxidation; Liver; Liver Function Tests; Male; Oxygen Consumption; Proteins; Rats; Rats, Wistar; Superoxide Dismutase; Triglycerides; Urine

The yield, composition, and some pharmacological activities (hepatoprotective and antioxidant) of the essential oil of Santolina canescens aerial parts have been investigated. The essential oil qualitative data were determined by gc and gc-ms. The main component, santolindiacetylene [1], was isolated and characterized by spectral methods, and the structure assigned as 1-(2'-naphthyl)hexa-2,4-diyne. The protective activities of the essential oil and its main component [1] were evaluated against carbon tetrachloride-induced hepatotoxicity in a rat model. In both cases a significant hepatoprotective effect was observed, as evident from the strong decrease of elevated GPT serum levels caused by carbon tetrachloride-induced hepatic damage.

Topics: Alkynes; Animals; Antioxidants; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Diynes; Female; Free Radical Scavengers; Naphthalenes; Oils, Volatile; Plant Oils; Plants, Medicinal; Rats; Rats, Wistar; Spain

Selected serum parameters (enzyme activities and triglycerides) and liver glutathione and vitamin C concentrations were measured in English sole (Parophrys vetulus) after i.p. injection of carbon tetrachloride (CCl4), a hepatotoxin in fish. Serum lactate dehydrogenase (LDH), alkaline phosphatase (AP) and glutamate dehydrogenase (GDH) activities and the concentration of triglycerides increased in a dose-dependent manner 24 hr post injection. Concentrations of glutathione (reduced and oxidized) and ascorbic acid (vitamin C) in liver did not change in response to CCl4 toxicity 24 hr post injection. These studies indicate that serum AP activity and triglyceride concentrations can be useful in assessing the effects of CCl4-induced liver toxicity in this species of marine fish. Serum LDH and GDH activity should be used with some caution in assessing liver damage in English sole, as other tissues represent more likely sources for serum activity. The levels of liver antioxidants do not appear to be significantly affected, 24 hr post injection, by this particular hepatotoxin.

Topics: Alkaline Phosphatase; Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Fishes; Glutamate Dehydrogenase; Glutathione; L-Lactate Dehydrogenase; Liver; Triglycerides

Measurements of pentane and ethane as indices of in vivo lipid peroxidation were made on samples of breath from vitamin C-sufficient and vitamin C-deficient guinea pigs injected with 23 microliters carbon tetrachloride (CCl4)/100 g body wt. Vitamin C-deficient animals produced significantly more pentane and ethane after CCl4 treatment than did vitamin C-sufficient guinea pigs. Pretreatment of vitamin C-deficient animals with 75 mg ascorbic acid/100 g body wt significantly lowered both pentane and ethane evolution. Protection against in vivo lipid peroxidation similar to that provided by ascorbic acid was also found when vitamin C-deficient guinea pigs were pretreated with isoascorbic acid, reduced glutathione, alpha-tocopherol or beta-carotene. When animals were pretreated with the radical scavenger mannitol, a protective effect was also observed as measured by pentane evolution.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carbon Tetrachloride Poisoning; Ethane; Guinea Pigs; Lipid Peroxides; Male; Pentanes; Time Factors

Glutathione (GSH) protects rat liver microsomes against ascorbic acid (0.2 mM)/ferrous iron (10 microM)-induced lipid peroxidation for some time. The inhibitory effect of GSH is concentration-dependent (0.1-1.0 mM). Our data suggest that GSH acts by preventing initial radical formation rather than via radical scavenging or GSH--peroxidase activity. A labile GSH-dependent factor is involved in the inhibition of microsomal lipid peroxidation by GSH, inasmuch as heating the microsomes abolishes the GSH effect. We found that besides heating, lipid peroxidation also destroys the GSH-dependent factor. Consequently, continuous radical stress will produce lipid peroxidation, despite the presence of GSH. Moreover, a detrimental effect of in vivo-induced lipid peroxidation (CCl4-treatment) on the GSH-dependent factor was observed. The implications of the present data for the genesis of and the protection against peroxidative damage are discussed.

Topics: Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Ferrous Compounds; Glutathione; Hot Temperature; Lipid Peroxides; Male; Microsomes, Liver; Rats; Rats, Inbred Strains; Time Factors; Tissue Extracts

The excretion of ascorbic acid and hippuric acid in the urine as liver function tests has no marked advantages when compared with other tests (activities of serum enzymes glutamate dehydrogenase and L-alanine: 2-oxoglutarate aminotransferase, hexobarbital sleeping time).

Topics: Aminopyrine; Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Female; Hexobarbital; Hippurates; Male; Rats; Sleep; Thioacetamide; Time Factors

The authors investigated the effects of the administration of thioacetamide, carbon tetrachloride and aminophenazone on the excretion of ascorbic acid and hippuric acid in adult male and female Wistar rats. After a single application of thioacetamide and aminophenazone, the ascorbic acid content in the urine showed a dose-dependent increase, whereas that in the liver had decreased. This increase in the urinary ascorbic acid might be due to a release of stored ascorbic acid from the liver cells. When thioacetamide was given for a prolonged period, the ascorbic acid content in the urine increased at the beginning; later one, at the end of three weeks, it was slightly inferior to the control value. Both single and repeated applications of thioacetamide led to a decrease in the excretion of hippuric acid in the urine, which is attributed to an impairment of the mitochondrial hippuric acid synthesis. Long-term treatment with aminophenazone resulted in an increase of ascorbic acid in the urine, which is indicative of an induction effect, whereas the ascorbic acid content in the liver remained unchanged. There was no effect on the excretion of hippuric acid. In regard to their use in the toxicological evaluation of drugs, these two metabolic effects offer no decisive advantage over current liver function tests.

Topics: Aminopyrine; Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Enzymes; Female; Hexobarbital; Hippurates; Liver; Liver Function Tests; Male; Rats; Sleep; Thioacetamide; Time Factors

Topics: Alcoholic Intoxication; Alkenes; Animals; Antioxidants; Ascorbic Acid; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Diet; Ethanol; Fatty Liver; Humans; Lipid Metabolism; Lipids; Liver; Neurologic Manifestations; Pyrazoles; Rats; Triglycerides; Vitamin E; Vitamin E Deficiency

Topics: Aminopyrine N-Demethylase; Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Cytochrome Reductases; In Vitro Techniques; Lipid Metabolism; Male; Malonates; Microsomes, Liver; NADP; Oxidation-Reduction; Peroxides; Pharmaceutical Preparations; Proteins; Rats

Topics: Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Chronic Disease; Glucose; Liver; Liver Regeneration; Male; Methods; Rats

Topics: Adenosine Diphosphate; Aniline Compounds; Animals; Ascorbic Acid; Calcium; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Cytochromes; Dinitrophenols; Electron Transport; Ketoglutaric Acids; Kinetics; Male; Mitochondria, Liver; Mitochondrial Swelling; NAD; Oxidative Phosphorylation; Oxygen Consumption; Polarography; Rats; Succinates; Time Factors

Topics: Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Cytochrome c Group; Electron Transport; Glutamates; In Vitro Techniques; Ketoglutarate Dehydrogenase Complex; Kinetics; Male; Mitochondria, Liver; NAD; Oxidation-Reduction; Oxygen Consumption; Phenylenediamines; Pyruvates; Rats; Succinates

Topics: Animals; Anura; Ascorbic Acid; Carbon Tetrachloride Poisoning; Histocytochemistry; Hydroxysteroid Dehydrogenases; Leydig Cells; Male; Sertoli Cells; Testis

Topics: Anabolic Agents; Animals; Ascorbic Acid; Body Weight; Carbon Tetrachloride Poisoning; Drug Synergism; Female; Guinea Pigs; Injections, Subcutaneous; Liver Cirrhosis; Male; Nicotinic Acids; Organ Size; Prednisone; Sex Factors; Vitamin B 12

Topics: Animals; Antidotes; Ascorbic Acid; Carbon Tetrachloride Poisoning; Chloroform; Male; Mice

Topics: Animals; Ascorbic Acid; Biotin; Carbon Tetrachloride Poisoning; Centrifugation; Chemical and Drug Induced Liver Injury; Folic Acid; Liver; Necrosis; Nicotinic Acids; Pantothenic Acid; Proteins; Pyridoxine; Rats; Riboflavin; Specimen Handling; Thiamine; Vitamin A; Vitamin B 12; Vitamin E; Vitamins

Topics: Animals; Ascorbic Acid; Atropa belladonna; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Drug Synergism; Liver; Liver Diseases; Liver Regeneration; Mice; Nicotinic Acids; Phytotherapy; Plants, Medicinal; Plants, Toxic; Vitamin E

Topics: Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Dermatologic Agents; Drug Synergism; Mitochondria, Liver; Oxidative Phosphorylation; Oxygen Consumption; Phosphorus; Rats; Stimulation, Chemical; Tannins; Vitamin B Complex

Topics: Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Catechols; Ceruloplasmin; Dermatologic Agents; Drug Synergism; Flavonoids; Liver; Liver Glycogen; Phenols; Plant Extracts; Rats; Rutin; Stimulation, Chemical; Tannins

Topics: Animals; Ascorbic Acid; Barbiturates; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Dogs; Enzyme Induction; Hexobarbital; Sleep

Topics: Adrenal Glands; Adrenocortical Hyperfunction; Animals; Ascorbic Acid; Body Weight; Carbon Tetrachloride Poisoning; Female; Hypertrophy; Organ Size; Rats

Topics: Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Dermatologic Agents; Mitochondria, Liver; Oxidative Phosphorylation; Oxygen Consumption; Rats; Succinates; Tannins

Topics: Aging; Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Chlorobutanol; Gossypium; Granulation Tissue; Liver Diseases; Metabolism; Necrosis; Rats; Starvation

Topics: Acetylcholine; Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Electron Transport; Epinephrine; Histocytochemistry; In Vitro Techniques; Liver; Liver Cirrhosis, Experimental; Norepinephrine; Rabbits; Sympathetic Nervous System; Transaminases; Vitamin A; Vitamin E

Topics: Animals; Ascorbic Acid; Carbohydrate Metabolism; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Liver Glycogen; Phosphorus; Rabbits; Thiamine

Topics: Alanine Transaminase; Ascorbic Acid; Aspartate Aminotransferases; Blood; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Clinical Enzyme Tests; D-Alanine Transaminase; Hepatitis; Liver Diseases; Rats; Research; Toxicology; Transaminases

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Guinea Pigs; Lipoproteins; Vitamins

Topics: Ascorbic Acid; Carbon Tetrachloride; Carbon Tetrachloride Poisoning