Effect of mycophenolate mofetil alleviates carbon tetrachloride-induced liver fibrosis in mice / 中南大学学报(医学版)

OBJECTIVES@#Hepatic fibrosis is a serious pathological consequence of chronic liver disease. Mycophenolate mofetil (MMF) is a commonly used immunosuppressant after organ transplant. However, the relationship between MMF and hepatic fibrosis remains unclear. This study aims to explore the effect of MMF on hepatic fibrosis in mice and the potential mechanism.@*METHODS@#A total of 24 mice (male, 8-week old, C57BL/6) were randomly divided into a control group, a MMF group, a carbon tetrachloride (CCl4) group and a CCl4+MMF group (n=6 in each group). After the mice were sacrificed, the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected. The liver tissues were taken up for Masson staining and collagen I (COL1) immunohistochemistry. The levels of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) were detected by Western blotting. Finally, the levels of mRNA for TGF-β1, α-SMA, and COL1 were detected using real-time PCR.@*RESULTS@#Compared with the CCl4 group, the ALT and AST levels were lower (both P<0.05), the degree of liver fibrosis was alleviated, and the deposition of COL1 in the liver was significantly decreased (P<0.01) in the CCl4+MMF group. Compared with the CCl4 group, the protein expression levels of TGF-β1 and α-SMA were significantly decreased (both P<0.05) and the relative expression levels of TGF-β1, α-SMA and COL1 mRNA in the liver were significantly decreased (all P<0.05) in the CCl4+MMF.@*CONCLUSIONS@#MMF could reduce CCl4-induced hepatic fibrosis, which might be related to the inhibition of TGF-β1. This study is expected to provide a target for the treatment of hepatic fibrosis.

A study on the antioxidant activity of rosmarinic acid against carbon tetrachloride-induced liver toxicity in adult male albino rats / Estudio sobre la actividad antioxidante del ácido rosmarínico contra la toxicidad hepática inducida por tetracloruro de carbono en ratas albinas macho adultas

SUMMARY: Carbon tetrachloride (CCl4) is a manufactured chemical and does not occur naturally in the environment. CCl4 is a clear liquid that evaporates very easily. It has a sweet odor. CCl4 is toxic to the mammalian liver and is hepatocarcinogenic in both rats and mice. Rosemary (Rosmarinus Officinalis) is commonly used as a spice and flavoring agent in food processing. It is known for its antioxidant properties. The present study aims to investigate the antioxidant activity of rosmarinic acid (RA) on CCl4-induced liver toxicity in adult male albino rats. Forty adult male albino rats were divided into 4 groups with 10 rats in each group. Group I (control group). Group II animals received RA at a dose of 50 mg/kg/day by oral gavage for 4 weeks. Group III animals received CCl4 intraperitoneally at a dose of 3ml/kg twice weekly for 4 weeks. Group IV animals received CCl4 Plus RA. At the end of the experiment, liver specimens are processed for histological, immunohistochemical, EM and biochemical studies. Administration of RA deceased the elevated serum liver enzymes (AST, ALT, and ALP), elevated MDA level and immunoexpression of the proapoptotic protein (Bax) induced by CCl4. It increased reduced glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and immunoexpression of the antiapoptotic protein (Bcl2). It also improved the histological and ultrastructural changes induced by CCl4. It appears that Rosmarinic acid has protective effects against CCl4-induced hepatotoxicity as indicated by biochemical, histological, immunohistochemical and ultrastructural results.

RESUMEN: El tetracloruro de carbono (CCl4) es un producto químico fabricado y no se encuentra de forma natural en el medio ambiente. CCl4 es un líquido transparente que se evapora fácilmente; tiene un olor dulce. CCl4 es tóxico para el hígado de los mamíferos y es hepatocarcinogénico tanto en ratas como en ratones. El romero (Rosmarinus officinalis) se usa comúnmente como condimento y agente aromatizante en el procesamiento de alimentos. Es conocido por sus propiedades antioxidantes. El presente estudio tuvo como objetivo investigar la actividad antioxidante del ácido rosmarínico (RA) sobre la toxicidad hepática inducida por CCl4 en ratas albinas macho adultas. Se dividieron cuarenta ratas albinas macho adultas en 4 grupos con 10 ratas en cada grupo. Grupo I (grupo control). Los animales del grupo II recibieron AR a una dosis de 50 mg / kg / día por sonda oral durante 4 semanas. Los animales del grupo III recibieron CCl4 por vía intraperitoneal a una dosis de 3 ml / kg dos veces por semana durante 4 semanas. Los animales del grupo IV recibieron CCl4 Plus RA. Al final del experimento, las muestras de hígado se procesaron para estudios histológicos, inmunohistoquímicos, EM y bioquímicos. La administración de AR eliminó las enzimas hepáticas séricas elevadas (AST, ALT y ALP), el nivel elevado de MDA y la inmunoexpresión de la proteína proapoptótica (Bax) inducida por CCl4. Aumentó el glutatión reducido (GSH), glutatión peroxidasa (GSH-Px), la superóxido dismutasa (SOD) y la inmunoexpresión de la proteína antiapoptótica (Bcl2). También mejoró los cambios histológicos y ultraestructurales inducidos por CCl4. El ácido rosmarínico puede tener efectos protectores contra la hepatotoxicidad inducida por CCl4, tal como lo indican los resultados bioquímicos, histológicos, inmunohistoquímicos y ultraestructurales.

In vivo protective effect of cinnamon aqueous extract in carbon tetrachloride-treated male albino rats

The liver as an organ is important for the metabolism of drugs and toxins. However, it is not immune from environmental insults. Exposure of liver cells to carbon tetrachloride (CCl4) results in the generation of tricholoromethyl radicals, which induce liver toxicity. This study aims at investigating the ameliorative effect of the cinnamon aqueous extract (CAE) against CCl4-induced hepatotoxicity in male albino rats. Hepatotoxicity was induced in rats through the intraperitoneal administration of 0.5 mL kg-1body weight of CCl4. The analyses of the results obtained showed significant reduction in the levels of serum biochemical markers for 400 and 600 mg kg-1bw of CAE protected rats as compared with CCl4group. In addition, CAE administration reversed liver tissue damaged via increased antioxidants markers. Histopathological examination of CAE treatment on rats showed improved changes to the liver damage caused by CCl4 with no evidence of steatosis and inflammation. This result hence suggests that CAE has marked hepatoprotective and healing activities against CCl4-induced liver damage and could serve as a suitable candidate in drug discovery for the treatment of liver toxicity.

Stereological assessment of nephroprotective effects of Trachyspermum ammi essential oil against carbon tetrachloride-induced nephrotoxicity in mice / Evaluación estereológica de los efectos nefroprotectores del aceite esencial de Trachyspermum ammi contra la nefrotoxicidad inducida por tetracloruro de carbono en ratones

Trachyspermum ammi (T. ammi) has been used in folk medicine as anti-inflammatory, antipyretic, antibacterial, antifungal agent. The present study was conducted to investigate the protective effect of Trachyspermum ammi (T. ammi) essential oil against CC14- induced nephrotoxicity in mice. Thirty-five mice were divided into five groups as follows; positive control received olive oil 1 mL/ kg/ip, negative control received CC14 1 mg/kg/ip + 0.5 mL distilled water orally and tree treatment groups which received CC14 similar to the negative control and 200, 800 and 1600 µg/kg of T. ammi essential oil, respectively. All treatments were done twice a week (Saturday and Wednesday) for 45 days. On the last day, blood was sampled for urea and creatinine assessment and the left kidney was removed for stereological estimations. Essential oil of T. ammi at high dose significantly (p ≤ 0.05) decreased serum levels of creatinine and urea in comparison with CC14-treated group. Total volume of the kidney, cortex, proximal convoluted tubules (PC), glomerulus, vessels and interstitial tissue as well as total length of PC and vessel were significantly (p ≤ 0.05) increased following CC14 administration and were restored toward normal levels at high dose of T. ammi. Also, high dose of T. ammi improved glomerular loss significantly (p ≤ 0.05) as compared with CC14-treated group. Due to the chemical composition of T. ammi essential oil such as tymol, p-cymene, γ-terpinene which are antioxidant, it can be concluded that the essential oil of T. ammi can ameliorated renal injury induced following CC14 toxicity via its antioxidant components.

En la medicina popular se ha utilizado el aceite esencial de Trachyspermum ammi (T. ammi) como agente antiinflamatorio, antipirético, antibacteriano y anti fúngico. El presente estudio se realizó para investigar el efecto protector de Trachyspermum ammi (T. ammi) aceite esencial contra la nefrotoxicidad inducida en ratones. Treinta y cinco ratones fueron divididos en cinco grupos de la siguiente manera; el control positivo recibió 1 mL / kg / ip de aceite de oliva, el control negativo recibió 1 mg / kg / ip + 0,5 mL de agua destilada por vía oral y grupos de tratamiento arbóreo que recibieron un control similar al negativo y 200, 800 y 1600 mg / kg de T. aceite esencial de T. ammi, respectivamente. Todos los tratamientos se realizaron dos veces por semana (sábado y miércoles) durante 45 días. En el último día de tratamiento, se tomaron muestras de sangre para evaluar la urea y la creatinina, y se extrajo el riñón izquierdo para realizar estimaciones estereológicas. El aceite esencial de T. ammi a dosis altas significativamente (p ≤ 0,05) disminuyó los niveles séricos de creatinina y urea en comparación con el grupo tratado. El volumen total del riñón, la corteza, los túbulos contorneados proximales (PC), el glomérulo, los vasos y el tejido intersticial, así como la longitud total de la PC y el vaso aumentaron significativamente (p ≤ 0,05) después de la administración y se restablecieron a niveles normales con dosis altas de T. ammi. Además, una dosis alta de T. ammi mejoró significativamente la pérdida glomerular (p ≤ 0,05) en comparación con el grupo tratado. Debido a la composición química del aceite esencial de T. ammi como timol, p-cimeno, 𝛾-terpineno con propiedades antioxidantes, se puede concluir que el aceite esencial de T. ammi puede mejorar la lesión renal inducida después de la toxicidad a través de sus componentes antioxidantes.

Therapeutic efficacy of Nigella sativa Linn. seed extract against CCl4 induced hepatic injury in wistar rats.

Carbon tetrachloride (CCl4) intake damages liver. We evaluated therapeutic potential of aqueous extract of Nigella sativa seeds against CCl4 induced liver damage in rats. The hepatic damage induced by CCl4 @ 1.5 mL/kg, ip was evidenced by a significant increase in the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, protein and urea lipid peroxidation (LPO) as well as reduction in hepatic antioxidant system e.g. reduced glutathione. Hepatic total protein and glucose-6-phosphatase activity were found decreased. Histological studies substantiated the above biochemical findings. However, after 48 h of administration of aqueous extract of N. sativa seeds (250, 500 and 750 mg/kg, po) it not only detoxified the toxicity but also reversed LPO, GSH, AST, ALT and serum protein changes at all the three doses. Both higher doses of extract were found effective in monitoring urea, albumin, total protein and G-6-Pase activity. However, on the basis of percent protection highest dose i.e., 750 mg/kg proved better. The result suggests that the aqueous extract of N. sativa seeds can be used as a hepatoprotective agent.

Thalidomide Accelerates the Degradation of Extracellular Matrix in Rat Hepatic Cirrhosis via Down-Regulation of Transforming Growth Factor-beta1

PURPOSE: The degradation of the extracellular matrix has been shown to play an important role in the treatment of hepatic cirrhosis. In this study, the effect of thalidomide on the degradation of extracellular matrix was evaluated in a rat model of hepatic cirrhosis. MATERIALS AND METHODS: Cirrhosis was induced in Wistar rats by intraperitoneal injection of carbon tetrachloride (CCl4) three times weekly for 8 weeks. Then CCl4 was discontinued and thalidomide (100 mg/kg) or its vehicle was administered daily by gavage for 6 weeks. Serum hyaluronic acid, laminin, procollagen type III, and collagen type IV were examined by using a radioimmunoassay. Matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and alpha-smooth muscle actin (alpha-SMA) protein in the liver, transforming growth factor beta1 (TGF-beta1) protein in cytoplasm by using immunohistochemistry and Western blot analysis, and MMP-13, TIMP-1, and TGF-beta1 mRNA levels in the liver were studied using reverse transcriptase polymerase chain reaction. RESULTS: Liver histopathology was significantly better in rats given thalidomide than in the untreated model group. The levels of TIMP-1 and TGF-beta1 mRNA and protein expressions were decreased significantly and MMP-13 mRNA and protein in the liver were significantly elevated in the thalidomide-treated group. CONCLUSION: Thalidomide may exert its effects on the regulation of MMP-13 and TIMP-1 via inhibition of the TGF-beta1 signaling pathway, which enhances the degradation of extracellular matrix and accelerates the regression of hepatic cirrhosis in rats.

Protective effect of alcoholic extract of Entada pursaetha DC. against CCl4-induced hepatotoxicity in rats.

The alcoholic extract of stem of E. pursaetha (PSE, 30, 100, 300 mg/kg body weight, po for 7 days) showed hepatoprotective activity against CCl4 (2 mL/kg body weight, ip)-induced hepatotoxicity. The extract exhibited a significant dose-dependent hepatoprotective effect comparable to standard drug silymarin, by preventing increase in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, and total bilirubin, lactate dehydrogenase; by lowering hepatic levels of malonaldehyde, nitrate-nitrite, myeloperoxidase activity; enhancing activities of antioxidant enzymes, superoxide dismutase, catalase and increasing reduced glutathione levels in liver, which suggests the antioxidant property of PSE. Histopathological studies also supported the above biochemical parameters. The results suggested that alcoholic extract of E. pursaetha possesses significant hepatoprotective activity in CCl4-induced acute hepatotoxicity in rats and this is likely to be mediated through its antioxidant activities.

Antihepatotoxic effect of golden berry [Physalis peruviana Linn.] in carbon tetrachloride [CCl[4]] intoxicated rats

Liver is the main site in the body for intense metabolism and excretion. A number of chemicals and drugs which are used routinely cause liver damage. The present study investigates the antihepatotoxic effect of Physalis peruviana whole ripe fruit, water and ethanol extracts of fruit in normal as well as in carbon tetrachloride [CCl[4]] intoxicated rats. The CCl[4] treated rats showed marked elevation in liver enzymes: alanine transaminse, aspratate transaminase, alkaline phosphatase, lactate dehydrogenase and other biochemical parameters: bilirubin, creatinine and urea, thus indicating liver injury. Whereas animal treated/fed with various preparations of Physalis peruviana showed significant lowering effect [p<0.05] in the elevated levels of serum markers like ALAT, ASAT, ALP, LDH, creatinine, urea and bilirubin indicating the protection against hepatic cell damage. The water extract of Physalis peruviana showed highest activity in both rat models while ripe fruit and ethanol extract showed moderate activity compared to standard drug.

Mest Attenuates CCl4-Induced Liver Fibrosis in Rats by Inhibiting the Wnt/beta-Catenin Signaling Pathway

BACKGROUND/AIMS: The Wnt/beta-catenin signaling pathway has been reported to play an important role in liver fibrosis. This study was designed to investigate whether mesoderm-specific transcript homologue (Mest), a strong negative regulator of Wnt/beta-catenin signaling, could inhibit liver fibrosis. METHODS: pcDNA-Mest was transfected into hepatic stellate cells (HSCs) and rats. Rats were randomly divided into four groups: normal group (normal saline), treatment group (pcDNA-Mest+CCl4), control group (pcDNA-neo+CCl4), and model group (normal saline+CCl4). Changes in liver pathology were evaluated by hematoxylin and eosin and Masson's trichrome staining. The levels of alanine transaminase, aspartate transaminase, lactic dehygrogenase, hyaluronic acid, and laminin in the serum and hydroxyproline in the liver were detected by biochemical examination and radioimmunoassay, respectively. The expression and distribution of beta-catenin, alpha-smooth muscle actin (alpha-SMA), Smad3, and tissue inhibitor of metalloproteinase type I were determined, and the viability of the HSCs was tested. RESULTS: Our data demonstrate that Mest alleviated CCl4-induced collagen deposition in liver tissue and improved the condition of the liver in rats. Mest also significantly reduced the expression and distribution of beta-catenin, alpha-SMA and Smad3 both in vivo and in vitro, in addition to the viability of HSCs in vitro. CONCLUSIONS: We found that Mest attenuates liver fibrosis by repressing beta-catenin expression, which provides a new therapeutic approach for treating liver fibrosis.

Review of experimental models for inducing hepatic cirrhosis by bile duct ligation and carbon tetrachloride injection / Revisão de modelos experimentais de cirrose hepática induzida por ligadura do ducto biliar e por injeção de tetracloreto de carbono

PURPOSE: To present a review about a comparative study of bile duct ligation versus carbon tetrachloride Injection for inducing experimental liver cirrhosis. METHODS: This research was made through Medline/PubMed and SciELO web sites looking for papers on the content "induction of liver cirrhosis in rats". We have found 107 articles but only 30 were selected from 2004 to 2011. RESULTS: The most common methods used for inducing liver cirrhosis in the rat were administration of carbon tetrachloride (CCl4) and bile duct ligation (BDL). CCl4 has induced cirrhosis from 36 hours to 18 weeks after injection and BDL from seven days to four weeks after surgery. CONCLUSION: For a safer inducing cirrhosis method BDL is better than CCl4 because of the absence of toxicity for researches and shorter time for achieving it.

OBJETIVO: Apresentar revisão sobre estudo comparativo da indução de cirrose hepática (CH) experimental com a injeção de tetra-cloreto de carbono (CCl4) comparado à ligadura do ducto biliar (BDL). MÉTODOS: A pesquisa foi realizada nas bases de dados do Medline/PubMed e SciELO procurando trabalhos com as palavras indução de CH e ratos. Foram encontrados 107 artigos, mas somente 30 foram selecionados no período de 2004 à 2011. RESULTADOS: Os procedimentos mais comum para indução de CH em ratos foram a injeção de CCl4 e a BDL. O CCl4 induzia CH no período de 36 horas após a injeção e a DBL de sete dias à quatro semanas após a cirurgia. CONCLUSÃO: A BDL é o método mais seguro para indução de CH quando comparado a injeção de CCl4 pela ausência de toxicidade para os pesquisadores e o menor tempo para se obter a lesão hepática.

Protective Effect of Ethyl Acetate Extract of Acacia Catechu in Carbon Tetrachloride Induced Hepatotoxicity.

Objective: To study the protective effect of ethyl acetate extract of Acacia catechu in carbon tetrachloride induced hepatotoxicity in albino rats. Methods: The liver damage in albino rat was induced by a subcutaneous injection of 50%v/ v carbon tetrachloride in olive oil at the dose of 2ml/kg twice a week for 14days. The hepatoprotective activity was monitored biochemically by estimating serum transaminases, serum alkaline phosphatase, serum bilirubin and serum protein after intraperitoneal injection of ethyl acetate extract of Katha(250mg/kg). Silymarin(5mg/kg.I.P) was given as a reference drug. The histopathological changes of liver samples were compared with that of control. Results: Ethyl acetate extract of Acacia catechu inhibited carbon tetrachloride induced liver toxicity in albino rats at 250mg/kg body weight as assessed by the biochemical and histological examination. Conclusion: Ethyl acetate extract of “Katha” exhibited significant hepatoprotective activity.

Curative effect of bone marrow cells transplantation and/or low dose gamma irradiation on liver injuries induced by carbon tetrachloride

Liver is the most common target for toxic injury. Toxic agents include chemicals such as carbon tetrachloride [CCl4] and trichloroethylene. This study aimed to evaluate the effect of bone marrow cells [BMC] transplantation and/or fractionated low doses [0.5 Gy] gamma radiation on established liver fibrosis induced by CCl4. BMCs of male albino rats were transplanted into 4-weeks carbon tetrachloride [CCl4]-treated and/or fractionated low doses [0.5 Gy] gamma irradiated rats through the tail vein, and the rats were treated for 4 more weeks with CCl4 [total 8 weeks]. Histological and ultrastructural investigations revealed that both bone marrow cells transplantation and low dose [0.5 Gy] gamma radiation exposure with continuous CCl4 injection had reduced liver fibrosis as compared with rats treated with CCl4 alone

Hepatoprotective effect of otostegia persica boiss. shoot extract on carbon tetrachloride-induced acute liver damage in rats

In this study, the hepatoprotective effect of the methanol extract of aerial parts [shoot] from Otostegia persica Boiss [Golder] was investigated against the carbon tetrachloride [CCl[4]]-induced acute hepatotoxicity in male rats. Liver damage was induced through the oral administration of 50% CCl[4] in liquid paraffin [2.5 mL/Kg bw, per os] 60 min after the administration of the methanol extract of O. persica shoot [in 200, 300, 400 mg/Kg bw doses] and assessed using biochemical parameters [plasma and liver tissue malondialdehyde [MDA], transaminase enzyme levels in plasma [aspartate transaminase [AST], alanine aminotransferase [ALT]] and liver glutathione [GSH] levels]. Results show that the methanol extract of O. persica shoot is active at 300 mg/Kg [per os] and it possess remarkable antioxidant and hepatoprotective activities. Additionally, histopathological studies verified the effectiveness of this dose of extract in acute liver damage prevention

protective effect of lemon grass and its oil on hepatotoxicity in rats caused by CCL4

The present work was conducted to study the effect of lemon grass and its oil on the nutritional value, percent of organs weight/body weight, lipid parameters, glucose, iron status, kidney and liver functions of rats suffering from hepato-toxicity caused by CC1[4]. Six experimental groups [n = 6 for each group] were established. Groups [1 and 2] were fed on basal diets [used as a negative and positive control groups, respectively]. Groups [3- 4] received basal diets containing two levels of lemon grass [2.5 and 5g lemon grass/l00g diet, respectively]. Groups [5-6] received basal diets containing two levels of lemon grass oil [2.5 and 5g lemon grass/l00g diet, respectively]. Before 2 days from the end of the experiment period [28 days], all treated and positive control groups were injected with CC1[4], in paraffin oil [20% at dose 5 ml/kg] subcutaneous injection to induced hepatotoxicity in rats. Addition of lemon grass or its oil to the diets improved the nutritional value, in addition to the percent organs weight/ body weight. The mean values of serum cholesterol, triglycerides, low-density lipoprotein cholesterol [LDL-c], very low-density lipoprotein [VLDL-c], uric acid, urea nitrogen, creatinine, glucose, aspartate amino transferase [AST] and alanine amino transferase [ALT] decreased in all treated groups with lemon grass or its oil, as compared to the positive control groups, while high-density lipoprotein [HDL-c] increased. Histopathological examination of liver in group treated with CC1[4] revealed degenerative and necrotic changes, however, treated groups with lemon grass or its oil showed marked amelioration of the severity of these changes. It was concluded that high level of lemon grass or its oil [5g /l00g diet] realized the best effect on lipid profile, kidney and liver functions, glucose level and iron status

Impact of galectin-3 deficiency on gene expression in the liver of mice 48-h post-treatment with olive oil or CC1[4]

Galectin-3 [Gal-3] is a multifunctional protein, playing a key role in many biolegical processes. Previous study demonstrated that normal hepatocytes do not express galectin-3, but this protein can be present in injured liver. The present paper aimed to assist in elucidate the biological role of galectin-3 in injured liver by CC1[4] and to clarify genes that differentially expressed in response to galectin-3 deficiency in normal and chemically injured liver of mice 48-h post-treatment with olive oil or CC1[4]. Four male wild type mice [WT] and another four galectin-3 disrupted mice [Gal-3[-/-]] were used in this experiment. The mice were fasted overnight and classified into two groups, [each group including, two WT and two Gal-3[-/-] mice] the first subgroup received in the following morning 4 ml/kg olive oil, while the second subgroup was received 8 ml/kg CC1[4] [50% in olive oil] by gavages. After 48h, the mice were anesthetized and killed to obtain blood and excise the liver. Gene's expression analysis in the liver tissue was carried out using cDNA microarray technique. The cDNA microarrays analysis revealed that 7 genes have clearly changed their levels of expression, of these 5 genes related to detoxification mechanisms are up-regulated and 2 genes related to tumor cell and amyloid protein have been down-regulated in Gal-3[-/-] mice after 48 h post-treatment with olive oil. The mice treated with CC1[4] reveled that 42 genes have clearly changed their levels of expression, of this 8 genes were up-regulated and 34 genes were down-regulated. Of the up-regulated genes were detoxification, fatty acids and lipid metabolism proteins. On the other hand, the down-regulated genes encoded proteins for xenobiotic metabolism, stress response, transcription factors, lipid metabolism, proteolysis and peptedolysis, RNA, nerve system, and immune responses proteins. This study demonstrated that changes in gene expression profile in galectin-3 deficiency mice 48-h post-treatment with CC1[4], mostly related to down-regulated different genes including, many biological processes, implying the multifunctional of galectin-3 to protect and ameliorated the liver injury induced by CC1[4] in mice

[Protective effect of walnut [juglans regia L.] extract against CCI[4] - induced hepatotoxicity in rats]

Walnut [Juglans regia L.] is widely distributed all over the world. Dry seeds, [nuts], as well as green walnuts, shells, bark, green husks [epicarps] and leaves, have all been used in the cosmetic and pharmaceutical industries. In the present study, hepatoprotective potential of ethanolic extract of walnut leaves was investigated against carbon tetrachloride [CCl [4]] induced liver damage in rats. This experimental study was done on 36 rats divided into six groups. Adult male rats were orally administered different doses of walnut extract [50, 100, 200 and 400 mg/kg bw/daily] along with CCl [4] [50% CCl [4], in olive oil, 1 ml/kg, intrapertioneally] twice a week for 28 consecutive days. Biochemical parameters like alanine amino transferase, aspartate amino transferase, alkaline phosphatase and total protein levels in the serum were determined. Statistical analysis was carried out using ANOVA test. Administration of CCl [4] increased the serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase [p<0.01]. Treatment with the ethanolic extract of walnut leaves significantly decreased the above parameters [p<0.01]. Ethanolic extract of walnut leaves could protect liver against the CCl [4]-induced oxidative damage in rats, and this hepatoprotective effect might be due to modulation of toxic and oxidant enzymes and also to the scavenger effect on free radicals

Effect of benfotiamine on hepatic tissue levels of free calcium, copper, iron and zinc during CCI4-induced hepatotoxicity in rats

Toxic injury occurs in the liver more often than other organ, this can be attributed to the fact that virtually all ingested substances that are absorbed are first presented to the liver and that the liver is responsible for the metabolism and elimination of many substances. Carbon tetrachloride [CCI4] is very well known to cause hepatotoxicity that may be associated with impaired calcium and trace element homeostasis. This study was designed to evaluate the protective effect of benfotiamine against CCI4-induced disturbances in calcium, iron, copper and zinc homeostasis in liver tissue of rats. Liver tissue homogenate from normal controls, CCI4-treated and benfotiamine [70 mg/kg] pre-treated before induction of hepatic damage with CCI4 in rats were obtained, and processed for estimation of levels of free forms of calcium, iron, copper and zinc using atomic absorption spectrophotometry. Analysis of data revealed significant elevation in calcium, iron and copper levels in hepatic tissue due to exposure to CCI4 compared to controls, while zinc levels not significantly affected. Pretreatment with benfotiamine results in significant decrease in calcium, iron and copper levels compared to non-treated group, while zinc levels found to be significantly elevated. Benfotiamine has a protective effect against CCI4-induced hepatic tissue damage which may be, in part, attributed to restoration of calcium and other trace elements homeostasis

effects of cynara scolymus L. leaf and cichorium intybus L. root extracts on carbon tetrachloride induced liver toxicity in rats

Cynara scolymus and Cichorium intybus are popular herbal remedy in folk medicine for liver disorders. Although many experimental studies carried out, scientifically reliable data needed to verify minimum effective dosage and efficacy of these medicinal plants. In present investigation, the effects of C. scolymus leaf and C. intybus root extracts at different doses were tested against CCl[4] induced rats liver toxicity. The C. scolymus leaf and C. intybus root extracts at the doses of 300, 600 and 900 and 150, 300 and 450 mg/kg/day were prepared respectively. Liver intoxication was induced in 7 groups of rats by intraperitoneal injection of 1 ml/kg of 1:1 CCl[4] in olive oil for two successive days. One group kept as control and six different doses of plant extracts were administered to six groups simultaneously with CCl[4] administration. The serum levels of ALT, AST and ALP, liver tissue glutathione and catalase activity as well as liver tissue microvesicular steatosis [MVS] and pericentral coagulation necrosis [PCN] were determined after three days. The serum ALT, AST and ALP and liver tissue MVS were significantly reduced in both the C. scolymus and C. intybus groups at the doses of 900 and 450 mg/kg/day respectively while liver tissue PCN significantly reduced in C. scolymus 900 mg/kg/day group only as compared to control group. In present study administration of the C. scolymus leaf [900 mg/kg/day] and C. intybus root [450 mg/kg/day] extracts ameliorated CCl[4] induced rat serum liver enzyme changes and liver tissue histopathological damage

study on effects of glutathione s-transferase from silkworm on CCL[4]-induced mouse liver injury

To assess the hepatoprotective activity of Glutathione S-transferase [GSTsw], extracted and purified from silkworm, in experimental acute mice liver injury and explore mechanisms. Mice were divided into five groups: control group, carbon tetrachloride [CC1[4]] group, and three treatment groups that received CC1[4] and GSTsw at doses of 0.083mg-g[-1], 0.0415 mg-g[-1] and 0.0207 mg-g[-1] for 3 days. ALT in serum, GST, SOD and T-AOC in liver tissue homogenate, and changes in liver pathology in the five groups were studied. CC1[4] administration led to pathological and biochemical evidence of liver injury as compared to untreated controls. GSTsw administration led to significant protection against CCl[4]-induced changes in liver pathology. It was also associated with significantly lower serum ALT levels, higher GST - SOD and T-AOC level in live tissue homogenate. Thus, GSTsw showed protective activity against CCl[4]-induced hepatotoxicity in mice

Hepatoprotective activity of leaves of Zanthoxylum armatum DC in CCl4 induced hepatotoxicity in rats.

Zanthoxylum armatum DC (Rutaceae) is extensively used in indigenous system of medicine as a tonic, carminative, stomachic and anthelmintic. In the present study, the hepatoprotective activity of the leaves ethanolic extract of Z. armatum (EEZA) was evaluated in CCl4-induced hepatotoxicity in rats. The extract at a dose of 500 mg/kg registered a significant decrease in the levels of serum glutamyl oxalacetic acid transaminase (SGOT), serum glutamyl pyruvate transaminase (SGPT), alkaline phosphatase (ALKP), and serum bilurubin (SBLN) and liver inflammation, which was supported by histopathological studies on liver, thus exhibited a significant hepatoprotective activity. The phytochemical screening of defatted ethanolic extract showed the presence of sterols, alkaloids, flavonoids, and reducing sugars.