Abstract  The chlorinated methanes, particularly carbon tetrachloride and chloroform, are classic models of liver injury and have developed into important experimental hepatoxicants over the past 50 years. Hepatocellular steatosis and necrosis are features of the acute lesion. Mitochondria and the endoplasmic reticulum as target sites are discussed. The sympathetic nervous system, hepatic hemodynamic alterations, and role of free radicals and biotransformation are considered. With carbon tetrachloride, lipid peroxidation and covalent binding to hepatic constituents have been dominant themes over the years. Potentiation of chlorinated methane-induced liver injury by alcohols, aliphatic ketones, ketogenic compounds, and the pesticide chlordecone is discussed. A search for explanations for the potentiation phenomenon has led to the discovery of the role of tissue repair in the overall outcome of liver injury. Some final thoughts about future research are also presented.

Abstract  The liver, which is the major organ responsible for the metabolism of drugs and chemicals, is also the primary target organ for many toxic chemicals. Increasing evidence has indicated that inflammatory processes are intimately involved in chemical-induced hepatotoxic processes, and like other inflammatory diseases, such as autoimmunity, are responsible for producing mediators which can effect liver damage or repair. This review will summarize the authors' current understanding of how inflammatory processes influence hepatic pathology and repair following exposure to established hepatotoxic chemicals including carbon tetrachloride (CCl4), an industrial chemical, and acetaminophen (APAP), a widely used analgesic.

Abstract  Carbon tetrachloride (CCI{4}) is a superfund toxicant (CERCLA Priority #47) that usually escapes into the environment as a gas. or it is sometimes found in water and soil. The liver is a primary target of the toxicity of CCI4. Exposure to high levels of CCI{4} induces liver damage, inflammation and fibrosis. In healthy people CCI{4} -induced liver injury and fibrosis can reverse when the exposure is discontinued. However, the response of people with underlying liver diseases, such as chronic hepatitis and fatty liver disease, may change, and their livers could be more susceptible to toxicants than healthy livers. Importantly, the health concerns, including chronic liver disease, are often raised regarding vulnerable communities near the Superfund sites. Therefore, the biological response for Superfund toxicants needs to be studied and eariy detection systems need to be developed for identifying these toxicants released into the environment and accumulating in organisms, including the human body. In this context, we will use mouse models with underlying liver diseases, such as Tak1[deltaHEP] mice which have been developed by our laboratory, which mimic human chronic liver disease with liver fibrosis and cancer and mice fed high fat diet that induce obesity and fatty liver disease. Using experimental murine models of liver diseases, we will examine the effect of underlying liver diseases on long-term continuous exposure to CCI{4} with respect to liver fibrosis and cancer. In addition to the evaluation of liver fibrosis by established methodology, we will create a sensitive new detection system for monitoring liver fibrosis using a new fluorescent protein and gene reporter system. This system will also evaluate the effect of another Superfund toxicant in the initiation of liver fibrosis. This project will provide new insights into the effect of environmental CCI{4} exposure on people with underlying liver diseases, including chronic hepatitis and fatty liver. Underlying liver disease is a serious health concern in vulnerable communities, including tribal and low-income border communities that are the targets of our Superfund Research Program. We will share and disseminate our results through the Research Translation and Community Engagement Cores.

Abstract  Carbon tetrachloride (CCI{4}) is a superfund toxicant (CERCLA Priority #47) that usually escapes into the environment as a gas. or it is sometimes found in water and soil. The liver is a primary target of the toxicity of CCI4. Exposure to high levels of CCI{4} induces liver damage, inflammation and fibrosis. In healthy people CCI{4} -induced liver injury and fibrosis can reverse when the exposure is discontinued. However, the response of people with underlying liver diseases, such as chronic hepatitis and fatty liver disease, may change, and their livers could be more susceptible to toxicants than healthy livers. Importantly, the health concerns, including chronic liver disease, are often raised regarding vulnerable communities near the Superfund sites. Therefore, the biological response for Superfund toxicants needs to be studied and eariy detection systems need to be developed for identifying these toxicants released into the environment and accumulating in organisms, including the human body. In this context, we will use mouse models with underlying liver diseases, such as Tak1[deltaHEP] mice which have been developed by our laboratory, which mimic human chronic liver disease with liver fibrosis and cancer and mice fed high fat diet that induce obesity and fatty liver disease. Using experimental murine models of liver diseases, we will examine the effect of underlying liver diseases on long-term continuous exposure to CCI{4} with respect to liver fibrosis and cancer. In addition to the evaluation of liver fibrosis by established methodology, we will create a sensitive new detection system for monitoring liver fibrosis using a new fluorescent protein and gene reporter system. This system will also evaluate the effect of another Superfund toxicant in the initiation of liver fibrosis. This project will provide new insights into the effect of environmental CCI{4} exposure on people with underlying liver diseases, including chronic hepatitis and fatty liver. Underlying liver disease is a serious health concern in vulnerable communities, including tribal and low-income border communities that are the targets of our Superfund Research Program. We will share and disseminate our results through the Research Translation and Community Engagement Cores.

Abstract  Carbon tetrachloride (CCI{4}) is a superfund toxicant (CERCLA Priority #47) that usually escapes into the environment as a gas. or it is sometimes found in water and soil. The liver is a primary target of the toxicity of CCI4. Exposure to high levels of CCI{4} induces liver damage, inflammation and fibrosis. In healthy people CCI{4} -induced liver injury and fibrosis can reverse when the exposure is discontinued. However, the response of people with underlying liver diseases, such as chronic hepatitis and fatty liver disease, may change, and their livers could be more susceptible to toxicants than healthy livers. Importantly, the health concerns, including chronic liver disease, are often raised regarding vulnerable communities near the Superfund sites. Therefore, the biological response for Superfund toxicants needs to be studied and eariy detection systems need to be developed for identifying these toxicants released into the environment and accumulating in organisms, including the human body. In this context, we will use mouse models with underlying liver diseases, such as Tak1[deltaHEP] mice which have been developed by our laboratory, which mimic human chronic liver disease with liver fibrosis and cancer and mice fed high fat diet that induce obesity and fatty liver disease. Using experimental murine models of liver diseases, we will examine the effect of underlying liver diseases on long-term continuous exposure to CCI{4} with respect to liver fibrosis and cancer. In addition to the evaluation of liver fibrosis by established methodology, we will create a sensitive new detection system for monitoring liver fibrosis using a new fluorescent protein and gene reporter system. This system will also evaluate the effect of another Superfund toxicant in the initiation of liver fibrosis. This project will provide new insights into the effect of environmental CCI{4} exposure on people with underlying liver diseases, including chronic hepatitis and fatty liver. Underlying liver disease is a serious health concern in vulnerable communities, including tribal and low-income border communities that are the targets of our Superfund Research Program. We will share and disseminate our results through the Research Translation and Community Engagement Cores.

Abstract  OBJECTIVE: To assess the effect of Danshen on liver regeneration capacity of carbon tetrachloride-induced liver injury rats.

METHOD: Computer retrieval of data from CJFD, CBM, Chinese science & technology journal full-text database and Chinese medical association digital journals, and such foreign databases as PubMed, EMBASE and SCI was included in the randomized controlled trials (RCT) of rat liver injury induced by carbon tetrachloride,with the search as at May 2012. A Meta analysis was made using Rev-Man 5.1 software. Using the GRADE system to addess five outcomes in stuay.

RESULT: Two hundred and fourteen rats got involved in seven randomized trials. Meta analysis showed there were statistical differences between the Danshen group and the control group in alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-alpha) and hyaluronic acid (HA) after rat liver injury induced by carbon tetrachloride. When we used system to each outcome, because of serious limitations and indirect, they are all very low quality.

CONCLUSION: Danshen shows certain promoting effect to liver regeneration in carbon tetrachloride-induced liver injury rats.

Abstract  Carbon tetrachloride is extensively used as a solvent in dry cleaning, degreasing, and fat extraction, because of its low cost and non- inflammability; it is also used in fire extinguishers. An extensive series of experi ments are described in which guineapigs, rats and monkeys were exposed to known concentra tions of vapour for 8 hours a day, 5 days a week, for 101/2 months: some animals received 225 exposures. With severe exposures the liver was attacked with fatty degeneration, advancing to typical fibrotic hobnail liver, if the exposure was continued. The kidneys and adrenals were also similarly damaged. If, however, the exposures were not extreme, but were continued, the damaged cells rapidly re generated, when the new cells were more resistant than normal to the vapour. Guinea- pigs were less resistant than rats and monkeys. A number of observations were made of occupa tional conditions of men at work: and 96 men exposed to carbon tetrachloride in industry were studied. The conclusions arrived at are that vapour concentrations of 100 per million are safe for continuous exposure at work, that 1, 000 per million is safe for half an hour a day, and that under reasonable conditions of ventilation and care men increase their resistance with exposure. Men exposed to risk should be medically examined at least twice a year, when determinations should be made of icteric index, blood calcium and visual fields: differential white cell counts should also be made. With intelligent super vision no worker need be injured by carbon tetrachloride. E. L. Collis.

Abstract  National-scale emissions of carbon tetrachloride (CCl4) are derived based on inverse modeling of atmospheric observations at multiple sites across the United States from the National Oceanic and Atmospheric Administration's flask air sampling network. We estimate an annual average US emission of 4.0 (2.0-6.5) Gg CCl4 y(-1) during 2008-2012, which is almost two orders of magnitude larger than reported to the US Environmental Protection Agency (EPA) Toxics Release Inventory (TRI) (mean of 0.06 Gg y(-1)) but only 8% (3-22%) of global CCl4 emissions during these years. Emissive regions identified by the observations and consistently shown in all inversion results include the Gulf Coast states, the San Francisco Bay Area in California, and the Denver area in Colorado. Both the observation-derived emissions and the US EPA TRI identified Texas and Louisiana as the largest contributors, accounting for one- to two-thirds of the US national total CCl4 emission during 2008-2012. These results are qualitatively consistent with multiple aircraft and ship surveys conducted in earlier years, which suggested significant enhancements in atmospheric mole fractions measured near Houston and surrounding areas. Furthermore, the emission distribution derived for CCl4 throughout the United States is more consistent with the distribution of industrial activities included in the TRI than with the distribution of other potential CCl4 sources such as uncapped landfills or activities related to population density (e.g., use of chlorine-containing bleach).

Abstract  This document presents background information and justification for the Integrated Risk Information System (IRIS) Summary of the hazard and dose-response assessment of carbon tetrachloride. IRIS Summaries may include oral reference dose (RfD) and inhalation reference concentration (RfC) values for chronic and other exposure durations, and a carcinogenicity assessment. The RfD and RfC, if derived, provide quantitative information for use in risk assessments for health effects known or assumed to be produced through a nonlinear (presumed threshold) mode of action. The RfD (expressed in units of mg/kg-day) is defined as an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. The inhalation RfC (expressed in units of mg/m3) is analogous to the oral RfD, but provides a continuous inhalation exposure estimate. The inhalation RfC considers toxic effects for both the respiratory system (portal of entry) and for effects peripheral to the respiratory system (extrarespiratory or systemic effects).

Abstract  Pheochromocytomas are tumors originating from chromaffin cells of the adrenal medulla, which have been observed in numerous carcinogenicity studies. The authors have evaluated pheochromocytoma concurrence with other effects and the possible mechanisms, in order to assess the relevance of such data for the classification of carcinogenic effects and their relevance to humans. The evaluation revealed that pheochromocytomas occur with relatively higher frequency in male rats, especially when the following conditions are involved: hypoxia, uncoupling of oxidative phosphorylation, disturbance in calcium homeostasis, and disturbance of the hypothalamic endocrine axis. The underlying biochemical mechanisms suggest that other substances that interfere with these biochemical endpoints also produce pheochromocytomas. Such endpoints include enzymes involved in catecholamine synthesis, receptor tyrosine kinase (RET), hypoxia-inducible factor (HIF), succinate dehydrogenase, fumarate hydratase, and pyruvate dehydrogenase. To date, there is no indication that the substances inducing pheochromocytomas in animal experiments also induce corresponding tumors in humans. Because the mechanisms of action identified in rats are to be expected in humans, pheochromocytomas may be induced after exposure conditions similar to those used in the animal studies. Whether hereditary mutations represent a risk factor in humans is not clear. Pheochromocytomas that occur in animal experiments currently appear to have little relevance for conditions at the work place. When sufficiently documented and evaluated, such secondary pheochromocytomas are not relevant for classification and human risk assessment.

Abstract  The incubation of isolated rat hepatocytes with 0.172 mM carbon tetrachloride caused a rapid decrease in the calcium content of both mitochondrial and extramitochondrial compartments. However, the release of Ca2+ from the intracellular stores was not associated with an increase in the cytosolic Ca2+ levels as measured by activation of phosphorylase alpha or by Quin-2 fluorescence. A rapid rise in hepatocyte free calcium was only observed with concentrations of CCl4 higher than 0.172 mM. The lack of activation of phosphorylase alpha was not due to the inhibition of the enzyme by CCl4, since in CCl4-treated hepatocytes the phosphorylase activity could be stimulated by glucagon, butyryl--cAMP or by the increase of cell calcium induced by the addition of A23187. Ca2+-dependent ATPase of plasma membranes was only slightly affected in the early phases of poisoning with CCl4 when both mitochondrial and extramitochondrial calcium pools were already lowered. This led to the conclusion that calcium released from intracellular organelles could be extruded from the cells in sufficient amounts to prevent the increase of the cytosolic levels. A rise in hepatocyte free calcium was observed during the second hour of incubation with CCl4, concomitantly with the appearance of both LDH leakage and plasma membrane blebbing. The addition of EGTA to the medium prevented both the increase in cytosolic Ca2+ and the blebbing suggesting that they were a consequence of an influx of calcium into the cells. However, neither EGTA nor the addition of inhibitors of calcium-dependent phospholipase A2 or non-lysosomal proteases were able to protect against cell death. These latter results suggested that the alterations of calcium distribution induced by CCl4 in isolated hepatocytes were not a primary cause of the toxic effects, although they did not exclude that a sustained rise in cytosolic Ca2+ could contribute in the progression of cell injury.

Abstract  The review presents the modern concepts on biochemical mechanisms of processes, that result in comatose states (CS), with emphasis on the search of new therapeutic approaches. CS of various origin causes severe suppression of brain cells functioning and stable unconsciousness. Numerous reasons of various CS are classified into two main groups: primary brain damages (ischemia, tumor, trauma) and secondary damages originating from system injuries in the body (endocrine, toxic e. c.). The most often primary CS is the hypoxic-ischemic one, as result of corresponding encephalopathy. Its mechanism is the brain cells "energy crisis"--because of decreased blood supply or its deficiency by energy substrates or/and by oxygen. Among secondary CS the substantial place takes hepatic coma as a consequence of hepatic encephalopathy in severe liver diseases--cirrhosis, acute liver failure, sharp intoxication. Its main reason is associated with exess of ammonia entering the brain tissue (it accumulates in blood because of lack of its removing by damaged hepatocytes). Ammonia reacts with glutamate in brain astrocytes and the product of this reaction, glutamine, induced osmotic imbalance, that results in change of form and functions of these important brain cells. It induces, in turn, neurons functions damages, changes in neurotransmission and cerebral blood flow and all these may give rise CS. The most of CS studies are carried out in human. Experimental models ofhepatic CS are reproduced mainly in rats, the most often by surgery methods. Other models included administration of thioacetamide or D-galactosamine, sometimes in combination with lipopolysaccharide. In earlier studies ammonia administration together with liver damages by ligation or by CCl4 was used. The main principles of hepatic coma treatment include the care of encephalopathy, detoxification, and liver treatment. Elaboration of new nanodrugs with increased penetration into tissues and cells, in particular, on the base of phospholipid nanoparticles, may increase substantially the therapeuti efficiency. One of such drug is thought to be a new hepatoprotective preparation phosphogliv--nanoparticles of soy phosphatidylcholine with glycyrrhizic acid. It is supposed, that the further development of phospholipid nanoforms, with minimal particle sizes, may reveal the more action in CS treatment.

Abstract  In this work structural behavior of apo form of the adenosine A2A receptor in the implicit membrane-mimicking environment was investigated by means of molecular dynamics (MD) technique. For better interpretation of the obtained data they were analyzed using principal components analysis. The principal components analysis technique was applied to both MD snapshots as well as X-ray structures of the adenosine receptor. As the result the charts were obtained which reflected an interconnection interdependence between dynamic behavior of the receptor observed on the MD trajectories as well as experimental dataset of investigated protein. The calculated MD trajectories allow to observe represent pronounced structural dynamics of the A2A receptor especially in the intracellular part loop connecting TM 5 and 6 of that protein. This observation generally corresponds to the dynamic behavior of the investigated protein seen on the experimental dataset. Therefore the pattern of the intramolecular motions might be following directly from the spatial architecture (fold) of the receptor under study.

Abstract  The dissipative concentration test of VOCs in the remediation process of a typical contaminated site was operated, and three routes of exposure were set up for health risk assessment in the repair process. Analysis showed that carbon tetrachloride was the single pollutant with highest multi-route cumulative non-carcinogenic index, which was as high as 8.86E + 01, and its contribution rate to the integrated non-carcinogenic effects was 74.45%. Respiratory exposure was the exposure route with highest multi-pollutant hazard index, which was 1.01E + 02, accounting for 84. 87% of the comprehensive risk index, and the index of integrated non-carcinogenic damage was 1.19E + 02. 1,2-dichloroethane was the single pollutant with highest multi-route cumulative carcinogenic index, which was as high as 3.08E-02, and its contribution rate to the integrated carcinogenic effects was 69.53%. Respiratory exposure was the exposure route with highest multi-pollutant hazard index, which was 3.96E -02, accounting for 89.39% of the comprehensive risk index, and the index of integrated carcinogenic damage was 4.43E-02.

Abstract  Both experimental animals and humans exhibit complex cellular responses upon exposure to xenobiotics and may undergo similar types of metabolic changes leading to adverse outcomes. Exposure to xenobiotics results in perturbation of many cellular events (e.g. oxidative stress, lipid peroxidation, inflammation, genotoxicity, cytotoxicity, etc.), and during this process biochemicals (endogenous metabolites) of a given metabolic pathway are increased, decreased or unaffected. Metabolomics is an emerging medium to high-throughput technology that can automatically identify, quantify and characterize hundreds to thousands of low molecular weight biochemicals simultaneously, using targeted or global analytical approaches, yielding a metabolic fingerprint and understanding of biochemical pathway perturbations. Herein, we illustrate how metabolomics can be utilized to explore the mechanisms of action of xenobiotics which affect different 'key events' contributing to different mode(s) of action. The extensively studied hepatotoxicant carbon tetrachloride (CCl(4)) is specifically described.

Abstract  The present report is the committee's 18th interim report. It summarizes the committee's conclusions and recommendations for improving NAC's AEGL documents for 25 chemicals: allyl alcohol, bis-chloromethyl ether, chloromethyl methyl ether, bromine pentafluoride, bromine trifluoride, chlorine pentafluoride, carbon tetrachloride, chloroform, chlorosilanes (26 selected compounds), epichlorohydrin, formaldehyde, hydrogen bromide, hydrogen iodide, methyl bromide, methyl chloride, nitric acid, nitric oxide, nitrogen dioxide, nitrogen tetroxide, piperidine, titanium tetrachloride, toluene, trimethylbenzenes (1,2,4-; 1,2,5-;and 1,3,5-TMB), vinyl acetate monomer, and vinyl chloride.

Abstract  Toxicogenomics is a rapidly developing discipline focused on the elucidation of the molecular and cellular effects of chemicals on biological systems. As a collaborative study group of Toxicogenomics/JEMS·MMS, we conducted studies on hepatocarcinogens in rodent liver in which 100 candidate marker genes were selected to discriminate genotoxic hepatocarcinogens from non-genotoxic hepatocarcinogens. Differential gene expression induced by 13 chemicals were examined using DNA microarray and quantitative real-time PCR (qPCR), including eight genotoxic hepatocarcinogens [o-aminoazotoluene, chrysene, dibenzo[a,l]pyrene, diethylnitrosamine (DEN), 7,12-dimethylbenz[a]anthracene, dimethylnitrosamine, dipropylnitrosamine and ethylnitrosourea (ENU)], four non-genotoxic hepatocarcinogens [carbon tetrachloride, di(2-ethylhexyl)phthalate (DEHP), phenobarbital and trichloroethylene] and a non-genotoxic non-hepatocarcinogen [ethanol]. Using qPCR, 30 key genes were extracted from mouse livers at 4 h and 28 days following dose-dependent gene expression alteration induced by DEN and ENU: the most significant changes in gene expression were observed at 4 h. Next, we selected key point times at 4 and 48 h from changes in time-dependent gene expression during the acute phase following administration of chrysene by qPCR. We successfully showed discrimination of eight genotoxic hepatocarcinogens [2-acetylaminofluorene, 2,4-diaminotoluene, diisopropanolnitrosamine, 4-dimethylaminoazobenzene, 4-(methylnitsosamino)-1-(3-pyridyl)-1-butanone, N-nitrosomorpholine, quinoline and urethane] from four non-genotoxic hepatocarcinogens [1,4-dichlorobenzene, dichlorodiphenyltrichloroethane, DEHP and furan] using qPCR and principal component analysis. Additionally, we successfully identified two rat genotoxic hepatocarcinogens [DEN and 2,6-dinitrotoluene] from a nongenotoxic-hepatocarcinogen [DEHP] and a non-genotoxic non-hepatocarcinogen [phenacetin] at 4 and 48 h. The subsequent gene pathway analysis by Ingenuity Pathway Analysis extracted the DNA damage response, resulting from the signal transduction of a p53-class mediator leading to the induction of apoptosis. The present review of these studies suggests that application of principal component analysis on the gene expression profile in rodent liver during the acute phase is useful to predict genotoxic hepatocarcinogens in comparison to non-genotoxic hepatocarcinogens and/or non-carcinogenic hepatotoxins.

Abstract  Infused (transplanted) green fluorescent protein (GFP)-positive bone marrow cells (BMCs) migrated into the peri-portal regions of the cirrhotic mouse liver induced continuous CCl4 injection without irradiation (without bone marrow ablation). The infused GFP-positive BMCs differentiated into hepatoblasts detected with Liv2-antibody and then differentiated into albumin-producing hepatocytes. The differentiation "niche" induced by persistent liver damage due to continuous CCl4 injection seems to be an essential factor. Microarry analysis showed that at an early stage after BMC infusion through mouse tail vein, the genes related to degradation of extracellular matrix (ECM) e.g. MMP-9 were activated. BMC infusion improved liver fibrosis and the survival rate. Recent our finding indicates that mesencymal bone marrow cells will differentiate to hepatocytes and FGF2 will accelerate this differentiation of BMC to hepatocyte. Based on the results obtained in basic research using the GFP/CCl4 model, human trials are now undergoing. We have done this autologous bone marrow cell infusion therapy for 19 patients with advanced liver cirrhosis. The clinical study of liver cirrhosis (LC) cases that underwent autologous bone marrow cell infusion from peripheral vein is as follows. Subjects were LC patients with T.B. of < 3.0 mg/dl, Plt of > 5(10(10)/l) and no viable hepatocellular carcinoma by diagnostic imaging. Autologous bone marrow cells (BMCs, 400 ml) were isolated from the ilium under general anesthesia. BMCs were separated by cell washing and were infused via the peripheral vein. After BMC infusion, liver function was monitored by blood examination for 24 weeks. We could follow 9 cases more than 6 months so far. After washing, 5.20 +/- 0.63 x 10(9) BMCs were infused into LC patients. Serum albumin level and total protein were significantly improved at 24 weeks after BMC infusion (p < 0.05). The Child-Pugh score was significantly improved at 4 week and 24 weeks after BMC infusion (p < 0.05). No major adverse effects were noted. In conclusion, autologous BMC infusion might be considered as a novel treatment for advanced LC patients.

Abstract  Antioxidants of natural origin are considered as possible agents for prevention and treatment of liver diseases. Marine algae and in particular their extracts and obtained from them sulfated polysaccharides are significant sources of natural antioxidants. The recent data on the effect of the extracts and sulfated polysaccharides of seaweed on the functional activity of the liver with injuries induced by CCl4, some drugs (paracetamol, diclofenac), N-nitrosocompounds, aflatoxin are presented in the review. Particular attention is paid to the effect of sulfated polysaccharides and in particular fucoidans on the functional activity of the liver in patients with chronic viral hepatitis C. Fucoidan is highly safe and active not only as an antioxidant but also as an inhibitor of HCV replication, has antiinflammatory and immunomodulating effects. The data of the review allow to conclude that seaweed extracts and sulfated polysaccharides may be a basis for development of new generation drugs in the future for the treatment and prevention of liver diseases.