allopurinol and Carbon-Tetrachloride-Poisoning

In the course of searching hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine brown alga Spatoglossum variabile Figaro et DE Notar (Dictyoaceae) against CCl₄-induced liver damage in Wistar rats was investigated. The compounds were first investigated for in vitro radical scavenging potential and were also tested for β-glucuronidase inhibition to further explore the relationship between hepatoprotection and antiradical potential.. The compounds cinnamic acid esters 1 and 2 and aurone derivatives 3 and 4 were first investigated for in vitro radical scavenging potential against 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH), and superoxide anion radicals. In vivo hepatoprotective studies were performed in seven groups (n = 6) of Wistar rats. The test groups were pretreated with compounds (10 mg/kg body weight, po) orally for 30 min before the intraperitoneal administration of a dose of 20% CCl₄ diluted with dietary cooking oil. Moreover, compounds were also tested for β-glucuronidase inhibition to explore the relationship between hepatoprotection and radical scavenging potential.. The test compounds 1-4 were found to exhibit antiradical activity against 1,1-diphenyl-2-picrylhydrazyl radicals with IC₅₀ values ranging between 54 and 138 µM, whereas aurone derivatives 3 and 4 additionally exhibited superoxide anion scavenging effects with IC₅₀ values of 95 and 87 µM, respectively. In addition, these compounds were found to be weak inhibitors of xanthine oxidase (IC₅₀ ≥1000 µM). In animal model, pretreatment with compounds 2-4 significantly blocked the CCl₄-induced increase in the levels of the serum biochemical markers.. It appears that the hepatoprotection afforded by these compounds was mainly due to their radical scavenging activity that protected the cells from the free radicals generated by CCl₄-induced hepatotoxicity.

Topics: Animals; Benzofurans; Biomarkers; Carbon Tetrachloride Poisoning; Cell Survival; Cinnamates; Drug Discovery; Enzyme Inhibitors; Escherichia coli Proteins; Free Radical Scavengers; Glucuronidase; Humans; Liver; Male; Milk Proteins; Neutrophils; Phaeophyceae; Rats; Rats, Wistar; Xanthine Oxidase

Carbon tetrachloride exerts its toxicity in rat kidneys through oxidative stress. Launaea procumbens is used ethnopharmacologically in renal disorders. Its methanolic, chloroform, ethyl acetate, and n-hexane fractions were evaluated against CCl(4)-induced nephrotoxicity in rat.. Among 16 groups, one was given CCl(4) of 3ml/kg body weight (30% in olive oil i.p.) twice a week for 4 weeks. Others were orally fed with extracts (100, 200mg/kg b.w.) or rutin (50mg/kg b.w.) after 48h of CCl(4) or 200mg/kg b.w. of extracts without CCl(4)-treatment twice a week for 4 weeks.. CCl(4) exposure led to a significant oxidative stress in kidneys which was remarkably attenuated with co-administration of various fractions and rutin thereby increased the level of CAT, POD, SOD, GSH, GSR, GST, GSH-Px, quinone reductase, while reduced the xanthine oxidase, gamma-GT, TBARS, H(2)O(2), nitrite, tissue proteins and DNA fragmentation%. Ameliorated effects of fractions and rutin were also recorded for the function of kidneys and the level of urobilinogen, urea, albumin, creatinine, RBC and WBC in urine were decreased. Serum level of creatinine, urobilinogen, BUN, direct bilirubin, total bilirubin and globulin were decreased while total proteins, albumin and creatinine clearance were increased with fractions and rutin. Protective effects of rutin and fractions were also evident on histopathology by reducing glomerular atrophy, tubular degeneration, congestion of blood capillaries, necrosis of epithelium and edema. Similarly body weight was increased while kidney and relative kidney weight was decreased with co-administration of fractions and rutin.. It is suggested that Launaea procumbens effectively protect kidneys against the CCl(4)-induced oxidative damage in rats, through antioxidant and free radical scavenging effects of flavonoids and saponins present in the fractions.

Topics: Animals; Antioxidants; Asteraceae; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Creatinine; Glutathione; Hexanes; Hydrogen Peroxide; Kidney; Kidney Diseases; Male; Nitrites; Oxidative Stress; Rats; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Xanthine Oxidase

This study was carried out to investigate the anti-oxidative and hepatoprotective effects of glycoprotein isolated from Zanthoxylum piperitum DC fruit (ZPDC glycoprotein). ZPDC glycoprotein showed a single band with molecular weight of 24kDa on the 18% sodium dodecyl sulfate-polyacrylamide gel and consists of a carbohydrate component (18%) and a protein component (82%). We found that ZPDC glycoprotein has a strong scavenging activity against DPPH, superoxide anion, and hydroxyl radicals without any pro-oxidant activity in the cell-free system. In hepatocyte cell lines (Chang liver and BNL CL.2 cells), the results showed that ZPDC glycoprotein has an inhibitory effect on hypoxanthine/xanthine oxidase- or glucose/glucose oxidase-induced cytotoxicity in a dose-dependent manner. In addition, administration of ZPDC glycoprotein (20mg/kg) lowers the levels of lactate dehydrogenase, alanine transaminase, and thiobarbituric acid reactive substances, whereas increases that of nitric oxide, accompanying the normalizing effects on the activity of hepatic anti-oxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in mouse model of carbon tetrachloride-stimulated acute liver injury. On the whole the results suggest that ZPDC glycoprotein can be a potent hepatoprotective agent as a natural anti-oxidant.

Topics: Alanine Transaminase; Animals; Antioxidants; Biphenyl Compounds; Carbon Tetrachloride Poisoning; Cell Line; Cell-Free System; Chemical and Drug Induced Liver Injury; Free Radical Scavengers; Fruit; Glucose Oxidase; Glycoproteins; Hepatocytes; Humans; L-Lactate Dehydrogenase; Male; Mice; Mice, Inbred ICR; Nitric Oxide; Picrates; Pronase; Protective Agents; Superoxides; Thiobarbituric Acid Reactive Substances; Xanthine Oxidase; Zanthoxylum

The hepatic lesion produced as a result of oxidative stress is of wide occurrence. In the present study, the effect of tungsten on liver necrosis and fulminant hepatic failure (FHF) has been studied in rats treated with various compounds known to produce oxidative stress. Supplementation of animals with sodium tungstate for 7 weeks before the induction of liver injury by chemicals including thioacetamide (TAA), carbon tetrachloride (CCl(4)), or chloroform (CHCl(3)) could protect progression of hepatic injury. Various biochemical changes associated with liver damage and oxidative stress were measured. Hepatic malondialdehyde content, endogenous tripeptide, and reduced glutathione were measured as oxidative stress markers. The activity of xanthine oxidase, which generates reactive oxygen species (ROS) as a by-product, was also determined and found to be perturbed. Tungsten supplementation to rats caused a significant decrease in lipid peroxidation and lowered the levels of the biochemical markers of hepatic lesions produced by TAA, CCl(4) (CCl(4)), or CHCl(3). Tungsten could also cause an increase in the survival rate in rats receiving lethal doses of TAA, CCl(4), or CHCl(3). The protective effect of tungsten, however, is suggested to be limited to the conditions where the hepatic lesion is reported to be due to the generation of ROS. The progression of liver injury produced by the compounds causing oxidative stress without initiating the generation of free radicals such as bromobenzene (BB), or acetaminophen (AAP), could not be inhibited by tungsten. The possible mechanism explaining the role of oxyanionic form of tungsten in free radical-induced hepatic lesions is discussed.

Topics: Acetaminophen; Alkaline Phosphatase; Allopurinol; Animals; Bromobenzenes; Carbon Tetrachloride Poisoning; Chloroform; Dimethyl Sulfoxide; Female; Lethal Dose 50; Liver; Liver Failure; Necrosis; Oxidative Stress; Rats; Rats, Wistar; Thioacetamide; Transaminases; Tungsten Compounds

The cytochrome P-450 system is a sensitive indicator in different forms of experimental liver diseases in the rat. Both CCl4 and ethanol produce a liver damage by free radical mechanisms causing a lesion of liver cell endoplasmic reticulum. Protective effects of antioxidants on CCl4 or ethanol induced liver damage were investigated on this basis in adult Wistar rats. The strongest protective effect in CCl4 treated animals was shown to be exerted by allopurinol. The other three antioxidants (cyanidanol, MTDQ monomer and MTDQ dimer) could not prevent the CCl4 induced changes, measured by liver/body mass quotient, P-450 concentration, ethylmorphine N-demethylation and ethoxycoumarin O-deethylation. Ethanol in the given doses did not produce any distinct effect on the test parameters. The most sensitive parameter was the ethylmorphine N-demethylation. In conclusion CCl4 intoxication is a suitable model for studying radical initiated liver injuries. The mechanisms of the hepatoprotective effects of the four substances are different.

Topics: Allopurinol; Animals; Antioxidants; Carbon Tetrachloride Poisoning; Catechin; Cytochrome P-450 Enzyme System; Male; Microsomes, Liver; Mixed Function Oxygenases; Quinolines; Rats; Rats, Inbred Strains

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cholestasis; Chromatography, Gel; Female; Hemochromatosis; Hepatic Encephalopathy; Hepatitis; Hepatitis A; Humans; Intestinal Diseases; Liver Cirrhosis; Liver Diseases; Male; Myocardial Infarction; Rats; Spectrophotometry; Xanthine Oxidase

Topics: Animals; Carbon Tetrachloride Poisoning; Chromatography; Cytochromes; Female; Liver Diseases; Male; Microsomes; NAD; Oxidoreductases; Rats; Starvation; Transaminases; Xanthine Oxidase

Topics: Aminohydrolases; Blood Chemical Analysis; Borates; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Dogs; Guanine; Guanine Deaminase; Hepatitis; Research; Spectrophotometry; Toxicology; Xanthine Oxidase; Xanthines

Topics: Animals; Blood; Carbon Tetrachloride Poisoning; Colorimetry; Fatty Acids; In Vitro Techniques; Iodine; Rats; Xanthine Oxidase

Topics: Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cholestasis; Hepatitis A; Hepatitis, Animal; Humans; Liver Cirrhosis; Liver Diseases; Mice; Rats; Urate Oxidase; Xanthine Oxidase

Topics: Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Liver; Oxidoreductases; Xanthine Oxidase

Topics: Animals; Blood; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Oxidoreductases; Rats; Serum; Xanthine Oxidase