Hepatotoxicity was induced in vivo by administering ccl 4 to rats that had undergone a 68% partial hepatectomy ph. Carbon tetrachloride ccl 4, a volatile inorganic compound, is a very welldescribed hepatotoxicant. Carbon tetrachloride toxicological overview key points kinetics and metabolism carbon tetrachloride is readily absorbed after ingestion and inhalation, but more slowly through the skin carbon tetrachloride is metabolised by cytochrome p450 enzymes which results in the formation of reactive potentially toxic metabolites. Protective effect of secoisolariciresinol diglycoside in. Protective effect of secoisolariciresinol diglycoside in carbon tetrachloride induced hepatotoxicity in rats sadiq s mareai 1, khalid m naji2, kavishankar gawli 3 and j rajesha 3 1department of chemistry, biochemistry division, university of thamar, thamar, yemen 2department of chemistry, university of sanaa, sanaa, yemen 3department of biochemistry, yuvarajas college, university of. Riboflavin reduces carbon tetrachloride induced increase in tnf riboflavin, a component of flavoproteins plays an important role in hepatoprotection.
Nigella sativa seeds protect against hepatotoxicity and. Carbon tetrachloride 56235 hazard summary carbon tetrachloride may be found in both ambient outdoor and indoor air. Carbon tetrachloride ccl4 creates necrosis in hepatocytes. The most recent work in this field has inaugurated a third revolution in the study of. Mechanism of carbon tetrachlorideinduced hepatotoxicity. Hederin on carbon tetrachlorideinduced hepatotoxicities were investigated in mice. Here, 2weekold weaning and 8weekold adult male icr mice were intraperitoneally injected with ccl4 0. Animals were sacrificed at various times after the administration of 2butanol 2.
Pdf carbon tetrachloride ccl4 induced hepatotoxicity. Carbon tetrachloride ccl 4 is the most perceived chemical substance utilized in developing models of hepatic damage. Carbon tetrachloride ccl 4 is well known to induce hepatotoxicity after being metabolized to trichloromethyl free radical ccl 3 by cyp2e1. Introduction carbon tetrachloride ccl 4 is an important model agent to study the pathogenesis of liver injury boll et al. Research article asian journal of biomedical and pharmaceutical sciences 1 3 2011, 2631 corresponding author. Carbon tetrachloride is most often found in the air as a colorless gas. Formation of novel noncyclooxygenasederived prostanoids f2isoprostanes in carbon tetrachloride hepatotoxicity. Department of health and human services, public health service. Hepatoprotective efffect of a wild edible mushroom on carbon tetrachloride induced hepatotoxicity in mice. Treatment of carbon tetrachloride poisoning with hyperbaric. The hypothesis that ccl4 poisoning exerts its hepatotoxic action via adrenalmedullary discharge of catecholamines and stimulation of sympathetic autonomic.
In the present study the hepatoprotective effect of methonolic extract of c. Metformin met is a potent antidiabetic and redox modulatory agent that has shown anticancer and protective effects on various organs. R i dm c k 516 03 andhra pradesh, india 2d ep art m nof p hc u is,ces lg y k 5 182 a di. The purpose of this study was to investigate the protective effects of puerarin against hepatotoxicity induced by carbon tetrachloride cci 4 and the mechanism of its hepatoprotective effect. Pdf influence of liv52 on carbon tetrachloride induced. Three groups of 10 rats each were subjected to experimental study. You may need a pdf reader to view some of the files on this page. Susceptibility to chlordeconecarbon tetrachloride induced. Various medicinal plants have been used to treat for. The role of alcohol metabolism in 2butanolinduced potentiation of carbon tetrachloride ccl4 hepatotoxicity was studied in rats. Protection against carbon tetrachloride induced hepatotoxicity by protein a. Coadministration of thyme tincture resulted in unexpected exacerbation of ast and alt values in serum, while thyme syrup managed to reduce activites of aminotransferases, in. Sep 26, 2019 toxicological profile for carbon tetrachloride.
Carbon tetrachloride an overview sciencedirect topics. Get a printable copy pdf file of the complete article 1. Acute carbon tetrachloride poisoning in 19 patients. Hepatoprotective mechanisms of taxifolin on carbon tetrachloride. Carbon tetrachlorideinduced hepatotoxicity in rat is. Species differences in carbon tetrachlorideinduced hepatotoxicity. It has also been used as a cleaning fluid in the dry cleaning industry, as. Hepatoprotective effect of cleome gynandra on carbon. Pdf protection against carbon tetrachlorideinduced. Integrated risk information system iris march 2010. The carbon tetrachloride model in mice the authors 2015. Ccl 4induced liver damage was modeled in monolayer cultures of rat primary hepatocytes with a focus on involvement of covalent binding of ccl 4 metabolites to cell components andor peroxidative damage as the cause of injury. Mechanism of carbon tetrachloride induced hepatotoxicity. Hepatotoxicity and mechanism of action of haloalkanes.
Carbon tetrachloride, also known by many other names the most notable being tetrachloromethane, also recognised by the iupac, carbon tet in the cleaning industry, halon104 in firefighting, and refrigerant10 in hvacr is an organic compound with the chemical formula ccl 4. Elzergy1 1 department of zoology, faculty of science, alexandria university, alexandria, egypt. Hepatic injury can be induced by the administration of carbon tetrachloride ccl4 via the production of free radicals. However, there is a limited understanding of pediatric dili. Pdf hepatoprotective efffect of a wild edible mushroom on. Female swiss albino mice were supplied with larginine for 6 days orally, 200 mgkg body weight prior or post to hepatic injury induction. The most recent work in this field has inaugurated a third revolution in the study of carbon tetrachloride hepatotoxicity. Ccl 4 is a biologically inactive and stable substance that is chemically.
The problem formulation document will be available for comment until august 16, 2018 in the docket epahqoppt20160733. In vitro studies were also performed in hepatocytes isolated from ph rats. The principle causes of carbon tetrachloride ccl 4 is induced hepatic damage in lipid peroxidation and decreased activities of antioxidant enzymes and generation of free radicals6,7. If the inline pdf is not rendering correctly, you can download the pdf. Carbon tetrachloride is a clear, nonflammable liquid which is almost insoluble in water. It is also called carbon chloride, methane tetrachloride, perchloromethane, tetrachloroethane, or benziform. Carbon tetrachlorideinduced hepatotoxicity in pregnant and. This article is an attempt to summarize the current understanding of hepatotoxicity of antidiabetic drugs. Hepatoprotective and antioxidant activity of bombax ceiba.
Pdf hepatoprotective effect of cleome gynandra on carbon. R b blain, r reeves, k a ewald, d leonard, e j calabrese, susceptibility to chlordeconecarbon tetrachloride induced hepatotoxicity and lethality is both age and sex dependent. Hepatotoxicity induced by carbon tetrachloride was reflected by a marked elevation of ast and alt activities, and histopathologic alterations. Hepatotoxicity did not receive as much attention as other prevalent complications i.
Liver diseases are one of the fatal disorders due to the vital role of the liver. Gst as an early index of carbon tetrachloride ccl4 toxicity in the rat was investigated and compared with a standard enzyme marker, aspartate aminotransferase ast. Carbon tetrachloride is known to be metabolized by mouse and rat liver and kidney microsomes, by cyp2e1, to yield a trichloromethyl radical, which may be oxygenated to yield phosgene figure 2. This monograph is one in a series of selfinstructional. In particular, for carbon tetrachloride poisoning, at a time when liver triglycerides are increasing rapidly, there is no increase in flux of fatty acids through the plasma compartment. Hepatic toxicity in rats exposed to carbon tetrachloride by inhalation or by. Carbon tetrachlorideinduced liver injury in the rabbit. It is a known animal carcinogen and a potential human carcinogen. Riboflavin attenuates carbon tetrachloride induced oxidative stress. Protective effects of propolis and probiotic lactobacillus acidophilus against carbon tetrachlorideinduced hepatotoxicity in rats. Effect of curcumin and its analogue on lipids in carbon. Abstract background hepatotoxicity induced by carbon tetrachloride ccl4 is used as an experimental model to screen phytochemicals with liver protecting activity. Ccl 4 has become a model for the study of agents that cause localized cellular injury via a freeradical mechanism. The hepatotoxic effects of ccl 4 in the rat were determined in a time and doseresponse study.
Return to the risk evaluation page for carbon tetrachloride. A reassessment of carbon tetrachloride, a model hepatotoxicant and carcinogen, provides an opportunity to incorporate into the assessment biologically relevant mode of action data on its carcinogenesis. It is a colourless liquid with a sweet smell that can be detected at low levels. This effect of ccl4 appears to be reversible and dosedependent. Abdelkader oumeddour 1,2, djahida zaroure 2, raziqua haroune 2, rima zaimeche 2, karima riane 3. Carbon tetrachloride is used to make refrigeration fluid and propellants for aerosol cans. Weaning mice and adult mice exhibit differential carbon. Carbon tetrachloride ccl 4 is regarded as highly toxic. Amelioration of ccl4 induced liver injury in swiss albino. Cleome gynandra has been used widely in indian indigenous system. Carbon tetrachloride ccl4 metabolism via cytochrome p450 leads to. Protective effects of propolis and probiotic lactobacillus. It is a clear liquid with a sweet smell that can be detected at low levels.
Studies on the mechanism of glutathione prevention of. Hydrolysis of phosgene would then result in the formation of co 2, a major in vivo and in vitro metabolite of carbon tetrachloride. Puerarin, the main isoflavone glycoside found in the root ofpueraria lobata, has been used for various medicinal purposes in traditional chinese medicine for thousands of years. Carbon tetrachloride hepatotoxicity pharmacological. Sitosterol protects against carbon tetrachloride hepatotoxicity but not gentamicin nephrotoxicity in rats via the induction of mitochondrial glutathione redox cycling. Formerly used as a drycleaning solvent, carbon tetrachloride has been almost entirely displaced from this application by tetrachloroethylene, which is. Potentiation of carbon tetrachloride hepatotoxicity and lethality in type 2 diabetic rats. Carbon tetrachloride toxicological overview key points kinetics and metabolism carbon tetrachloride is readily absorbed after ingestion and inhalation, but more slowly through the skin carbon tetrachloride is metabolised by cytochrome p450 enzymes which results in. The present work was initiated to investigate the kidney response to hepatic injury induced by ccl4 and its treatment by larginine. The effect of skf 525a on the distribution of carbon tetrachloride in rats. This free radical then initiates lipid peroxidation with subsequent destruc.
Ethanol, and some other alcohols, have been shown to potentiate the hepatotoxicity of carbon tetrachloride, possibly by increasing carbon tetra chlorideinduced lipid peroxidation 16,17. In the present study, the hepatotoxicity induced by a single oral dose 2,000 mgkg of ccl 4 was compared between pregnant gestation days gd and 19 or postpartum postpartum days ppd 1, and 27 and nonpregnant rats. Toxicity was determined by increases in serum sorbitol dehydrogenase and alanine aminotransferase activities measured 24 hr following the treatments. Introduction carbon tetrachloride ccl 4 has been used as a dry cleaning agent, fabric spotting fluid, solvent, reagent in chemical. Carbon tetrachloride ccl4induced hepatic damage in. It is known to cause damage to the liver, lungs, adrenals, and central nervous system in humans and.
Carbon tetrachloride was purchased from sigma, aldrich. Carbon tetrachloride ccl 4induced hepatic damage in experimental sprague dawley rats. Carbon tetrachloride cc l4induced liver damage was achieved by injecting 3 mlkg of ccl 4 intraperitoneally on the twenty first day of feeding the animals in groups 2 to 4 with aqueous extract of x. Effects of pharmaceutical formulations containing thyme on. Hepatotoxicity of trichloroethylene carbon tetrachloride. Protective effect of ricinus communis leaves extract on. All atsdr toxicological profile pdf files are electronic conversions from paper copy or other electronic ascii text files. The present study was aimed to evaluate the efficacy of s. Protection of regenerating liver after partial hepatectomy. In the present study, we examined the effect of hepatic stimulator substance hss on modulating hepatotoxicity induced by carbon tetrachloride ccl 4 in the regenerating rat liver methods. Combination of metformin and luteolin synergistically.
Carbon tetrachloride, when injected directly into the portal venous cannula of an isolated perfused rat liver, inhibited the net outward transport of hepatic triglycerides. Hederin prior to the administration of carbon tetrachloride significantly prevented the increase in serum alanine aminotransferase alt and lactate dehydrogenase ldh activity and lipid peroxidation in a dose dependent manner. Pdf carbon tetrachloride ccl4 induced hepatotoxicity in rats. Role of nigella sativa in carbon tetrachloride induced. In the present study, we examined the effect of hepatic stimulator substance hss on modulating hepatotoxicity induced by carbon tetrachloride ccl 4 in the regenerating rat liver. If the inline pdf is not rendering correctly, you can download the pdf file here. Carbon tetrachloride is a manufactured chemical that does not occur naturally. The primary effects of carbon tetrachloride in humans are on the liver, kidneys, and central nervous system cns. Additionally, carbon tetrachloride was found to enhance haf and liver tumor development in hamsters when given after dimethylnitrosamine as an initiating agent tanaka et al. Potentiation of carbon tetrachloride hepatotoxicity by. Pdf solanum nigrum is used in hepatic disorders in folk medicines. Carbon tetrachloride ccl4 the journal of phytopharmacology. Carbon tetrachloride induces hepatotoxicity via oxidative stress and inflammation.
Carbon tetrachloride ccl 4 is widely used for experimental induction of liver damage5. Carbon tetrachloride iarc 1999a and chloroform iarc 1999b are hepatotoxic chemicals that increase liver neoplasms in mice. Carbon tetrachloride, hepatoprotective, hepatotoxicity, nigella sativa. Human symptoms of acute shortterm inhalation and oral exposures to carbon tetrachloride include headache. Dichloromethane potentiation of carbon tetrachloride. The methanol extracts of plant materials of some plants like casuarina equisetifolia, cajanus cajan, glycosmis pentaphylla, bixa orellana, argemone mexicana, physalis minima, caesalpinia bonduc, belonging to the different family were studied for. Carbon tetrachlorideinduced hepatotoxicity request pdf. The carbon tetrachloride model in mice d scholten1, j trebicka2, c liedtke1, and r weiskirchen3, abstract recently, the need for more standardized operation procedures in experimental liver fibrosis research was suggested due to dramatic changes in european animal welfare rules. The present study was designed to evaluate the role of liv52 in carbon tetrachloride induced liver toxicity.
Hepatotoxicity was induced in rats by carbon tetrachloride ccl 4 treatment. Carbon tetrachloride is a liquid carbon tetrachloride is a manufactured clear liquid with a sweet odor that evaporates easily. Carbon tetrachloride ccl 4 is a wellknown and widely used model for induced liver injury studies mir et al. While the mechanism of carbon tetrachloride hepatotoxicity remains a matter for discussion, the most widely held thesis is that the parent compound undergoes lethal cleavage with the resulting for mation of a free radical. Experimental liver fibrosis in mice can be induced by surgical intervention e. Antioxidant potential of xylopia aethiopica adewale o. Hepatotoxicity was assessed by estimating the activities of marker enzymes and by histological studies. Hepatoprotective effect of cleome gynandra on carbon tetrachloride induced hepatotoxicity in wistar rats sadhu nelson kumar1, kandula ravindra reddy2, kothapalli bonnth chandra sekhar3 and rakhal chandra das4 1d e part mn of ph cl g y. The carbon tetrachloride model in mice d scholten, j. Pdf hepatoprotective activity of methanol extract of. Cbl was evaluated on ccl4 induced acute hepatotoxicity in murine model.
Pdf carbon tetrachloride ccl4 induced hepatotoxicity in. Age is a risk factor for druginduced liver injury dili. Substance name carbon tetrachloride casrn 56235 last revised 03312010 the rfd is an estimate with uncertainty spanning perhaps an order of magnitude of a daily oral exposure to the human population including sensitive subgroups that is likely to be without an appreciable risk of deleterious effects during a lifetime. Carbon tetrachloride ccl4induced hepatotoxicity is one of the most investigated hepatic injuries, especially in experimental animal models.
O, onikanni a, sabiu saheed abstract the present study was carried out to evaluate the hepatoprotective effects of aqueous extract of. Protective effects of puerarin on carbon tetrachloride. Protective effect of ricinus communisleaves extract on carbon tetrachloride induced hepatotoxicity in albino rats evan sabina princea, poorna parameswarib, rasool mahaboob khanc, aschool of biotechnology, chemical and biomedical engineering, vit university, vellore 632 014, india. Hepatocellular damage by reactive carbon tetrachloride metabolites. Nigella sativa seeds protect against hepatotoxicity and dyslipidemia induced by carbon tetrachloride in mice amina e. Ccl 4 was once widely used as a dry cleaning solvent, precursor to refrigerant synthesis, propellant for aerosol cans, a fire extinguishing liquid, as a solvent for oils, fats, and lacquers, as a grain fumigant and curiously enough, in lava lamps 30, 31. Carbon tetrachloride cci4 was widely employed in human medicine as an anesthetic agent 1.
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