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. Hepatic injury can be induced by the administration of carbon tetrachloride ccl4 via the production of free radicals. 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. The problem formulation document will be available for comment until august 16, 2018 in the docket epahqoppt20160733. Three groups of 10 rats each were subjected to experimental study. 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.
Hepatotoxicity was induced in vivo by administering ccl 4 to rats that had undergone a 68% partial hepatectomy ph. Carbon tetrachloride is most often found in the air as a colorless gas. Hepatoprotective mechanisms of taxifolin on carbon tetrachloride. Mechanism of carbon tetrachloride induced hepatotoxicity. 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. Hepatoprotective efffect of a wild edible mushroom on carbon tetrachloride induced hepatotoxicity in mice. 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. 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. Studies on the mechanism of glutathione prevention of. All atsdr toxicological profile pdf files are electronic conversions from paper copy or other electronic ascii text files. Pdf carbon tetrachloride ccl4 induced hepatotoxicity in. Protection against carbon tetrachloride induced hepatotoxicity by protein a. Mechanism of carbon tetrachlorideinduced hepatotoxicity.
Human symptoms of acute shortterm inhalation and oral exposures to carbon tetrachloride include headache. Protective effect of secoisolariciresinol diglycoside in. 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. 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. Species differences in carbon tetrachlorideinduced hepatotoxicity. The primary effects of carbon tetrachloride in humans are on the liver, kidneys, and central nervous system cns. 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. Hepatic toxicity in rats exposed to carbon tetrachloride by inhalation or by. Carbon tetrachloride 56235 hazard summary carbon tetrachloride may be found in both ambient outdoor and indoor air. It has also been used as a cleaning fluid in the dry cleaning industry, as. Carbon tetrachloride iarc 1999a and chloroform iarc 1999b are hepatotoxic chemicals that increase liver neoplasms in mice. Hepatoprotective and antioxidant activity of bombax ceiba. Research article asian journal of biomedical and pharmaceutical sciences 1 3 2011, 2631 corresponding author.
Potentiation of carbon tetrachloride hepatotoxicity by. Acute carbon tetrachloride poisoning in 19 patients. Carbon tetrachloride is used to make refrigeration fluid and propellants for aerosol cans. Return to the risk evaluation page for carbon tetrachloride. Hepatotoxicity induced by carbon tetrachloride was reflected by a marked elevation of ast and alt activities, and histopathologic alterations. 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. Sitosterol protects against carbon tetrachloride hepatotoxicity but not gentamicin nephrotoxicity in rats via the induction of mitochondrial glutathione redox cycling. However, there is a limited understanding of pediatric dili. Carbon tetrachloride ccl 4 is the most perceived chemical substance utilized in developing models of hepatic damage. Here, 2weekold weaning and 8weekold adult male icr mice were intraperitoneally injected with ccl4 0.
Antioxidant potential of xylopia aethiopica adewale o. The most recent work in this field has inaugurated a third revolution in the study of. The role of alcohol metabolism in 2butanolinduced potentiation of carbon tetrachloride ccl4 hepatotoxicity was studied in rats. Ccl 4 has become a model for the study of agents that cause localized cellular injury via a freeradical mechanism.
Carbon tetrachloride an overview sciencedirect topics. Female swiss albino mice were supplied with larginine for 6 days orally, 200 mgkg body weight prior or post to hepatic injury induction. Formerly used as a drycleaning solvent, carbon tetrachloride has been almost entirely displaced from this application by tetrachloroethylene, which is. Metformin met is a potent antidiabetic and redox modulatory agent that has shown anticancer and protective effects on various organs.
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. Hederin on carbon tetrachlorideinduced hepatotoxicities were investigated in mice. This monograph is one in a series of selfinstructional. Pdf hepatoprotective activity of methanol extract of. Introduction carbon tetrachloride ccl 4 is an important model agent to study the pathogenesis of liver injury boll et al. This article is an attempt to summarize the current understanding of hepatotoxicity of antidiabetic drugs. Hepatotoxicity of trichloroethylene carbon tetrachloride. Hepatotoxicity did not receive as much attention as other prevalent complications i. 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. Formation of novel noncyclooxygenasederived prostanoids f2isoprostanes in carbon tetrachloride hepatotoxicity. Abstract background hepatotoxicity induced by carbon tetrachloride ccl4 is used as an experimental model to screen phytochemicals with liver protecting activity. The hypothesis that ccl4 poisoning exerts its hepatotoxic action via adrenalmedullary discharge of catecholamines and stimulation of sympathetic autonomic.
Pdf hepatoprotective effect of cleome gynandra on carbon. It is also called carbon chloride, methane tetrachloride, perchloromethane, tetrachloroethane, or benziform. This effect of ccl4 appears to be reversible and dosedependent. 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. It is a colourless liquid with a sweet smell that can be detected at low levels. It is a known animal carcinogen and a potential human carcinogen. 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. 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. 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 ccl 4, a volatile inorganic compound, is a very welldescribed hepatotoxicant. 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. Protective effect of ricinus communis leaves extract on. Carbon tetrachloride, when injected directly into the portal venous cannula of an isolated perfused rat liver, inhibited the net outward transport of hepatic triglycerides. If the inline pdf is not rendering correctly, you can download the pdf. Hepatoprotective effect of cleome gynandra on carbon. Carbon tetrachloride ccl4 the journal of phytopharmacology. Carbon tetrachloride hepatotoxicity pharmacological.
It is a clear liquid with a sweet smell that can be detected at low levels. Treatment of carbon tetrachloride poisoning with hyperbaric. Cleome gynandra has been used widely in indian indigenous system. 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. Toxicity was determined by increases in serum sorbitol dehydrogenase and alanine aminotransferase activities measured 24 hr following the treatments. Department of health and human services, public health service. Experimental liver fibrosis in mice can be induced by surgical intervention e. Protective effects of propolis and probiotic lactobacillus acidophilus against carbon tetrachlorideinduced hepatotoxicity in rats. Carbon tetrachloride induces hepatotoxicity via oxidative stress and inflammation. You may need a pdf reader to view some of the files on this page. Hepatotoxicity and mechanism of action of haloalkanes.
Elzergy1 1 department of zoology, faculty of science, alexandria university, alexandria, egypt. Integrated risk information system iris march 2010. Effects of pharmaceutical formulations containing thyme on. 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. It is known to cause damage to the liver, lungs, adrenals, and central nervous system in humans and. Susceptibility to chlordeconecarbon tetrachloride induced.
Carbon tetrachloride was purchased from sigma, aldrich. Riboflavin reduces carbon tetrachloride induced increase in tnf riboflavin, a component of flavoproteins plays an important role in hepatoprotection. Role of nigella sativa in carbon tetrachloride induced. Carbon tetrachloride ccl 4induced hepatic damage in experimental sprague dawley rats. Introduction carbon tetrachloride ccl 4 has been used as a dry cleaning agent, fabric spotting fluid, solvent, reagent in chemical. Animals were sacrificed at various times after the administration of 2butanol 2. Nigella sativa seeds protect against hepatotoxicity and dyslipidemia induced by carbon tetrachloride in mice amina e. Carbon tetrachloride, hepatoprotective, hepatotoxicity, nigella sativa. 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. The most recent work in this field has inaugurated a third revolution in the study of carbon tetrachloride hepatotoxicity. Carbon tetrachloride, also known by many other names such as 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. Pdf protection against carbon tetrachlorideinduced. In the present case, we have evidence of ingestion a quantity of carbon tetrachloride well in excess of the minimum lethal dose.
Concomitant treatment of rats with a nonhepatotoxic dose of dichloromethane 6 mmolkg, ip significantly potentiated the hepatotoxicity of carbon tetrachloride 2 mmolkg, ip. The present work was initiated to investigate the kidney response to hepatic injury induced by ccl4 and its treatment by larginine. 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. Effect of curcumin and its analogue on lipids in carbon. Hepatocellular damage by reactive carbon tetrachloride metabolites. Carbon tetrachloride ccl 4 is regarded as highly toxic. 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. 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. Pdf influence of liv52 on carbon tetrachloride induced.
The carbon tetrachloride model in mice d scholten, j. Amelioration of ccl4 induced liver injury in swiss albino. Carbon tetrachloride ccl 4 is widely used for experimental induction of liver damage5. Carbon tetrachloride ccl4 metabolism via cytochrome p450 leads to. Get a printable copy pdf file of the complete article 1. The present study was aimed to evaluate the efficacy of s. This free radical then initiates lipid peroxidation with subsequent destruc. Carbon tetrachloride ccl 4 is a wellknown and widely used model for induced liver injury studies mir et al. Carbon tetrachlorideinduced hepatotoxicity in rat is. Carbon tetrachlorideinduced hepatotoxicity request pdf.
In acute inhalation studies, animals exposed to high doses 46001200 ppm of carbon tetrachloride experienced stupor, incoordination, and unconsciousness. Combination of metformin and luteolin synergistically. In vitro studies were also performed in hepatocytes isolated from ph rats. Riboflavin attenuates carbon tetrachloride induced oxidative stress.
The prevention of carbon tetrachlorideinduced hepatotoxicity. 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. 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. The carbon tetrachloride model in mice the authors 2015. Liver diseases are one of the fatal disorders due to the vital role of the liver. Abdominal films con cci, 1 lngesllon ypeboctreoi 11 mei7 1111 ii 14 i i 1 11. The present study was designed to evaluate the role of liv52 in carbon tetrachloride induced liver toxicity. If the inline pdf is not rendering correctly, you can download the pdf file here. Pdf hepatoprotective efffect of a wild edible mushroom on. Carbon tetrachloride is a manufactured chemical that does not occur naturally. Carbon tetrachloride is a clear, nonflammable liquid which is almost insoluble in water. Hydrolysis of phosgene would then result in the formation of co 2, a major in vivo and in vitro metabolite of carbon tetrachloride. Age is a risk factor for druginduced liver injury dili.
The hepatotoxic effects of ccl 4 in the rat were determined in a time and doseresponse study. Protection of regenerating liver after partial hepatectomy. Sep 26, 2019 toxicological profile for carbon tetrachloride. Pdf solanum nigrum is used in hepatic disorders in folk medicines. 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. Carbon tetrachloride cci4 was widely employed in human medicine as an anesthetic agent 1. Cbl was evaluated on ccl4 induced acute hepatotoxicity in murine model. Pdf carbon tetrachloride ccl4 induced hepatotoxicity in rats.
Dichloromethane potentiation of carbon tetrachloride. Various medicinal plants have been used to treat for. Carbon tetrachloride ccl4induced hepatotoxicity is one of the most investigated hepatic injuries, especially in experimental animal models. Carbon tetrachloride problem formulation assessing and. In the present study the hepatoprotective effect of methonolic extract of c. Potentiation of carbon tetrachloride hepatotoxicity and lethality in type 2 diabetic rats. Protective effects of puerarin on carbon tetrachloride. Carbon tetrachloride ccl 4 is well known to induce hepatotoxicity after being metabolized to trichloromethyl free radical ccl 3 by cyp2e1. 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. Carbon tetrachlorideinduced liver injury in the rabbit. Hepatotoxicity was induced in rats by carbon tetrachloride ccl 4 treatment. Pdf carbon tetrachloride ccl4 induced hepatotoxicity. Carbon tetrachloride ccl4induced hepatic damage in.
Protective effects of propolis and probiotic lactobacillus. Ccl 4 is a biologically inactive and stable substance that is chemically. Nigella sativa seeds protect against hepatotoxicity and. Hepatotoxicity was assessed by estimating the activities of marker enzymes and by histological studies. The effect of skf 525a on the distribution of carbon tetrachloride in rats. Weaning mice and adult mice exhibit differential carbon. Carbon tetrachloride is a liquid carbon tetrachloride is a manufactured clear liquid with a sweet odor that evaporates easily. 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. Abdelkader oumeddour 1,2, djahida zaroure 2, raziqua haroune 2, rima zaimeche 2, karima riane 3. Carbon tetrachlorideinduced hepatotoxicity in pregnant and. Protection by 2diethylaminoethyl2,2diphenylvalerate hydrochloride against carbon tetrachloride hepatotoxicity. Carbon tetrachloride ccl4 creates necrosis in hepatocytes. O, onikanni a, sabiu saheed abstract the present study was carried out to evaluate the hepatoprotective effects of aqueous extract of. 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.
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