tannins and Chemical-and-Drug-Induced-Liver-Injury

Topics: Animals; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemistry; Coffee; Contrast Media; Drug Contamination; Food Additives; Humans; Intestinal Absorption; Kidney Diseases; Rats; Tannins; Tea

Topics: Animals; Arsenicals; Chemical and Drug Induced Liver Injury; Chloroform; Chlorpromazine; Contraceptives, Oral; Drug Hypersensitivity; Humans; Isoniazid; Liver Diseases; Steroids; Tannins; Tetracycline

Several chemicals and medications induce cellular damage in various organs of the body by activating reactive substances' metabolism leading to various pathological conditions including liver disease. In this study, we evaluated the prophylactic and curative effects of Carica papaya Linn. pulp water extract (PE) against CCl

Topics: Animals; Antioxidants; Carbon Tetrachloride; Carica; Chemical and Drug Induced Liver Injury; Fibrosis; Flavonoids; Inflammation; Lipid Peroxidation; Liver; Male; Oxidative Stress; Plant Extracts; Rats; Tannins

Exposure to crude acetylene can occur in occupational settings. This study assessed the modulatory activities of selected polyphenols on the hematotoxic, cardiotoxic, and hepatotoxic effects of crude acetylene. Wistar rats were exposed to 58 000 ppm crude acetylene for 10 min at 12 h intervals for 30 days. Some exposed groups were treated with 50 mg/kg rutin, quercetin, gallic acid, or tannic acid. Indices of hematological disorder, oxidative stress, and cardiovascular and hepatocellular injuries were evaluated in animals. The results showed a decrease in the levels of hematological indices in crude acetylene-exposed animals except for white blood cell count which was increased. Decreased activity/level of reduced glutathione, superoxide dismutase and ferric reducing antioxidant power with increased lipid peroxidation was observed in animals exposed to crude acetylene. Activities of transaminases, γ-glutamyl transpeptidase, and level of bilirubin were increased while the plasma albumin level was decreased. Dyslipidemia, increased activities of lactate dehydrogenase and creatine kinase-MB, and severe histopathological damage to hepatic and cardiac tissues were also observed in animals exposed to the gas. These deleterious hematological, biochemical, and histopathological changes were ameliorated in crude acetylene-toxified rats treated with the polyphenols. Tannic acid exhibited better activity than gallic acid while quercetin showed a superior activity to rutin. The results indicate that exposure to crude acetylene can lead to blood, heart, and liver-related diseases and dietary polyphenols could provide protective benefits.

Topics: Acetylene; Animals; Antioxidants; Chemical and Drug Induced Liver Injury; Gallic Acid; Lipid Peroxidation; Liver; Oxidative Stress; Polyphenols; Quercetin; Rats; Rats, Wistar; Rutin; Superoxide Dismutase; Tannins

The present study was performed to investigate the protective effects of tannic acid (TA) on liver injury induced by arsenic trioxide (ATO) and to elucidate the mechanism involved as related to the Kelch‑like ECH‑associated protein 1 (Keap1)‑nuclear factor erythroid 2‑related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. Adult rats were intraperitoneally injected with TA, while ATO was administered 1 h later. On the 11th day, the rats were euthanized to determine any liver histological changes, liver function, and the activities of antioxidant, antiapoptosis and proinflammatory cytokines in the liver. Furthermore, the protein expression levels of nuclear Nrf2, total Nrf2, Keap1, Heme oxygenase‑1 (HO‑1), NADPH quinine oxidoreductase‑1 (NQO1), and γ‑glutamylcysteine synthetase (γ‑GCS) were determined using western blot analysis. The results showed that TA treatment ameliorated ATO‑induced liver histological changes and decreased the ATO‑induced increased alanine aminotransferase (ALT) and aspartate transaminase (AST) serum levels. Activities of the antioxidant enzymes significantly were increased, while the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were attenuated following TA treatment. In addition, TA treatment inhibited ATO‑induced liver apoptosis and inflammatory responses, increased Bcl‑2 protein expression level and reduced the levels of Bax, caspase‑3, interleukin (IL)‑1β, IL‑6 and tumor necrosis factor (TNF)‑α. Furthermore, TA treatment increased the protein expression levels of Nrf2 and Keap1, HO‑1, NQO1 and γ‑GCS. The results demonstrated that TA has a protective effect on ATO‑treated hepatic toxicity and that its underlying mechanism could be due to TA activation of the Keap1‑Nrf2/ARE signaling pathway, to reduce oxidative stress, apoptosis and inflammation in ATO‑intoxicated rats.

Topics: Animals; Antioxidant Response Elements; Apoptosis; Arsenic Trioxide; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Humans; Inflammation; Injections, Intraperitoneal; Kelch-Like ECH-Associated Protein 1; Liver; Liver Function Tests; Male; NF-E2-Related Factor 2; Oxidative Stress; Rats; Signal Transduction; Tannins

Tannic acid (TA), a water soluble natural polyphenol with 8 gallic acids groups, is abundantly present in various medicinal plants. Previously TA has been investigated for its antimicrobial and antifungal properties. Being a large polyphenol, TA chelates more than 1 metal. Hence TA has been explored for potent antioxidant activities against reactive oxygen species (ROS), reactive nitrogen species (RNS) and as iron chelator in vitro thereby mitigating iron-overload induced hepatotoxicity in vivo. Iron dextran was injected intraperitoneally in Swiss albino mice to induce iron-overload triggered hepatotoxicity, followed by oral administration of TA for remediation. After treatment, liver, spleen, and blood samples were processed from sacrificed animals. The liver iron, serum ferritin, serum markers, ROS, liver antioxidant status, and liver damage parameters were assessed, followed by histopathology and protein expression studies. Our results show that TA is a prominent ROS and RNS scavenger as well as iron chelator in vitro. It also reversed the ROS levels in vivo and restricted the liver damage parameters as compared to the standard drug, desirox. Moreover, this natural polyphenol exclusively ameliorates the histopathological and fibrotic changes in liver sections reducing the iron-overload, along with chelation of liver iron and normalization of serum ferritin. The protective role of TA against iron-overload induced apoptosis in liver was further supported by changed levels of caspase 3, PARP as well as Bax/BCl-2 ratio. Thus, TA can be envisaged as a better orally administrable iron chelator to reduce iron-overload induced hepatotoxicity through ROS regulation.

Topics: Animals; Antioxidants; Chemical and Drug Induced Liver Injury; Iron; Iron Chelating Agents; Iron Overload; Liver; Male; Mice; Plant Extracts; Reactive Oxygen Species; Tannins

Tannic acid (TA) is the polyphenol that has beneficial health effects against oxidative stress. However, the hepatoprotective effects of TA are still relatively unknown. In the present study, we evaluated the effects of TA on an acetaminophen (APAP)-induced hepatotoxicity model, which was established by administration of 400mg/kg of APAP. The levels of alanine transferase (ALT), aspartate transferase (AST), dendothelin-1 (ET-1), nitric oxide (NO) and malondialdehyde (MDA) in the APAP-induced hepatotoxicity mice were significantly increased (up to ~200%), while their levels were reduced by pretreatment with TA (25 and 50mg/kg) (P<0.05). The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in the APAP-induced hepatotoxicity mice were significantly reduced (lower to ~65%), while their activities were increased by pretreatment with TA (25 and 50mg/kg) (P<0.05). In addition, pretreatment with oral TA (25 and 50mg/kg) for 3days before the APAP administration dose-dependently ameliorated changes in hepatic histopathology, suppressed overexpression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), c-fos, c-jun, NF-κB (p65) and caspase-3 (all P<0.05), downregulated bax and upregulated bcl-2, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) (all P<0.05) in the liver. These results indicate that TA exhibits significant hepatoprotective effects against APAP-induced hepatotoxicity and suggest that the hepatoprotective mechanisms of TA may be related to anti-oxidation, anti-inflammation and anti-apoptosis.

Topics: Acetaminophen; Alanine Transaminase; Animals; Anti-Inflammatory Agents; Apoptosis; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Endothelin-1; Heme Oxygenase-1; Humans; Inflammation Mediators; Malondialdehyde; Mice; Mice, Inbred Strains; Nitric Oxide; Oxidative Stress; Superoxide Dismutase; Tannins

We are reporting a rare case of acute liver injury that developed after an internal hemorrhoid treatment with the aluminum potassium sulfate and tannic acid (ALTA) regimen. A 41-year-old man developed a fever and liver injury after undergoing internal hemorrhoid treatment with a submucosal injection of ALTA with lidocaine. The acute liver injury was classified clinically as hepatocellular and pathologically as cholestastic. We could not classify the mechanism of injury. High eosinophil and immunoglobulin E levels characterized the injury, and a drug lymphocyte stimulation test was negative on postoperative day 25. Fluid replacement for two weeks after hospitalization improved the liver injury. ALTA therapy involves injecting chemicals into the submucosa, from the rectum to the anus, and this is the first description of a case that developed a severe liver disorder after this treatment; hence, an analysis of future cases as they accumulate is desirable.

Topics: Adult; Alum Compounds; Chemical and Drug Induced Liver Injury; Fever; Hemorrhoids; Humans; Injections, Intralesional; Lidocaine; Liver; Liver Function Tests; Male; Postoperative Complications; Sclerosing Solutions; Sclerotherapy; Tannins

The present study investigated the hepatoprotective and anti-HBV efficacy of Acacia mellifera (AM) leaves extracts. The crude ethanolic-extract, including organic and aqueous fractions, were tested for cytotoxicity on HepG2 and HepG2.2.15 cells (IC50=684 μg/mL). Of these, the ethyl acetate and aqueous fractions showed the most promising, dose-dependent hepatoprotection in DCFH-toxicated cells at 48 h. In CCl4-injured rats, oral administration of AM ethanol extract (250 and 500 mg/kg·bw) for three weeks significantly normalized the sera aminotransferases, alkaline phosphatase, bilirubin, cholesterol, triglycerides, and lipoprotein levels and elevated tissue nonprotein sulphydryl and total protein. The histopathology of dissected livers also revealed that AM cured the tissue lesions. The phytochemical screening of the fractions showed presence of alkaloids, flavonoids, tannins, sterols, and saponins. Further, anti-HBV potential of the fractions was evaluated on HepG2.2.15 cells. Of these, the n-butanol and aqueous fractions exhibited the best inhibitory effects on HBsAg and HBeAg expressions in dose- and time-dependent manner. Taken together, while the ethyl acetate and aqueous fractions exhibited the most promising antioxidant/hepatoprotective and anti-HBV activity, respectively, the n-butanol partition showed both activities. Therefore, the therapeutic potential of AM extracts warrants further isolation of the active principle(s) and its phytochemical as well as biological studies.

Topics: Acacia; Animals; Antioxidants; Antiviral Agents; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Hep G2 Cells; Hepatitis B virus; Humans; Plant Extracts; Plant Leaves; Rats; Saponins; Tannins

To compare the bidirectional effect of rhubarb total anthraquinone (TA) and total tannins (TT) on rats' liver.. One hundred rats were randomly divided into 10 groups, i.e., the blank group, the model group, the blank + high dose TA group, the blank +low dose TA group, the blank + high dose TT group, the blank + low dose TT group, the model + high dose TA group, the model + low dose TA group, the model +high dose TT group, and the model + low dose TT group, 10 in each group. The carbon tetrachloride (CCI4) was used to prepare the acute liver injury rat model. TA and TT of rhubarb (at 5.40 g crude drugs/kg and 14.69 g crude drugs/kg) were intragastrically administrated to rats in all groups except the blank group and the model group, once daily for 6 successive days.The general state of rats, biochemical indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), laminin (LN), hyaluronic acid (HA), transforming growth factor beta1 (TGF-beta1), as well pathological results of rat liver tissues. Finally the protection laws of TA and TT for rats' liver were analyzed using factor analysis.. Compared with the blank control group, all biochemical indices increased in the blank group (P < 0.05, P < 0.01). HA also increased in the blank + high dose TA group; AST, ALT, and HA also increased in the blank +high dose TT group (P < 0.05). Compared with the model group, AST, ALT, ALP, HA, and TGF-beta1 significantly decreased in the model + low dose TA group, the model + high dose TA group, the model + low dose TT group (P < 0.05, P < 0.01). Serum AST, ALT, and ALP also decreased in the model + high dose TT group (P < 0.05, P < 0.01). Pathological results showed that mild swollen liver cells in the model + high dose TA group. Fatty degeneration and fragmental necrosis around the central veins occurred in the blank + high dose TA group. The pathological injury was inproved in the model +low dose TA group. Two common factors, liver fibrosis and liver cell injury, were extracted by using factor analysis. TA showed stronger improvement of the two common factors than TT.. Rhubarb TA and TT showed protective and harmful effects on rats' liver. At an equivalent dosage, TA had better liver protection than TT. High dose TT played a role in liver injury to some extent.

Topics: Animals; Anthraquinones; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Female; Liver; Male; Rats; Rats, Sprague-Dawley; Rheum; Tannins

To evaluate antioxidant, anti-inflammatory, hepatoprotective and vasorelaxant activities of Populus nigra flower buds ethanolic extract.. Antioxidant and anti-inflammatory activities of the extract were assessed using respectively the ABTS test and the animal model of carrageenan-induced paw edema. Protection from hepatic toxicity caused by aluminum was examined by histopathologic analysis of liver sections. Vasorelaxant effect was estimated in endothelium-intact and -rubbed rings of porcine coronary arteries precontracted with high concentration of U46619.. The results showed a moderate antioxidant activity (40%), but potent anti-inflammatory activity (49.9%) on carrageenan-induced mice paw edema, and also as revealed by histopathologic examination, complete protection against AlCl₃-induced hepatic toxicity. Relaxant effects of the same extract on vascular preparation from porcine aorta precontracted with high concentration of U46619 were considerable at 10⁻¹ g/L, and comparable (P>0.05) between endothelium-intact (67.74%, IC₅₀=0.04 mg/mL) and -rubbed (72.72%, IC₅₀=0.075 mg/mL) aortic rings.. The extract exerted significant anti-inflammatory, hepatoprotective and vasorelaxant activities, the latter being endothelium-independent believed to be mediated mainly by the ability of components present in the extract to exert antioxidant properties, probably related to an inhibition of Ca²⁺ influx.

Topics: Aluminum Chloride; Aluminum Compounds; Analysis of Variance; Animals; Anti-Inflammatory Agents; Cardiovascular Agents; Carrageenan; Chemical and Drug Induced Liver Injury; Chlorides; Edema; Female; Flavonoids; Flowers; Liver; Male; Mice; Nitric Oxide; Nitric Oxide Synthase Type III; Phenols; Plant Extracts; Populus; Protective Agents; Tannins

Medicinal plants constitute a principal health care resource corroborating their gradual acceptance by the global population. The ethno medicinal plant, Murraya koeniggi (Curry-leaf tree) as is native to India exhibits diverse biological activities. Unpublished data from our laboratory revealed hepatoprotective activity of its crude aqueous extract against ethanol-induced hepatotoxicity in experimental animals. Chronic ethanol consumption diminishes the cellular antioxidant levels through free radical induced injury causing hepatitis and cirrhosis with mortality in severe cases. This provided a rationale for studying its mechanistic approaches in terms of modulation of antioxidant defenses for probable hepatoprotective activity against ethanol-induced hepatotoxicity in vitro. Based on the inhibitory concentration (IC(50)) obtained from the cell viability assay, graded concentrations of 100 μg/ml and 500 μg/ml of aqueous extract (WE), isolated carbazole alkaloids (CA) and tannin (T) fraction were chosen to study the hepatoprotective activity against ethanol-induced hepatotoxicity using liver carcinoma cell lines (Hep G(2)). Their antioxidant activity with anti-lipid peroxidation potential (LPO), effects on protein content, liver metabolizing enzymes viz., glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and the morphology of the cells were studied as parameters of hepatoprotection. The tannins and the carbazole alkaloids from the aqueous extract exhibited excellent hepatoprotective activity with respect to the different parameters studied and maintained normal morphology even after ethanolic challenge to the cells as comparable to the protection offered by the standard drug L-ornithine L-aspartate (LOLA). The modulating effect of the aqueous extract and isolates on liver metabolizing enzymes, reduction in lipid peroxidation and decreased cellular damage were found to contribute to the hepatoprotective activity.

Topics: Alkaloids; Antioxidants; Biphenyl Compounds; Carbazoles; Catalase; Cell Survival; Chemical and Drug Induced Liver Injury; Ethanol; Free Radicals; Glutathione; Hep G2 Cells; Humans; Lipid Peroxidation; Models, Biological; Murraya; Picrates; Plant Extracts; Plant Leaves; Superoxide Dismutase; Tannins

Drug-induced liver injury is one of the main causes of drug attrition. The ability to predict the liver effects of drug candidates from their chemical structures is critical to help guide experimental drug discovery projects toward safer medicines. In this study, we have compiled a data set of 951 compounds reported to produce a wide range of effects in the liver in different species, comprising humans, rodents, and nonrodents. The liver effects for this data set were obtained as assertional metadata, generated from MEDLINE abstracts using a unique combination of lexical and linguistic methods and ontological rules. We have analyzed this data set using conventional cheminformatics approaches and addressed several questions pertaining to cross-species concordance of liver effects, chemical determinants of liver effects in humans, and the prediction of whether a given compound is likely to cause a liver effect in humans. We found that the concordance of liver effects was relatively low (ca. 39-44%) between different species, raising the possibility that species specificity could depend on specific features of chemical structure. Compounds were clustered by their chemical similarity, and similar compounds were examined for the expected similarity of their species-dependent liver effect profiles. In most cases, similar profiles were observed for members of the same cluster, but some compounds appeared as outliers. The outliers were the subject of focused assertion regeneration from MEDLINE as well as other data sources. In some cases, additional biological assertions were identified, which were in line with expectations based on compounds' chemical similarities. The assertions were further converted to binary annotations of underlying chemicals (i.e., liver effect vs no liver effect), and binary quantitative structure-activity relationship (QSAR) models were generated to predict whether a compound would be expected to produce liver effects in humans. Despite the apparent heterogeneity of data, models have shown good predictive power assessed by external 5-fold cross-validation procedures. The external predictive power of binary QSAR models was further confirmed by their application to compounds that were retrieved or studied after the model was developed. To the best of our knowledge, this is the first study for chemical toxicity prediction that applied QSAR modeling and other cheminformatics techniques to observational data generated by the means of automate

Topics: Animals; Chemical and Drug Induced Liver Injury; Cluster Analysis; Databases, Factual; Humans; MEDLINE; Mice; Models, Chemical; Molecular Conformation; Quantitative Structure-Activity Relationship

The protective effect of green tea (Camellia sinensis) was tested against arsenic-induced toxicity. However, the possible role of tannins in green tea in alleviating hepatic and renal oxidative injury has also been studied. Administration of sodium arsenite (100 mg/kg/day) for 28 days in Sprague Dawley female rats resulted in significant reduction of biochemical parameters such as delta-aminolevulinic acid dehydratase (ALAD), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and elevation of thiobarbituric acid reactive substances (TBARS) and the index of nitrite/nitrate (NOx) levels. The tissue arsenic burden was increased after arsenic exposure for a period of 28 days. Green tea crude fraction (GTC) co-treated with sodium arsenite for 28 days caused significant (p < .01) elevation of ALAD, GSH, GPx, SOD, and nitrate/nitrite levels and reduction of the TBARS level and tissue burden when compared to detannified green tea fraction (GTDT)-treated groups. The protective role of tannin-rich fraction of C. sinensis when compared to the detannified fraction was also confirmed by histological examinations. The greater activity of GTC than that of detannified green tea fraction correlates with the higher content of tannins in green tea. Overall, these results indicate that the tannin-rich green tea could have improved the defense mechanism against arsenic-induced oxidative stress and reduced the tissue arsenic burden.

Topics: Animals; Arsenic; Arsenic Poisoning; Arsenites; Biomarkers; Camellia sinensis; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Female; Kidney; Liver; Oxidative Stress; Phytotherapy; Plant Extracts; Plant Leaves; Porphobilinogen Synthase; Protective Agents; Random Allocation; Rats; Rats, Sprague-Dawley; Renal Insufficiency; Sodium Compounds; Tannins

Azidothymidine (AZT) is known to decrease HIV virus replication and is one of the most frequently prescribed antiretroviral drugs used for AIDS treatment. Dose-limiting toxicities are the major curse associated with AZT therapy. Recently, we have reported that tannic acid; a PARG inhibitor prevents cisplatin induced nephrotoxicity. The present work was conceived to study the effect of tannic acid on AZT induced hepatotoxicity and genotoxicity. AZT induces increase in plasma levels of ALT, AST and alkaline phosphatase along with increase in micronucleus (MN) count in peripheral blood. Suggesting, AZT is hepatotoxic and genotoxic to mice. Treatment of tannic acid protects AZT induced hepatotoxicity by decreasing the ALT, AST and alkaline phosphatase levels. It also significantly reduces the oxidative damage by preventing reduction in glutathione and decreasing the level of malondialdehyde in liver of AZT treated mice. In addition, tannic acid decreases the PARG expression, PARP cleavage and histone H3 acetylation in liver of AZT treated mice. Moreover, treatment of tannic acid also decreases MN count in peripheral blood, suggesting its anti-mutagenic effect. In light of these findings we suggest the potential role of tannic acid treatment in preventing AZT induced toxicity.

Topics: Acetylation; Alanine Transaminase; Alkaline Phosphatase; Animals; Anti-HIV Agents; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; DNA Damage; Glycoside Hydrolases; Histones; Liver; Liver Diseases; Malondialdehyde; Mice; Micronucleus Tests; Oxidative Stress; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Tannins; Zidovudine

The polyphenol-rich fraction (WP, 45% polyphenol) prepared from the kernel pellicles of walnuts was assessed for its hepatoprotective effect in mice. A single oral administration of WP (200 mg/kg) significantly suppressed serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) elevation in liver injury induced by carbon tetrachloride (CCl 4), while it did not suppress d-galactosamine (GalN)-induced liver injury. In order to identify the active principles in WP, we examined individual constituents for the protective effect on cell damage induced by CCl 4 and d-GalN in primary cultured rat hepatocytes. WP was effective against both CCl 4- and d-GalN-induced hepatocyte damages. Among the constituents, only ellagitannins with a galloylated glucopyranose core, such as tellimagrandins I, II, and rugosin C, suppressed CCl 4-induced hepatocyte damage significantly. Most of the ellagitannins including tellimagrandin I and 2,3- O-hexahydroxydiphenoylglucose exhibited remarkable inhibitory effect against d-GalN-induced damage. Telliamgrandin I especially completely suppressed both CCl 4- and d-GalN-induced cell damage, and thus is likely the principal constituent for the hepatoprotective effect of WP.

Topics: Animals; Carbon Tetrachloride; Cells, Cultured; Chemical and Drug Induced Liver Injury; Flavonoids; Galactosamine; Gallic Acid; Glucosides; Hydrolysis; Juglans; Liver Diseases; Phenols; Polyphenols; Rats; Seeds; Tannins

The antioxidant and hepatoprotective actions of Terminalia catappa L. collected from Okinawa Island were evaluated in vitro and in vivo using leaves extract and isolated antioxidants. A water extract of the leaves of T. catappa showed a strong radical scavenging action for 1,1-diphenyl-2-picrylhydrazyl and superoxide (O(2)(.-)) anion. Chebulagic acid and corilagin were isolated as the active components from T. catappa. Both antioxidants showed a strong scavenging action for O(2)(.-) and peroxyl radicals and also inhibited reactive oxygen species production from leukocytes stimulated by phorbol-12-myristate acetate. Galactosamine (GalN, 600 mg/kg, s.c.,) and lipopolysaccharide (LPS, 0.5 microg/kg, i.p.)-induced hepatotoxicity of rats as seen by an elevation of serum alanine aminotransferase, aspartate aminotransferase and glutathione S-transferase (GST) activities was significantly reduced when the herb extract or corilagin was given intraperitoneally to rats prior to GalN/LPS treatment. Increase of free radical formation and lipid peroxidation in mitochondria caused by GalN/LPS treatment were also decreased by pretreatment with the herb/corilagin. In addition, apoptotic events such as DNA fragmentation and the increase in caspase-3 activity in the liver observed with GalN/LPS treatment were prevented by the pretreatment with the herb/corilagin. These results show that the extract of T. catappa and its antioxidant, corilagin are protective against GalN/LPS-induced liver injury through suppression of oxidative stress and apoptosis.

Topics: Animals; Antioxidants; Chemical and Drug Induced Liver Injury; Free Radicals; Galactosamine; Glucosides; Hydrolyzable Tannins; Lipopolysaccharides; Liver; Male; Phytotherapy; Plant Extracts; Plant Leaves; Protective Agents; Rats; Rats, Sprague-Dawley; Tannins; Terminalia

Punicalagin and punicalin were isolated from the leaves of Terminalia catappa L., a Combretaceous plant distributed throughout tropical and subtropical beaches, which is used for the treatment of dermatitis and hepatitis. Our previous studies showed that both of these compounds exert antioxidative activity. In this study, the antihepatotoxic activity of punicalagin and punicalin on acetaminophen-induced toxicity in the rat liver was evaluated. After evaluating the changes of several biochemical functions in serum, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were increased by acetaminophen administration and reduced by punicalagin and punicalin. Histological changes around the hepatic central vein and oxidative damage induced by acetaminophen were also recovered by both compounds. The data show that both punicalagin and punicalin exert antihepatotoxic activity, but treatment with larger doses enhanced liver damage. These results suggest that even if punicalagin and punicalin have antioxidant activity at small doses, treatment with larger doses will possibly induce some cell toxicities.

Topics: Acetaminophen; Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Hydrolyzable Tannins; Lipid Peroxidation; Liver; Liver Diseases; Male; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Rosales; Tannins

A study was conducted to identify and characterise the toxic principle in Terminalia oblongata, commonly known as yellow-wood. Crude aqueous extracts of yellow-wood leaf were found to produce the same liver lesion in mice as has been reported in ruminants. The hepatotoxic fraction was isolated and identified as a hydrolysable vegetable tannin called punicalagin. When given orally, the dose required to produce toxicity was at least 20 times greater than when given intraperitoneally. Following a given dose of punicalagin, the onset and severity of liver necrosis was found to be related to the time interval after dosing. In addition to punicalagin, an unidentified nephrotoxic substance was found which was capable of producing avascular renal necrosis without liver necrosis.

Topics: Administration, Oral; Animals; Chemical and Drug Induced Liver Injury; Injections, Intraperitoneal; Kidney Diseases; Liver Diseases; Male; Mice; Microscopy, Electron; Necrosis; Plants, Toxic; Tannins

The antihepatotoxic effects of tannin analogues were examined utilizing carbon tetrachloride- and galactosamine-induced cytotoxicity in primary cultured rat hepatocytes. Most tannins showed significant antihepatotoxic effects in these two assay systems. Hydrolyzable tannins generally exhibited an intense enzyme inhibitory action on glutamic-pyruvic transaminase while condensed tannins exerted a much less inhibitory action, although variations were observed depending on structure. Structure-activity relationships are discussed.

Topics: Alanine Transaminase; Animals; Carbon Tetrachloride Poisoning; Cells, Cultured; Chemical and Drug Induced Liver Injury; Galactosamine; Rats; Tannins

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Glucosides; Glycosides; Hydrolyzable Tannins; Lipid Peroxides; Male; Oils; Plant Extracts; Rats; Rats, Inbred Strains; Tannins; Zea mays

The effect of intraperitoneal administration of an aqueous solution of tannic acid was examined after different intervals of time. The results showed a gradual and progressive destruction of the liver cells and transformation of its architecture. The histological signs of liver damage appeared 2 hrs after the intoxication. Mild necrosis at periphery was noted even after 1 hour. After 2 hrs hepatocytes were swollen and sinusoids were contracted. These changes became more pronounced after 12 hrs and by 24 hrs extensive centrolobular and perilobular necroses and severe hydropic degeneration of liver cells were observed. Nuclear volume increased at the very first stage of necrosis but after 48 hrs binucleate and multinucleate cells were also visible. The nucleolus was hypertropied and divided into two or more portions after 1 hour. Connective tissue was degnerated after 24 hrs. Hepatic fibrosis was observed after five days of treatment. In all the present experiments vascular lesions and bile duct hyperplasia were the common phenomena.

Topics: Animals; Chemical and Drug Induced Liver Injury; Fishes; Hydrolyzable Tannins; Liver; Necrosis; Tannins; Time Factors

Topics: Adolescent; Adult; Aged; Alkaline Phosphatase; Barium Sulfate; Chemical and Drug Induced Liver Injury; Child; Digestive System; Female; Humans; Liver; Liver Function Tests; Male; Middle Aged; Radiography; Tannins; Time Factors; Transaminases

Topics: Animals; Bile; Chemical and Drug Induced Liver Injury; Intubation, Gastrointestinal; Liver; Liver Function Tests; Liver Regeneration; Male; Mononuclear Phagocyte System; Organ Size; Phagocytosis; Rats; Sulfobromophthalein; Tannins; Triglycerides

Topics: Acetamides; Animals; Antigens; Beryllium; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Common Bile Duct; Female; Fluorescent Antibody Technique; Goats; Immune Sera; Immunodiffusion; Liver Diseases; Male; Organ Specificity; Proteinuria; Rabbits; Rats; Tannins; Urethane

Topics: Acute Disease; Adolescent; Adult; Aged; Anticonvulsants; Antitubercular Agents; Azathioprine; Blood Transfusion; Chemical and Drug Induced Liver Injury; Child; Female; Halothane; Hepatic Encephalopathy; Hepatitis A; Hepatitis B; Humans; Infant; Leukocytosis; Liver Diseases; Male; Middle Aged; Necrosis; Penicillins; Prothrombin Time; Sulfonamides; Tannins

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; Barium Sulfate; Chemical and Drug Induced Liver Injury; Contrast Media; Female; Gallic Acid; Injections, Subcutaneous; Liver Function Tests; Male; Rabbits; Rats; Tannins

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: Burns; Chemical and Drug Induced Liver Injury; Humans; Tannins

Topics: Animals; Cathartics; Chemical and Drug Induced Liver Injury; Colon; Colonic Diseases; Edema; Enema; Intestinal Mucosa; Liver; Rats; Tannins

Topics: Animals; Blood; Cathartics; Chemical and Drug Induced Liver Injury; Colon; Enema; Gallic Acid; Injections, Intraperitoneal; Intestinal Absorption; Rats; Tannins

Topics: Barium Sulfate; Chemical and Drug Induced Liver Injury; Digestive System; Enema; Humans; Liver Function Tests; Radiography; Tannins

Topics: Barium Sulfate; Chemical and Drug Induced Liver Injury; Colon; Humans; Radiography; Tannins

Topics: Barium; Chemical and Drug Induced Liver Injury; Colonic Diseases; Enema; Humans; Intestinal Absorption; Radiography; Tannins

Topics: Chemical and Drug Induced Liver Injury; Fatty Liver; Hepatitis; Liver Diseases; Liver Glycogen; Necrosis; Pathology; Rabbits; Research; Tannins; Toxicology

The LD(50) +/- S.E. of tannic acid given orally to albino rats was found to be 2.26+/-0.083 g. per kg. body weight, which is higher than its apparent LD(50) when given per rectum. The immediate cause of death was respiratory failure preceded by convulsions when death occurred early and by hypothermic cachexia when death was delayed. Death was associated with a progressively developing hepatic necrosis and nephritis and a temporary acute gastroenteritis. It was accompanied by loss of weight and edema in many organs, evidence of stimulation of the spleen, adrenal cortex and testes, and atrophy of the thymus. Recovery in survivors was associated with a temporary increase in weight of the spleen and testes and persistence of loss of weight in the adrenal, pyloric stomach, and skin.

Topics: Cachexia; Chemical and Drug Induced Liver Injury; Edema; Gastroenteritis; Hepatitis; Hepatitis A; Hypothermia; Liver Diseases; Nephritis; Pathology; Rats; Research; Seizures; Spleen; Tannins; Toxicology

Topics: Aspartate Aminotransferases; Barium Sulfate; Chemical and Drug Induced Liver Injury; Coronary Disease; Crohn Disease; Diabetes Mellitus; Enema; Enteritis; Geriatrics; Hepatitis; Humans; Pharmacology; Research; Tannins; Transaminases

Topics: Amides; Chemical and Drug Induced Liver Injury; Chloroform; Complement Fixation Tests; Hepatitis; Nitrosamines; Paraffin; Rats; Research; Sulfhydryl Compounds; Tannins; Toxicology

Topics: Barium; Barium Sulfate; Chemical and Drug Induced Liver Injury; Enema; Hepatitis; Humans; Radiography; Radiography, Abdominal; Tannins; Toxicology; Viral Vaccines

Topics: Barium Sulfate; Chemical and Drug Induced Liver Injury; Child; Enema; Geriatrics; Hepatitis; Hepatitis A; Humans; Liver Cirrhosis; Radiology; Tannins; Toxicology

Tannic acid contained in the barium enema was found to have been the sole known potential hepatotoxin in four of the five cases of fulminating fatal liver failure that occurred in a 213-bed hospital over a period of 27 months. In the other case halothane anesthesia had also been administered. Autopsies (performed on four of the cases) did not suggest viral hepatitis but showed substantially indentical hepatic changes, not unlike those reported in the past following tannic acid exposure. Proof is not claimed that tannic acid was the cause of these deaths, but further investigation regarding the safety of its administration in barium enemas is advocated.

Topics: Barium; Barium Sulfate; Chemical and Drug Induced Liver Injury; Enema; Hepatitis; Hepatitis A; Humans; Liver Diseases; Radiography, Abdominal; Tannins; Toxicology