Activation of Autophagy Relieves Linoleic Acid-Induced Inflammation in Large Yellow Croaker (Larimichthys crocea).

High levels of soybean oil (SO) in fish diets enriched with linoleic acid (LA, 18:2n-6) could induce strong inflammation. However, the molecular mechanism underlying LA-induced inflammation in the liver of large yellow croaker (Larimichthys crocea) has not been elucidated. Based on previous research, autophagy has been considered a new pathway to relieve inflammation. Therefore, the present study was performed to investigate the role of autophagy in regulating LA-induced inflammation in the liver of large yellow croaker in vivo and in vitro. The results of the present study showed that activation of autophagy in liver or hepatocytes could significantly reduce the gene expression of proinflammatory factors, such as tumor necrosis factor α (TNFα) and interleukin 1ß (IL1ß). The results of the present study also showed that inhibition of autophagy could upregulate the gene expression of proinflammatory factors and downregulate the gene expression of anti-inflammatory factors in vivo and in vitro. Furthermore, autophagy could alleviate LA-induced inflammatory cytokine gene expression in vivo and in vitro, while inhibition of autophagy obtained the opposite results. In conclusion, our study shows that autophagy could regulate inflammation and alleviate LA-induced inflammation in the liver of large yellow croaker in vivo and in vitro for the first time, which may offer considerable benefits to the aquaculture industry and human health.

Extracts of Qizhu decoction inhibit hepatitis and hepatocellular carcinoma in vitro and in C57BL/6 mice by suppressing NF-κB signaling.

Hepatitis and hepatocellular carcinoma are serious human diseases. Here, we examined the in vivo and in vitro inhibitory effect of extracts of Qizhu decoction (a traditional Chinese medicine) on hepatitis caused by diethylnitrosamine or hepatitis B virus and on diethylnitrosamine-induced hepatocellular carcinoma. The results showed that both the aqueous and ethanol extracts (QC and QS, respectively) of Qizhu decoction significantly inhibited hepatic inflammation and liver cancer induced by diethylnitrosamine or hepatitis B virus by suppressing NF-κB signaling and decreasing the levels of TNF-α and IL-1ß. Both QC and QS inhibited the proliferation and migration of primary cancer hepatocytes by reducing cyclin B1, cyclin D1 and N-cadherin expression and increasing E-cadherin expression. QC and QS also promoted the apoptosis of primary cancer hepatocytes by upregulating caspase-3 and downregulating BCL-2 expression. The knockdown of p65 in NF-κB signaling inhibited the ability of QC and QS to significantly reduce the colony formation ability of liver cancer cells. Additionally, QC and QS might significantly inhibit the DNA replication of hepatitis B virus in vivo and in vitro, and we found that corilagin and polydatin were the active compounds of QC and QS. Taken together, our in vitro findings and our results in C57BL/6 mice showed that extracts of Qizhu decoction might inhibit hepatitis and hepatocellular carcinoma by suppressing NF-κB signaling.

Fenugreek seed powder mitigates cadmium-induced testicular damage and hepatotoxicity in male rats.

Cadmium is a potential environmental and industrial pollutant affecting human tissues and organs including liver and testes. The protective role of fenugreek seed powder (FSP) was investigated in male rats subjected to cadmium-induced testicular injury and hepatic dysfunction. Testicular damage and hepatotoxicity were induced by oral administration of cadmium chloride (5 mg/kg body weight, once a day) for 7 weeks. FSP was given at 5% w/w in chow diet for 8 weeks, starting 1 week before cadmium administration. FSP intake significantly increased serum testosterone level and testis weight that were reduced by cadmium. FSP also compensated deficits in hepatic and testicular antioxidant defense system, interleukin-4 and nitric oxide levels, reduced serum liver function enzyme activities and suppressed lipid peroxidation in hepatic and testicular tissues resulted from cadmium administration. Additionally, FSP attenuated the cadmium-induced elevations in hepatic and testicular tumor necrosis factor-α and transforming growth factor-beta1 levels as well as cadmium deposition and hydroxyproline content. The protective effect afforded by FSP was mainly due its antioxidant, antifibrotic and anti-inflammatory effects. In conclusion, the results of the present work indicated that FSP may represent a promising medicinal herb to protect hepatic and testicular tissues from the detrimental effects of cadmium.

[Hepatoprotective effect of thiophane in rats with experimental carbon tetrachloride-induced hepatitis].

A hepatoprotective effect of thiophan was studied on the model of carbon tetrachloride-induced hepatitis in rats. Therapeutic administration of thiophan repairs the antitoxic function of liver, normalizes cytolysis marker activity, and improves the synthetic function of liver and the carbohydrate and lipid metabolism. The hepatoprotective activity of thiophan is similar to effect of silimarin.

Dietary management of hepatic copper accumulation in Labrador Retrievers.

BACKGROUND: Copper-associated chronic hepatitis (CACH) recently has been recognized in the Labrador Retriever as an inherited disorder with a late onset of clinical signs. No studies have investigated dietary management for the long-term treatment of this disease or for its potential in delaying the onset of clinical signs in subclinical cases. OBJECTIVES: To investigate the effects of a low-copper diet and zinc gluconate on hepatic copper concentrations in Labrador Retrievers with abnormal hepatic copper concentrations. ANIMALS: Twenty-four client-owned Labradors that were related to patients affected with CACH and that had been diagnosed with increased hepatic copper concentrations. METHODS: Hepatic copper concentrations were assessed before and after an average of 8 and 16 months of treatment. During this time, all dogs were fed exclusively a low-copper diet. In addition, dogs were assigned to 1 of 2 groups in a randomized double-blind manner to receive a supplement of zinc gluconate or placebo. RESULTS: Twenty-one dogs completed the study. Hepatic copper concentrations decreased in both groups at recheck 1 (n = 21; group 1, P < .001; group 2, P= .001) and at recheck 2 (n= 16; group 1, P= .03; group 2, P= .04). No difference in hepatic copper concentrations was found between the 2 groups before treatment (P= .65), at recheck 1 or at recheck 2 (P= .52-.79). CONCLUSIONS AND CLINICAL RELEVANCE: Feeding low-copper diets to Labradors is effective in decreasing hepatic copper concentrations. Adjunctive treatment with zinc does not appear to increase the copper-lowering effects of dietary management.

[Effect of phytopreparation Narcophyt on choleretic reaction in white rats with experimental hepatitis].

Experiments on white rats show that the phytopreparation Narcophyt possesses choleretic activity. In rats with experimental hepatitis induced by ethanol, the course of therapeutic and prophylactic administration of Narcophyt favorably influenced the bile secreting function of the liver, accelerated bile secretion, stimulated the synthesis and secretion of cholates, as well as the secretion of bilirubin and excretion of cholesterol. The cholagogic effect of Narcophyt was comparable with that of the reference drug cholosas.

Tetrandrine protects mice from concanavalin A-induced hepatitis through inhibiting NF-kappaB activation.

Tetrandrine (TET) is the major pharmacologically active compound of Chinese herb Stephania tetrandra S Moore, which has been used traditionally for the treatment of rheumatic disorders, silicosis and hypertension. Concanavalin A (ConA)-induced hepatitis (CIH) is a T-cell-dependent hepatitis and a well-established animal model for studying the mechanisms and therapy of immune-mediated hepatotoxicity. The aim of this study was to investigate whether TET could protect mice from CIH. C57BL/6 mice were injected with ConA to induce CIH pretreated with or without TET. Liver injury was assessed biochemically and histologically. Levels of plasma cytokines and the expressions of chemokine messenger RNA (mRNA) in the liver were determined. We found that pretreatment of mice with TET markedly reduced plasma transaminase release and the severity of liver damage. We further investigated the mechanisms of the protective effects of TET. When CIH-induced mice pretreated with TET, the increases of plasma concentrations of TNF-alpha, IFN-gamma, IL-12 and IL-4 were dramatically attenuated; at the same time, IFN-inducible protein-10 and macrophage inflammatory protein-1alpha expressions in liver were decreased. Furthermore, TET inhibited NF-kappaB activity, the critical transcriptional factor of the above mentioned inflammatory cytokines, by preventing the activation of IkappaBalpha kinasealpha (IKKalpha) and then inhibiting phosphorylation of IkappaBalpha to stabilize IkappaBalpha in intrahepatic leukocytes. In conclusion, TET is able to prevent T-cell-mediated liver injury in vivo. The beneficial effect may depend on suppressing the production of various inflammatory mediators in the liver through inhibiting of NF-kappaB activation.

[Hepatoprotective effect of Gossipium hirsutum extract on acute experimental hepatitis on rat liver injury].

OBJECTIVE: To investigate the protective effect on the mice acute experimental hepatic injury by Flos Gossypium herbaceum extracts (FGF-I, FGF-II). METHOD: Experimental hepatic injury model was established by a single intraperitoneal injection of 350 mg x kg(-1) D-CalN in Wistar rats. Serum samples for alanine aminotransferase (ALT), aspartate transferase (AST) level and liver homogenate samples for super oxide dismutase (SOD), malondialdehyde (MDA), Glutathione peroxidese (GSH-PX) activities were assayed. RESULT: For acute experimental hepatic injury, FGF-I and FGF-II significantly decrease the serum transaminase activities (P < 0.01). FGF-I increased the SOD activities (P < 0.01), and decreased MDA content only for 50 mg x kg(-1) FGF-I (P < 0.05), no effect on GSH-PX activity was found for them. FGF-II increased the SOD and GSH-PX activity (P < 0.05) with decreased MDA content (P < 0.05). CONCLUSION: FGF-I and FGF-II showed significant protective action in mice experimental hepatic injury.

Sodium tanshinone IIA sulfonate protects mice from ConA-induced hepatitis via inhibiting NF-kappaB and IFN-gamma/STAT1 pathways.

INTRODUCTION: Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, the main pharmacologically active component of Salvia miltiorrhiza. The aim of this study was to investigate the effect of STS on concanavalin A (ConA)-induced hepatitis (CIH) in mice, an experimental model of immune-mediated liver injury. RESULTS: C57BL/6 mice pretreated with STS released much less alanine transaminase into plasma in response to ConA challenge and had reduced inflammatory infiltration and hepatocyte apoptosis in the liver compared with control mice pretreated with vehicle solutions. Thus, STS protected mice from CIH. In STS-pretreated mice induced with CIH, we found abrogated tumor necrosis factor-alpha and interferon (IFN)-gamma production. Moreover, mRNA expressions of IFN-inducible protein-10 and macrophage inflammatory protein-1alpha in these mice were decreased. The mechanism of anti-inflammatory effects of STS may be attributed to its modulation of crucial inflammatory signaling pathways, including NF-kappaB and IFN-gamma/STAT1. CONCLUSION: In conclusion, STS was capable of protecting mice from immune-mediated liver injury in vivo, and the protection was associated with its suppressive effect on the production of important inflammatory mediators through modulating NF-kappaB and IFN-gamma/STAT1 signaling pathways.

Further studies on the hepatoprotective effects of Anoectochilus formosanus.

The purpose of this study was to investigate the hepatoprotective effects of Anoectochilus formosanus effective fraction (AFEF) on chronic liver damage induced by carbon tetrachloride (CCl4) in mice. CCl4 (5%; 0.1 mL/10 g body weight) was given twice a week for 9 weeks, and mice received AFEF throughout the whole experimental period. Plasma GPT, hepatic levels of hydroxyproline and malondialdehyde were significantly lower in mice treated with AFEF compared with those treated with CCl4 only. Liver pathology in the AFEF-treated mice was also improved. RT-PCR analysis showed that AFEF treatment increased the expression of methionine adenosyltransferase 1A and decreased the expression of collagen(alpha1)(I) and transforming growth factor-beta1. These results clearly demonstrated that AFEF reduced the hepatic damage induced by CCl4 in mice.

Anti-hepatitis B activities of ganoderic acid from Ganoderma lucidum.

Ganoderic acid, from Ganoderma lucidum, at 8 microg/ml inhibited replication of hepatitis B virus (HBV) in HepG2215 cells over 8 days. Production of HBV surface antigen and HBV e antigen were 20 and 44% of controls without ganoderic acid. Male KM mice were significantly protected from liver injury, induced with carbon tetrachloride, by treatment with ganoderic acid at 10 mg and 30 mg/kg x d (by intravenous injection) 7 days. Ganoderic acid at the same dosage also significantly protected the mice from liver injury induced by M. bovis BCG plus lipopolysaccharide (from Escherichia coli 0127:B8).

Melatonin-selenium nanoparticles protects liver against immunological injury induced by bacillus Calmette-Guerin and lipopolysaccharide.

AIM: Melatonin-selenium nanoparticle (MT-Se), a novel complex, was synthesized by preparing selenium nanoparticles in a melatonin medium. The present investigation was designed to determine the protective effects of MT-Se against immunological liver injury in mice induced by bacillus Calmette-Guerin (BCG)/lipopolysaccharide (LPS). METHODS: The model of immunological liver injury in mice was prepared. The levels of alanine aminotransferase, aspartate amino-transferase, nitric oxide (NO) in serum, malondialdehyde content, superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) activities in a liver homogenate were assayed by spectrophotometry. The content of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) were determined by ELISA. The splenocyte proliferation was assayed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) dye reduction. Meanwhile, a hepatic pathological examination was observed. RESULTS: In the BCG/LPS-induced hepatic injury model, MT-Se administered at doses of 5, 10, or 20 mg/kg to the BCG/LPS-treated mice for 10 d significantly reduced the increase in serum aminotransferase, reduced the severe extent of hepatic cell damage and the immigration of inflammatory cells. It also attenuated the increase in the content of thiobarbituric acid-reactive substances and enhanced the decrease in activities of SOD and GSH-px. In contrast, the treatment with MT-Se suppressed the increase in NO level in both the serum and liver tissue. Furthermore, MT-Se significantly lowered an increase in TNF-alpha and IL-1beta levels in the liver and inhibited the production of TNF- alpha and IL-1beta by peritoneal macrophages. A downregulation effect of MT-Se on splenocyte proliferation was also observed. CONCLUSION: MT-Se showed a hepatic protective action on immunological liver injury in mice.

Effects of CH-100, a chinese herbal medicine, on acute concanavalin A-mediated hepatitis in control and alcohol-fed rats.

BACKGROUND: Administration of concanavalin A (Con A) leads to acute hepatitis that involves T-cell activation and inflammatory mediator production in mice and rats. We examined the role of CH-100, a Chinese herbal medicine previously trialed in human hepatitis C, in the prevention of Con A-related, T-cell-mediated, acute liver injury in rats. METHODS: Female Wistar rats were fed 40% ethanol, 2% sucrose, or isocaloric sucrose for 8 weeks. At the same time, these animals were fed either the Chinese herbal medicine CH-100 (4 tablets/kg body weight/ day) or placebo in chow daily. Blood from the tail vein was collected for endotoxin (lipopolysaccharide) assay at 0, 4, and 8 weeks of ethanol consumption. Twenty-four hours after injection of Con A (20 mg/kg body weight) or phosphate-buffered saline, blood from the tail vein was collected for alanine aminotransferase and tumor necrosis factor (TNF)-alpha assays. Liver-associated CD4+ T cells were isolated from liver perfusates and then cultured with Con A (5 microg/ml) at 37 degrees C for 24 hr. Supernatants were harvested for TNF-alpha assay. The proportion of CD4+ T cells in blood and liver perfusates was measured. Liver samples were collected for histopathological analysis. RESULTS: Lipopolysaccharide levels were significantly reduced in CH-100-treated ethanol-fed rats compared with placebo-treated rats. After Con A injection, alanine aminotransferase levels were lower at 12 and 24 hr in herb-treated rats compared with placebo-treated rats. Furthermore, serum TNF-alpha levels were lower in ethanol-fed rats on herbal treatment. A significant decrease in TNF-alpha production by liver-associated CD4+ T cells in culture was observed in CH-100-treated ethanol-fed rats. CH-100 treatment was associated with a decreased percentage of CD4+ cells in both blood and liver perfusate in all groups. Herb-treated rats displayed markedly less hepatic necrosis and a reduced CD4+ T-cell infiltrate in portal areas than did placebo-fed rats. CONCLUSIONS: The results demonstrate that CH-100 modified the T-cell response to Con A injection. The effect was more marked in ethanol-fed rats, which suggests a possible role for CH-100 in treating alcoholic liver disease.

Suppression of chemically and immunologically induced hepatic injuries by gentiopicroside in mice.

Gentiopicroside (GPS), a main bitter secoiridoid constituent of roots of Gentiana macrophylla Pall., was tested for therapeutic effects on the two hepatic injury models, the CCl4-induced and lipopolysaccharide (LPS)/bacillus Calmette-Guerin (BCG)-induced hepatitides. An increase in serum level of hepatic aminotransferases (GOT: EC 2.6.1.1. and GPT: EC 2.6.1.2.) induced by a p.o. treatment of CCl4 was suppressed by pretreatment with GPS at 30-60 mg/kg/day for 5 consecutive days. An increase of these enzymes triggered by an i.v. treatment with LPS in mice primed with bacillus Calmette-Guerin (BCG) was also inhibited by GPS pretreatment at the same dose of GPS. In the BCG/LPS model, tumor necrosis factor (TNF), a major inflammatory mediator, was increased in serum with a peak at 90-120 min, followed by an increase of serum transaminase activities. GPS treatment significantly suppressed the increase of TNF in serum at the therapeutic doses, suggesting that GPS protected against hepatitis by inhibiting the production of TNF.

Anti-hepatitic activity of ginsenoside Ro.

Ginsenoside Ro, an oleanane-type saponin has been screened for activity in experimental models of acute and chronic hepatitis. Ginsenoside Ro (50 and 200 mg/kg, p.o.) inhibited the increase of serum glutamic oxaloacetic transaminase (s-GOT) and serum glutamic pyruvic transaminase (s-GPT) levels in D-galactosamine (GalN)- and carbon tetrachloride (CCl4)-induced acute hepatitic rats. Ginsenoside Ro inhibited the increase of connective tissue in the liver of CCl4-induced chronic hepatitic rats. Ginsenoside Ro showed a stronger inhibitory effect on the GalN-induced acute hepatitic model than those of the aglycone of ginsenoside Ro, oleanolic acid, or glycyrrhizic acid and its aglycone, glycyrrhetinic acid.

Hepatoprotective activity of andrographolide against galactosamine & paracetamol intoxication in rats.

Hepatoprotective effect of andrographolide (the major active diterpenoid lactone of the plant Andrographis paniculata) was studied on acute hepatitis induced in rats by single dose of galactosamine (800 mg/kg, ip)/paracetamol (3g/kg, po). Hepatoprotective activity was monitored by estimating the serum transaminases (GOT and GPT), alkaline phosphatase and bilirubin in serum, hepatic triglycerides, and by histopathological changes in the livers of experimental rats. Pre-treatment and/or post-treatment of rats at different time intervals with different doses of andrographolide in the two experimental models of hepatotoxicity showed that treatment of rats with 400 mg/kg, ip or 800 mg/kg, po, 48, 24 and 2 h before galactosamine administration or with 200 mg/kg, ip, 1, 4 and 7 h after paracetamol challenge leads to complete normalisation of toxin-induced increase in the levels of all the five biochemical parameters, and significantly ameliorates toxin-induced histopathological changes in the livers of experimental rats. The results confirmed the in vivo hepatoprotective effect of andrographolide against galactosamine or paracetamol-induced hepatotoxicity in rats. Since the protective effect of andrographolide was observed in two types of intoxication, which are very different in their primary mechanism of inducing hepatotoxicity, it is suggested that protective mechanisms of andrographolide which are not specific to galactosamine or paracetamol toxicity may be responsible for the hepatoprotective activity of the compound.

Influencia de la prednisona y extractos de Aloe barbadensis sobre la hepatitis experimental producida por galactosamina en ratas: estudio ultraestructural / Influence of prednisone and extracts of Aloe barbadensis on experiental hepatitis produced by galactosamine in rats: ultrastructural study

El efecto hepatotóxico de la galactosamina (GAS-N) en el modelo experimental en ratas ha sido estudiado al microscopio electrónico por varios autores. Por otra parte, en nuestro Instituto se realizó una investigación con este modelo experimental para probar el efecto de 2 extractos de la planta Aloe barbadensis obtenida por diferentes procedimientos. Aloe A y Aloe E. y un fármaco conocido, la prednisona: la efectividad de dichos extractos se ha demostrado en el orden siguiente: prednisona > Aloe E > Aloe A. Nuestro trabajo es un estudio complementario de dicha investigación al microscopio electrónico. Se utilizaron ratas albinas machos adultos de 160-180 g peso. el experimento constó de 5 grupos de ratas: control (normal), Gal N, Aloe A. Aloe E. y prednisona. Las muestras se procesaron por la técnica habitual para microscopía electrónica de transmisión: fijados en glutaraldehido y osmio e incluídas en araldita. En el grupo Gal N se observaron las alteraciones citoplasmáticas descritas por varios autores; existió un predominio de abundantes vacuolas lipídicas, hipertrofia del retículo endoplasmático (RE) liso, vacuolas autofágicas y estructuras polimembranosas; se observaron menos acentuados estas alteraciones en el grupo Aloe A., mejor cuadro ultraestructural en el grupo Aloe E, y fue muy semejante al normal en el grupo prednisona

Influencia de la prednisona y extractos de Aloe barbadensis sobre la hepatitis experimental producida por galactosamina en ratas: estudio ultraestructural / Influence of prednisone and extracts of Aloe barbadensis on experimental hepatitis produced by galactosamine in rats: ultrastructural study

El efecto hepatotóxico de la galactosamina (GAS-N) en el modelo experimental en ratas ha sido estudiado al microscopio electrónico por varios autores. Por otra parte, en nuestro Instituto se realizó una investigación con este modelo experimental para probar el efecto de 2 extractos de la planta Aloe barbadensis obtenida por diferentes procedimientos. Aloe A y Aloe E. y un fármaco conocido, la prednisona: la efectividad de dichos extractos se ha demostrado en el orden siguiente: prednisona > Aloe E > Aloe A. Nuestro trabajo es un estudio complementario de dicha investigación al microscopio electrónico. Se utilizaron ratas albinas machos adultos de 160-180 g peso. el experimento constó de 5 grupos de ratas: control (normal), Gal N, Aloe A. Aloe E. y prednisona. Las muestras se procesaron por la técnica habitual para microscopía electrónica de transmisión: fijados en glutaraldehido y osmio e incluídas en araldita. En el grupo Gal N se observaron las alteraciones citoplasmáticas descritas por varios autores; existió un predominio de abundantes vacuolas lipídicas, hipertrofia del retículo endoplasmático (RE) liso, vacuolas autofágicas y estructuras polimembranosas; se observaron menos acentuados estas alteraciones en el grupo Aloe A., mejor cuadro ultraestructural en el grupo Aloe E, y fue muy semejante al normal en el grupo prednisona

A novel biologically active seleno-organic compound--VI. Protection by ebselen (PZ 51) against galactosamine/endotoxin-induced hepatitis in mice.

Male albino NMRI mice were given 700 mg/kg galactosamine and 33 micrograms/kg salmonella endotoxin intraperitoneally. After 9 hr, serum sorbitol dehydrogenase activity had risen from 60 to 7320 U/l, SGOT from 90 to 5580, and SGPT from 70 to 10,440. When a similar dose of galactosamine alone or endotoxin alone was given, no significant liver injury was found. Animals pre-treated with an oral dose of ebselen (600 mg/kg 1-3 hr before galactosamine/endotoxin administration) were fully protected against this type of hepatitis. When pretreated 1 hr before intoxication with different doses of ebselen, significant dose-dependent reduction of serum enzyme activities was observed at doses higher than 1 mg/kg. After pre-treatment with 6 mg/kg ebselen, no biochemical or histological signs of liver lesions were detectable 36 hr after intoxication. In order to comparatively evaluate the model used, several established anti-inflammatory drugs were administered at doses which showed 50% effectiveness in preventing carageenan paw edema. A dose of 200 micrograms/kg dexamethasone, or 9 mg/kg indomethacin abolished galactosamine/endotoxin-induced enzyme release in our animals, as did the lipoxygenase pathway inhibitor diethylcarbamazine (78 mg/kg). In contrast, administration of cyclooxygenase pathway inhibitors such as aspirin (220 mg/kg) or ibuprofen (45 mg/kg) failed to prevent hepatitis. The effect of ebselen was also investigated in four different models of acute drug-induced liver damage. A dose of 600 mg/kg of the organic selenium compound was ineffective or weakly active in benzo(alpha)pyrene- or phenobarbital-treated mice which were intoxicated by intraperitoneal administration of 350 or 400 mg/kg body weight of paracetamol. Similarly negative results were obtained against bromobenzene-induced hepatotoxicity (520 mg/kg bromobenzene i.p.), carbon tetrachloride intoxication (3.2 g/kg), or allyl alcohol-induced liver damage (60 mg/kg). The selective efficacy of ebselen against galactosamine/endotoxin induced liver damage is interpreted in terms of its recently recognized ability to inhibit the formation of leukotrienes.