Hepatoprotective effects of propolis extract on carbon tetrachloride-induced liver injury in rats

The effects of an ethanolic extract of Cuban red propolis were examined using the model of acute hepatotoxicity induced by carbon tetrachloride (CCL₄) in rats. Propolis extract at doses of 5, 10 and 25 mg/kg i.p. decreased significantly the activity of alanine aminotransferase and the concentration of malondialdehyde in rat serum as well as the concentration of triglycerides in liver which were increased in CCI₄-treated animals. An ethanol extract of red propolis also reduced liver damage induced by CCI₄ in rats. This effect was observed by electron microscopy. According to our results it is concluded that ethanolic extract of red propolis exerts hepatoprotective effects in this experimental model which are probably caused by antioxidative properties (e.g. scavenging action against oxygen radicals) of this extract.     

Hepatoprotective effects and mechanisms of dehydrocavidine in rats with carbon tetrachloride-induced hepatic fibrosis

Aim of the study

The current study was designed to examine the effects and possible mechanisms of dehydrocavidine (DC) on carbon tetrachloride (CCl4)-induced hepatic fibrosis in male Sprague-Dawley (SD) rats.

Materials and methods

Hepatic fibrosis was induced in male rats with CCl4 administration for 12 weeks. Liver histopathological study was performed, and the liver function was examined by determining the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and total bilirubin (TBIL) for evaluating the effect of DC on hepatic fibrosis. The possible mechanisms were investigated by measuring hepatic collagen metabolism and oxidative stress level. Furthermore, oligo microarray analysis of 263 genes was performed, and quantitative real-time RT-PCR was used to verify 4 of the abnormally expressed genes (Bcl2, Cyp3a13, IL18 and Rad50).

Results

DC treatment significantly inhibited the loss of body weight and the increase of liver weight induced by CCl4. DC also improved the liver function of rats as indicated by decreased serum enzymatic activities of ALT, AST, ALP and TBIL. Histopathological results indicated that DC alleviated liver damage and reduced the formation of fibrous septa. Moreover, DC significantly decreased liver hydroxyproline (Hyp) and increased urine Hyp. It also decreased liver malondialdehyde concentration, increased activities of liver superoxide dismutase, catalase and glutathione peroxidase. Microarray analysis revealed that DC altered the expression of genes related to apoptosis, cytokines and other proteins involved in tissue repair.

Conclusions

Our findings indicate that DC can protect rats from CCl4-induced hepatic fibrosis through reducing oxidative stress, promoting collagenolysis, and regulating fibrosis-related genes.     

Trianthema portulacastrum affords antihepatotoxic activity against carbon tetrachloride-induced chronic liver damage in mice: reflection in subcellular levels

The efficacy of an ethanol extract of Trianthema portulacastrum as a hepatoprotective agent was investigated against carbon tetrachloride (CCl₄)-induced chronic liver injury in mice. The CCl₄ was administered per os (p.o.) three times a week for 5 weeks. Daily administration (p.o.) of T. portulacastrum plant extract at 100 or 150 mg/kg was started 2 weeks before the commencement of CCl₄ treatment and it continued during the entire period of the treatment. The extract dose-dependently decreased the activities of serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, alkaline phosphatase, glutamate dehydrogenase and sorbitol dehydrogenase as well as serum levels of bilirubin and urea which were otherwise significantly elevated with the chronic CCl₄ regimen alone. There was a substantial increase in the activities of plasma membrane enzymes γ-glutamyl transpeptidase and 5′-nucleotidase and lysosomal enzymes acid phosphatase and acid ribonuclease in hepatic tissue following CCl₄ treatment. These changes were reversed towards normalization with the extract in a dose-dependent manner. The extract also restored CCl₄-induced inhibition of hepatic microsomal enzyme glucose-6-phosphatase. The activities of mitochondrial succinate dehydrogenase and adenosine 5′-triphosphatase which were significantly attenuated by CCl₄ administration remained unaltered following the extract therapy. Results of this study provide evidence that the extract possesses a marked liver protective action which is comparable to that of silymarin, a standard hepatoprotective drug. The probable mechanism by which this plant exerts cytoprotection has also been discussed. © 1997 John Wiley & Sons, Ltd.     

Effect of schisandrin B and sesamin mixture on CCl(4)-induced hepatic oxidative stress in rats

To study the effects of schisandrin B and sesamin mixture on carbon tetrachloride (CCl(4))-induced hepatic oxidative stress in male Sprague-Dawley rats. The rats were randomly assigned to five groups: control group (olive oil injection), CCl(4) group (CCl(4) injection), silymarin group (CCl(4) injection combined with supplementation of silymarin, 7.5 mg/kg/day), low dose group (CCl(4) injection combined with supplementation of schisandrin B and sesamin mixture at a low dose, 43 mg/kg/day) and high dose group (CCl(4) injection combined with the supplementation of schisandrin B and sesamin mixture at a high dose, 215 mg/kg/day). The hepatic superoxide dismutase and glutathione peroxidase activities of rats in the low dose and high dose groups were increased significantly compared with those in the CCl(4) group. The hepatic reduced glutathione concentration in the silymarin, low dose and high dose groups were increased significantly (48%, 45% and 53%, respectively) when compared with those of the CCl(4) group. In addition, the concentration of glutathione in the erythrocytes of the low dose group was significantly higher than the CCl(4) group by 25%. These results suggest that the schisandrin B-sesamin mixture exerted a hepatoprotective effect by improving the antioxidative capacity in rats under CCl(4)-induced hepatic oxidative stress.     

Evaluation of hepatoprotective effect of Amalkadi Ghrita against carbon tetrachloride-induced hepatic damage in rats

Amalkadi Ghrita (AG), a polyherbal formulation, was evaluated for its hepatoprotective activity against carbon tetrachloride (CCl₄)-induced hepatic damage in rats. The hepatoprotective activity of AG was evaluated by measuring levels of serum marker enzymes like serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), and acid phosphatase (ACP). The serum levels of total proteins and bilirubin were also estimated. The histological studies were also carried out to support the above parameters. Silymarin was used as standard drug. Administration of AG (100 and 300 mg/kg, p.o.) markedly prevented CCl₄-induced elevation of levels of serum GPT, GOT, ACP, ALP, and bilirubin. The decreased level of total proteins due to hepatic damage induced by CCl₄ was found to be increased in AG-treated group. The results are comparable to that of silymarin. A comparative histopathological study of liver exhibited almost normal architecture, as compared to CCl₄-treated group. Hepatoprotective effect of AG is probably due to combined action of all ingredients.     

Effect of celery (Apium graveolens) extracts on some biochemical parameters of oxidative stress in mice treated with carbon tetrachloride

Extracts of celery leaves and roots in ether, chloroform, ethyl acetate, n-butanol and water were evaporated to dryness and dissolved in 50% ethanol to make 10% (w[sol ]v) solutions. The potential protective action of the extracts was assessed by the corresponding in vitro and in vivo tests. In the in vitro experiments crude methanol extracts were tested as potential scavengers of free OH* and DPPH* radicals, as well as inhibitors of liposomal peroxidation (LPx). Analogous experiments were also carried out with the extracts of celery root, for comparison. The results obtained show that both the extracts of root and leaves are good scavengers of OH* and DPPH* radicals and reduce LPx intensity in liposomes, which points to their protective (antioxidant) activity. In vivo experiments were concerned with antioxidant systems (activities of GSHPx, GSHR, Px, CAT, XOD, GSH content and intensity of LPx) in liver homogenate and blood of mice after their treatment with extracts of celery leaves, or in combination with CCl4. On the basis of the results obtained it can be concluded that the examined extracts showed a certain protective effect. Of all the extracts the n-butanol extract showed the highest protective effect. Combined treatments with CCl4 and extracts showed both positive and negative synergism - inducing or suppressing the impact of CCl4 alone. The differences observed in the action of particular extracts are probably due to the different contents of flavonoids and some other antioxidant compounds.     

Protective effects of Zingiber officinale (Zingiberaceae) against carbon tetrachloride and acetaminophen-induced hepatotoxicity in rats

The effect of the ethanol extract of the rhizome of Zingiber officinale was tested against carbon tetrachloride (CCl(4)) and acetaminophen-induced liver toxicities in rats. Increases in serum and liver marker enzymes such as alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase as well as sorbitol and glutamate dehydrogenases were produced in normal rats that were not pretreated with the extract. However, extract-pretreated rats attenuated in a dose-dependent manner, CCl(4) and acetaminophen-induced increases in the activities of ALT, AST, ALP, LDH and SDH in the blood serum. The protective effect of the extract on CCl(4) and acetaminophen-induced damage was confirmed by histopathological examination of the liver. These results indicate that the oil from the rhizome of Zingiber officinale could be useful in preventing chemically induced acute liver injury.     

Effect of the aqueous extract of Syzygium cumini on carbon tetrachloride-induced hepatotoxicity in rats

The aim of this study was to evaluate the effect of the aqueous Syzygium cumini leaf extract, given either as a single dose or by 7 days of pretreatment, on hepatotoxicity induced by carbon tetrachloride in rats. Blood samples obtained after treatments were measured for aspartate aminotransferase (AST) and alanine aminotransferase (ALT). A significant increase in the AST and ALT activities occurred after carbon tetrachloride administration alone, which was significantly lowered by preadministration with the aqueous extract of Syzygium cumini, but not by a single dose. This suggests that the extract may be useful for liver protection but needs to be given over a significant period and prior to liver injury.     

苦参素对大鼠慢性肝损伤的防护作用

目的 探讨苦参素对大鼠慢性肝损伤的影响。方法 用苦参素防治CCl4造成大鼠慢性肝损伤，并动态观察血清丙氨酸氨基转移酶（ALT）、IV型胶原（IV－C）、肿瘤坏死因子α（TNFα）的水平及肝组织病理变化。结果 大剂量苦参素治疗组血清ALT、IV－C、TNFα水平及肝组织内炎症活动度、纤维组增生程度均明显低于模型组（P＜0．05，0．01）。结论 苦参素对CCl4引起的大鼠慢性肝损伤具有一定的防护作用。     

Protective effects of dehydrocavidine on carbon tetrachloride-induced acute hepatotoxicity in rats

AIM OF THE STUDY: To investigate the protective effects of dehydrocavidine (DC), a main active ingredient of Corydalis saxicola Bunting (Yanhuanglian), on carbon tetrachloride (CCl4)-induced hepatotoxicity and the possible mechanisms involved in male Sprague-Dawley rats. MATERIALS AND METHODS: Acute hepatotoxicity was induced by CCl4 intoxication in rats. Serum biological analysis, lipid peroxides and antioxidants estimation, histopathological studies were carried out. RESULTS: Both pre-treatment with DC prior to CCl4 administration and post-treatment with DC after CCl4 administration significantly prevented increases in serum enzymatic activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and total bilirubin (TBIL). In addition, pre- and post-treatment with DC also significantly prevented formation of hepatic malondialdehyde (MDA), depletion of glutathione peroxidase (GPx) and depression of superoxide dismutase (SOD) in the liver of CCl4-intoxicated rats. ALT, AST, LDH, ALP and TBILL levels, as well as MDA, SOD and GPx activities were unaffected in normal rats by treatment with DC alone. GST, a phase II enzyme, had no significant changes during our experiments. Histopathological changes induced by CCl4 were also significantly attenuated by DC treatment in both preventive and curative experiments. CONCLUSIONS: DC has a potent hepatoprotective effect on CCl4-induced liver injury in rats through its antioxidant activity.     

The role of Urtica dioica and Nigella sativa in the prevention of carbon tetrachloride-induced hepatotoxicity in rats

The role of Nigella sativa L. (Ranunculaceae) (NS) and Urtica dioica L. was investigated (UD) in the prevention of carbon tetrachloride (CCl4) induced liver fibrosis and cirrhosis. Fifty Sprague-Dawley rats were allocated into fi ve groups (I, IIA and B, IIIA and B) and CCl4 was injected biweekly to all groups. Group I (control, CCl4 only), group IIA and B (NS fixed oil and volatile oil), group IIIA and B (UD fixed oil and UD decoction extract) rats were killed at the end of week 12 and histopathological and immunohistochemical examinations of liver tissues were performed. In the control group, coagulation necrosis and hydropic degeneration were marked in the periacinar regions (zone 3) associated with fibrosis in the periacinar regions and in the portal tracts. In groups IIA-B and IIIA-B (NS and UD), none of the serious histopathological findings were detected except for sparse coagulation necrosis in the periacinar regions. ASMA-positive perisinusoidal cells with myo fibroblastic transformation and lysosomal enzyme activity suggesting fibrogenesis were also significantly more common in the control group than in the NS and UD groups. UD and NS seem to be significantly effective in the prevention of carbon tetrachloride induced hepatotoxicity in rats.     

灯盏花素对四氯化碳小鼠肝损伤的保护作用

目的探讨灯盏花素对四氯化碳(CCl4)肝脏损伤的保护作用.方法小鼠腹腔注射0.1% CCl4 10ml/kg 造成肝损伤模型,以血清丙氨酸氨基转移酶(ALT)、肝匀浆谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量为指标观察灯盏花素对肝脏损伤的保护作用.结果灯盏花素50mg、100mg/kg·d ig×7d能明显降低CCl4中毒小鼠的血清ALT含量和肝匀浆MDA含量,提高肝脏GSH-Px活性.结论灯盏花素具有明显的保护肝作用,可通过增强抗氧化能力拮抗四氯化碳的肝毒性.     

Hepatoprotective effect of Vitis vinifera L. leaves on carbon tetrachloride-induced acute liver damage in rats

The hepatoprotective effect of ethanolic extract and its four different fractions (CHCl(3), EtOAc, n-BuOH, and remaining water fraction) of Vitis vinifera L. leaves was investigated against carbon tetrachloride (CCl(4))-induced acute hepatotoxicity in rats. The ethanolic extract was found active at 125mg/kg dose (per os). The ethanolic extract was fractionated through successive solvent-solvent extractions and the n-BuOH fraction in 83mg/kg dose possessed remarkable antioxidant and hepatoprotective activities. Liver damage was assessed by using biochemical parameters (plasma and liver tissue MDA [malondialdehyde], transaminase enzyme levels in plasma [AST-aspartate transaminase, ALT-alanine transferase] and liver GSH [glutathione] levels). Additionally, the pathological changes in liver were evaluated by histopathological studies. Legalon 70 Protect was used as standard natural originated drug.     

柴胡总皂苷粗提物致大鼠肝毒性及氧化损伤机制相关性研究

目的:观察长期、大量给予柴胡总皂苷粗提物导致大鼠肝毒性损伤程度及与氧化损伤机制的相关性。方法:按45 d毒性试验方法,给大鼠灌胃柴胡总皂苷粗提物,按柴胡总皂苷计算,高、中、低剂量组分别为100,50,10 mg.kg-1,45 d后观察一般状况,检测肝功能相关指标,检测血和肝组织内脂质代谢情况、糖代谢、胆红素(TBIL)水平和肝组织病理检查;检测血中总巯基(-SH)的量和血、肝组织内丙二醛(MDA)水平、超氧化物歧化酶(SOD)活性、谷胱甘肽(GSH)和谷胱甘肽过氧化物酶(GSH-Px)的量和活性。结果:柴胡总皂苷粗提物可导致血中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性增高,肝脏重量和肝体比值增大,血和肝内TG含量增加,对血中胆固醇(CHO)和肝内糖原(Gn)影响不明显,仅高剂量组对TBIL有影响;病理组织学检查可见肝细胞损伤。可导致血中总-SH的量增加;血和肝内MDA水平、GSH含量增加,SOD,GSH-Px活性下降。上述变化随剂量的增加而逐渐加重,与蒸馏水对照组比较有明显差异。结论:柴胡总皂苷粗提物可导致大鼠明显的肝毒性损伤,其损伤途径与氧化损伤机制有关。     

Amelioration of oxidative stress by dandelion extract through CYP2E1 suppression against acute liver injury induced by carbon tetrachloride in sprague‐dawley rats

The protective effects of common dandelion leaf water extract (DLWE) were investigated by carbon tetrachloride (CCl₄) induced hepatitis in Sprague‐Dawley rats. The animals were divided into five groups: normal control, DLWE control, CCl₄ control, and two DLWE groups (0.5 and 2 g/kg bw). After 1 week of administering corresponding vehicle or DLWE, a single dose of CCl₄ (50% CCl₄/olive oil; 0.5 mL/kg bw) was administered 24 h before killing in order to produce acute liver injury. The DLWE treatment significantly decreased CCl₄‐induced hepatic enzyme activities (AST, ALT and LDH) in a dose dependent manner. Also, the obstructed release of TG and cholesterol into the serum was repaired by DLWE administration. Hepatic lipid peroxidation was elevated while the GSH content and antioxidative enzyme activities were reduced in the liver as a result of CCl₄ administration, which were counteracted by DLWE administration. Furthermore, the hepatocytotoxic effects of CCl₄ were confirmed by significantly elevated Fas and TNF‐? mRNA expression levels, but DLWE down‐regulated these expressions to the levels of the normal control. Highly up‐regulated cytochrome P450 2E1 was also lowered significantly in the DLWE groups. These results indicate that DLWE has a protective effect against CCl₄‐induced hepatic damage with at least part of its effect being attributable to the attenuation of oxidative stress and inflammatory processes resulting from cytochrome P450 activation by CCl₄. Copyright © 2010 John Wiley & Sons, Ltd.     

不同柴胡组分对大鼠肝毒性与氧化损伤机制影响的研究

目的：比较柴胡不同组分对大鼠肝毒性损伤程度和氧化损伤机制的影响。方法：给大鼠灌胃柴胡醇提和水提组分,柴胡醇提和水提组分按等生药量计算,高、中、低剂量组分别为10.0,5.0,2.5 g·kg^-1,30 d后观察一般状况,检测肝功相关指标、血中总巯基(-SH)、血和肝组织内丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、谷胱甘肽(GSH)和谷胱甘肽过氧化物酶(GSH-Px)的含量和活性。结果：醇提和水提柴胡组分均可导致血中谷丙转氨酶(ALT)、谷草转氨酶(AST)活性增高,肝脏质量增加、肝体比值增大,血中总-SH含量降低,血和肝组织内MDA含量增加,GSH含量降低,SOD和GSH-Px的活性下降;上述变化随剂量增加而逐渐加重,与蒸馏水对照组相比有明显差异。结论：柴胡不同组分均可导致大鼠肝毒性损伤,其途径与过氧化损伤机制有关;且醇提组分的肝毒性损伤程度高于水提组分。     

Contribution of the antilipid peroxidative action of Dai-saiko-to extract to its preventive effect on carbon tetrachloride-induced acute liver injury in rats

Post-oral administration of Dai-saiko-to extract (TJ-8), a traditional herbal medicine, ameliorated acute liver injury in rats intoxicated with carbon tetrachloride (CCl₄). This TJ-8 administration inhibited an increase in lipid peroxide contents in the liver homogenate and microsomal fraction and a decrease in glucose-6-phosphatase activity in the liver microsomal fraction, an index of lipid peroxidation-mediated damage in liver microsomes, during the progression and recovery of the liver injury. These results indicate that the antilipid peroxidative action of TJ-8 contributes to its preventive effect on CCl₄-induced acute liver injury in rats. © 1998 John Wiley & Sons, Ltd.     

草苁蓉水萃取物对四氯化碳致肝损伤小鼠肝脏氧化应激的干预作用

目的:研究草苁蓉水萃取物(BRAF)对四氯化碳(CCl4)诱发的急性肝损伤小鼠肝脏氧化应激的干预作用.方法:将实验小鼠随机分为对照组、模型组、水飞蓟素阳性对照组(50 mg· kg-1)及BRAF高、低剂量组(200,100 mg·kg-1).每日给小鼠灌胃水飞蓟素或BRAF 1次,共7d.实验末期,腹腔注射CCl4建立小鼠急性肝损伤模型,苏木素-伊红(HE)染色法观察肝组织病理学变化,比色法检测血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)活性及肝脏超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)、Na+-K+-ATP酶(Na+-K+-ATPase)、Ca2+-Mg2+-ATP酶(Ca2+-Mg2+-ATPase)活性及还原型谷胱甘肽(GSH)、丙二醛(MDA)含量.结果:BRAF明显降低CCl4致急性肝损伤小鼠血清ALT,AST和ALP水平,减轻肝组织损伤,升高肝脏SOD,CAT,GPx和GSH水平,升高肝线粒体SOD,Na+-K+-ATPase和Ca2+-Mg2+-ATPase活性,降低肝匀浆及线粒体MDA含量.结论:BRAF降低CCl4致急性肝损伤小鼠肝脏氧化应激,对CCl4致小鼠急性肝损伤具有保护作用.     

Lycium barbarum polysaccharides protect mice liver from carbon tetrachloride-induced oxidative stress and necroinflammation

Ethnopharmacological relevance

Lycium barbarum has been used as a traditional Chinese medicine to nourish liver, kidneys and the eyes.

Aim of the study

We investigated the protective mechanisms of Wolfberry, Lycium barbarum polysaccharides (LBP) in carbon tetrachloride (CCl₄)-induced acute liver injury.

Materials and methods

Mice were intraperitoneally injected with a 50 μl/kg CCl₄ to induce acute hepatotoxicity (8 h) and were orally fed with LBP 2 h before the CCl₄ injection. There were six experimental groups of mice (n = 7-8 per group), namely: control mice (vehicle only; 1 mg/kg LBP or 10 mg/kg LBP), CCl₄-treated mice and CCl₄ + LBP treated mice (1 mg/kg LBP or 10 mg/kg LBP).

Results

Pre-treatment with LBP effectively reduced the hepatic necrosis and the serum ALT level induced by CCl₄ intoxication. LBP remarkably inhibited cytochrome P450 2E1 expression and restored the expression levels of antioxidant enzymes. It also decreased the level of nitric oxide metabolism and lipid peroxidation induced by CCl₄. LBP attenuated hepatic inflammation via down-regulation of proinflammatory mediators and chemokines. Furthermore, LBP promoted liver regeneration after CCl₄ treatment. The protective effects of LBP against hepatotoxicity were partly through the down-regulation of nuclear factor kappa-B activity.

Conclusion

LBP is effective in reducing necroinflammation and oxidative stress induced by a chemical toxin, thus it has a great potential use as a food supplement in the prevention of hepatic diseases.     

Antihepatotoxic effect of Nymphaea stellata willd., against carbon tetrachloride-induced hepatic damage in albino rats

Nymphaea stellata willd., a medicinal plant mentioned in Ayurveda for the treatment of liver disorders, has not been subjected to systematic scientific investigations to asses its hepatoprotective effects. Therefore, the present study was undertaken to investigate the hepatoprotective activity of extract of Nymphaea stellata willd., flower against carbon tetrachloride-induced hepatic damage in albino rats. The oral administration of varying dosage of extract of Nymphaea stellata willd., flower to rats for 10 days afforded the good hepatoprotection against carbon tetrachloride-induced elevation in serum marker enzymes, serum bilirubin, liver lipid peroxidation and reduction in liver glutathione, liver glutathione peroxidase, glycogen, superoxide dismutase and catalase activity.