Hepatoprotective activity of Leucas hirta against CCl4 induced hepatic damage in rats

Methanol and aqueous leaf extracts of L. hirta demonstrated hepatoprotective activity against carbon tetrachloride induced liver damage in rats. The parameters studied were serum total bilirubin, total protein, alanine transaminase, aspartate transaminase and alkaline phosphatase activities. The hepatoprotective activity was also supported by histopathological studies of liver tissue. Results of the biochemical studies of blood samples of CCl4 treated animals showed significant increase in the levels of serum markers and decrease in total protein level reflecting the liver injury caused by CCl4. Whereas blood samples from the animals treated with methanol and aqueous leaf extracts showed significant decrease in the levels of serum markers and increase in total protein indicating the protection of hepatic cells. The results revealed that methanol leaf extract followed by aqueous extract of L. hirta could afford significant protection against CCl4 induced hepatocellular injury.     

重组人肝细胞生长因子抗四氯化碳染毒小鼠肝的保护效应

为检测重组人肝细胞生长因子（ｒ－ｈＨＧＦ）的保肝作用,本工作观察到ｒ－ｈＨＧＦ降低ＣＣｌ４染毒小鼠血清ＡＬＴ和ＡＳＴ升高的幅度,减轻肝组织受损的程度和防止肝细胞器的破坏,而且,ｒ－ｈＨＧＦ的这种保肝效应所需剂量极小,为ｎｇ级。根据上述资料推测,ｒ－ｈＨＧＦ为一极有效的保护小鼠肝抗ＣＣｌ４损伤的生长因子     

The effects of thromboxane A2 inhibitors (OKY-046 and ONO-3708) and leukotriene inhibitors (AA-861 and LY-171883) on CCl4-induced chronic liver injury in mice

The effects of OKY-046, a selective thromboxane A2 (TxA2) synthetase inhibitor, ONO-3708, a novel TxA2 receptor antagonist, AA-861, a selective 5-lipoxygenase inhibitor and LY-171883, a peptide leukotrienes (p-LTs) receptor antagonist on the chronic liver injury were investigated in mice. The chronic liver injury was induced by the injection of carbon tetrachloride (CCl4) two times a week for twelve weeks in mice. In chronic liver injury models, significant histopathological changes in the liver and extensive elevation of glutamate transaminase (GOT and GPT) activity were observed. Administration of OKY-046, ONO-3708, AA-861 and LY-171883 for 12 weeks suppressed the elevation of serum GOT and GPT levels and histopathological changes in CCl4-induced chronic liver injury. These results suggest that TxA2 and LTs inhibitors are effective for the onset and development of chronic liver injury in mice.     

Sake Yeast Suppresses Acute Alcohol-Induced Liver Injury in Mice

Brewer’s and baker’s yeasts appear to have components that protect from liver injury. Whether sake yeast, Saccharomyces cerevisiae Kyokai no. 9, also has a hepatoprotective effect has not been examined. Here we show that sake yeast suppresses acute alcoholic liver injury in mice. Male C57BL/6 mice that had been fed a diet containing 1% sake yeast for two weeks received three doses of ethanol (5 g/kg BW). In the mice fed sake yeast, ethanol-induced increases in triglyceride (TG) and glutamate pyruvate transaminase (GPT) were significantly attenuated and hepatic steatosis was improved. In addition, sake yeast-fed mice showed a smaller decrease in hepatic S-adenosylmethionine (SAM) level and a smaller increase in plasma homocysteine (Hcy) level after ethanol treatment than the control mice, suggesting that a disorder of methonine metabolism in the liver caused by ethanol was relieved by sake yeast. These results indicate that sake yeast protects against alcoholic liver injury through maintenance of methionine metabolism in the liver.     

Evaluation of hepatoprotective activity of Clerodendrum serratum L

The ethanol extract of C. serratum roots and ursolic acid isolated from it were evaluated for hepatoprotective activity against carbon tetrachloride induced toxicity in male Wistar strain rats. The parameters studied were estimation of liver function serum markers such as serum total bilirubin, total protein, alanine transaminase, aspartate transaminase and alkaline phosphatase activities. The ursolic acid showed more significant hepatoprotective activity than crude extract. The histological profile of the liver tissue of the root extract and ursolic acid treated animal showed the presence of normal hepatic cords, absence of necrosis and fatty infiltration as similar to the controls. The results when compared with the standard drug silymarin, revealed that the hepatoprotective activity of the constituent ursolic acid is significant as similar to the standard drug.     

Protective effect of Phyllanthus fraternus against carbon tetrachloride-induced mitochondrial dysfunction.

The effect of carbon tetrachloride administration on liver mitochondrial function and the protective effect of an aqueous extract of Phyllanthus fraternus were studied in rats. The following changes were observed in mitochondria due to the administration of carbon tetrachloride. 1) A decrease in the rate of respiration, respiratory control ratio and P/O ratio using glutamate and malate or succinate as substrates. 2) A decrease in the activities of NADH dehydrogenase (35%), succinate dehydrogenase (76%) and cytochrome c oxidase (51%). The rate of electron transfer through site I, site II and site III was studied independently and found to be significantly decreased. 3) A decrease in the content of cytochrome aa3 (34%). 4) A significant decrease in the levels of phospholipids particularly cardiolipin and a significant increase in the lipid peroxide level was observed. The carbon tetrachloride induced toxicity may be partly due to the lipid peroxidation and partly due to the effect on protein synthesis. Administration of rats with an aqueous extract of P. fraternus prior to carbon tetrachloride administration showed significant protection on the carbon tetrachloride induced mitochondrial dysfunction on all the parameters studied.     

Hepatoprotective and antioxidant activities of flowers of Calotropis procera (Ait) R. Br. in CCl4 induced hepatic damage

Hepatoprotective activity of 70% ethanolic extract of flowers of C. procera was studied against CCl4 induced hepatic injury in albino rats and mice. In addition, antioxidant activity was studied by in vitro models. Pre-treatment with 70% ethanolic extract (CPA) reduced the biochemical markers of hepatic injury like serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, bilirubin, cholesterol, HDL and tissue glutathione (GSH) levels. Similarly pretreatment with CPA reduced the CCl4 induced elevation in the pentobarbitone sleeping time. Histopathological observations also revealed that pretreatment with CPA protected the animals from CCl4 induced liver damage. CPA demonstrated dose dependant reduction in the in vitro and in vivo lipid peroxidation induced by CCl4. In addition it showed dose dependant free radical scavenging activity. The results indicate that flowers of C. procera possess hepatoprotective property possibly because of its anti-oxidant activity. This property may be attributed to the quercetin related flavonoids present in the flowers of Calotropis procera.     

Adenosine 2A Receptor Antagonist Prevented and Reversed Liver Fibrosis in a Mouse Model of Ethanol-Exacerbated Liver Fibrosis

The effect of moderate alcohol consumption on liver fibrosis is not well understood, but evidence suggests that adenosine may play a role in mediating the effects of moderate ethanol on tissue injury. Ethanol increases the concentration of adenosine in the liver. Adenosine 2A receptor (A2AR) activation is known to enhance hepatic stellate cell (HSC) activation and A2AR deficient mice are protected from fibrosis in mice. Making use of a novel mouse model of moderate ethanol consumption in which female C57BL/6J mice were allowed continued access to 2% (vol/vol) ethanol (11% calories) or pair-fed control diets for 2 days, 2 weeks or 5 weeks and superimposed with exposure to CCl₄, we tested the hypothesis that moderate ethanol consumption increases fibrosis in response to carbon tetrachloride (CCl₄) and that treatment of mice with an A2AR antagonist prevents and/or reverses this ethanol-induced increase in liver fibrosis. Neither the expression or activity of CYP2E1, required for bio-activation of CCl₄, nor AST and ALT activity in the plasma were affected by ethanol, indicating that moderate ethanol did not increase the direct hepatotoxicity of CCl₄. However, ethanol feeding enhanced HSC activation and exacerbated liver fibrosis upon exposure to CCl_4. This was associated with an increased sinusoidal angiogenic response in the liver. Treatment with A2AR antagonist both prevented and reversed the ability of ethanol to exacerbate liver fibrosis.

Conclusion

Moderate ethanol consumption exacerbates hepatic fibrosis upon exposure to CCl₄. A2AR antagonism may be a potential pharmaceutical intervention to decrease hepatic fibrosis in response to ethanol.     

茵陈保肝活性部位的初步筛选研究

目的:筛选茵陈发挥保肝作用的有效部位.方法:用系统溶剂分离法将茵陈分离成极性不同的组分.采用四氯化碳(CCl4)致小鼠急性肝损伤模型,按赖氏法测定小鼠血清中AST,ALT的活性.结果:茵陈的三氯甲烷提取物能明显降低CCl4引起的AST,ALT增高.结论:茵陈三氯甲烷提取部位为其发挥保肝作用的有效部位.     

Antioxidant and hepatoprotective activities of low molecular weight sulfated polysaccharide from Laminaria japonica

A low molecular weight sulfated polysaccharide (LMWF) was prepared from Laminaria japonica by mild acid hydrolysis. The antioxidant activity of LMWF in vitro was studied using three kinds of oxygen free radical systems. LMWF had effective scavenging abilities on superoxide radical, hydroxyl radical and hypochlorous acid directly in vitro. The hepatoprotective effect of LMWF was studied using two acute liver injury mice models induced by carbon tetrachloride (CCl₄) and D-galactosamine (D-GalN). Addition of LMWF significantly lowered the content of serum malonaldehyde and markedly increased the activities of superoxide dismutase and glutathione peroxidase, compared with the model groups in both kinds of liver injury mice. Moreover, administration of LMWF significantly inhibited the elevation of glutamate pyruvate transaminase induced by CCl₄ and D-GalN in mice. The results suggest that the antioxidant activity of LMWF plays an important role in its hepatoprotective effect in the liver injury mice induced by CCl₄ and D-GalN.     

Evaluation of oxidative stress during apoptosis and necrosis caused by carbon tetrachloride in rat liver

After 12, 18, and 24 h of oral administration of carbon tetrachloride (as a 1:1 mixture with mineral oil: 4 ml/kg body weight) to rats, the activity of caspase-3-like protease in the liver increased significantly compared to that in the control group that was given mineral oil (4 ml/kg). In plasma, the activity of caspase-3 was barely detectable in the control rat, but increased significantly 24 h after drug administration along with a dramatic increase in glutamate oxaloacetate transaminase. These results indicate that carbon tetrachloride causes apoptosis in the liver by activating caspase-3, which is released to plasma by secondary necrosis. After 18 and 24 h of carbon tetrachloride administration, the liver concentration of hydrophilic vitamin C was decreased significantly, while that of hydrophobic vitamin E was not affected. The plasma concentration of vitamins C and E was not influenced significantly. These results suggest that carbon tetrachloride induces oxidative stress mainly in the aqueous phase of the liver cell.     

Hepatoprotective effect of Hibiscus hispidissimus Griffith, ethanolic extract in paracetamol and CCl4 induced hepatotoxicity in Wistar rats

Hibiscus hispidissimus Griff. is used in tribal medicine of Kerala, the southern most state of India, to treat liver diseases. In the present study, the effect of the ethanolic extract of Hibiscus hispidissimus whole plant on paracetamol (PCM)-induced and carbon tetrachloride (CCl4)-induced liver damage in healthy Wistar albino rats was studied. The results showed that significant hepatoprotective effects were obtained against liver damage induced by PCM and CCl4 as evidenced by decreased levels of serum enzymes, glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SAKP), serum bilirubin (SB) and an almost normal histological architecture of the liver of the treated groups compared to the toxin controls. The extract also showed significant antilipid peroxidant effects in vitro, besides exhibiting significant activity in quenching 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical, indicating its potent antioxidant effects.     

Hepatoprotective activity of Azadirachta indica leaves on paracetamol induced hepatic damage in rats.

Effect of A. indica leaf extract on serum enzyme levels (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, acid phosphatase and alkaline phosphatase) elevated by paracetamol in rats was studied with a view to observe any possible hepatoprotective effect of this plant. It was interesting to observe that serum enzyme levels were much elevated in paracetamol induced animals than in those receiving a combination of paracetamol and lead extract. It is stipulated that the extract treated group was protected from hepatic cell damage caused by paracetamol induction. The findings were further confirmed by histopathological study of liver.     

Hepatoprotective and antioxidant effects of Hibiscus sabdariffa extract against carbon tetrachloride-induced hepatocyte damage in Cyprinus carpio

The present study aims to evaluate the hepatoprotective and antioxidant effects of Hibiscus sabdariffa extract on the carbon tetrachloride (CCl(4))-induced hepatocyte damage in fish and provide evidence as to whether it can be potentially used as a medicine for liver diseases in aquaculture. H. sabdariffa extract (100, 200, and 400?μg/mL) was added to the carp primary hepatocyte culture before (pre-treatment), after (post-treatment), and both before and after (pre- and post-treatment) the incubation of the hepatocytes with CCl(4). CCl(4) at 8?mM in the culture medium produced significantly elevated levels of lactate dehydrogenase (LDH), glutamate oxalate transaminase (GOT), glutamate pyruvate transaminase (GPT), and malondialdehyde (MDA) and significantly reduced levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Pre-treatment and pre- and post-treatment of the hepatocytes with H. sabdariffa extract significantly reduced the elevated levels of LDH, GOT, GPT, and MDA and increased the reduced activities of SOD and GSH-Px in a dose-dependent manner; post-treatment did not show any protective effect. The results suggest that H. sabdariffa extract can be potentially used for preventing rather than curing liver diseases in fish.     

Hepatoprotective activity of Psidium guajava Linn. leaf extract

The study was designed to evaluate the hepatoprotective activity of P. guajava in acute experimental liver injury induced by carbon tetrachloride, paracetamol or thioacetamide and chronic liver damage induced by carbon tetrachloride. The effects observed were compared with a known hepatoprotective agent, silymarin. In the acute liver damage induced by different hepatotoxins, P. guajava leaf extracts (250 and 500mg/kg, po) significantly reduced the elevated serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin. The higher dose of the extract (500 mg/kg, po) prevented the increase in liver weight when compared to hepatoxin treated control, while the lower dose was ineffective except in the paracetamol induced liver damage. In the chronic liver injury induced by carbon tetrachloride, the higher dose (500 mg/kg, po) of P. guajava leaf extract was found to be more effective than the lower dose (250 mg/kg, po). Histological examination of the liver tissues supported the hepatoprotection. It is concluded that the aqueous extract of leaves of guava plant possesses good hepatoprotective activity.     

4-羟基苯并恶唑-2-酮对四氯化碳致小鼠急性肝损伤保护作用

日的研究4一羟基苯并恶唑-2-酮（4-hydroxy-2-benzoxazolone,HBOA）对四氯化碳所致小鼠急性肝损伤的保护作用,并探讨其疗效机制。方法采用腹腔注射四氯化碳（carbonte trachloride,cch）制备小鼠急性肝损伤模型,HBOA灌胃给药,检测小鼠血清中的乳酸脱氢酶（LDH）活性以及肝组织中过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）含量,并用免疫组化法观察肿瘤坏死因子（TNF-a）的表达情况。结果HBOA能明显降低CCh致急性肝损伤小鼠血清LDH活性,同时升高肝组织中CAT、GSH-Px的活性并降低肝组织中TNF-a的表达。结论HBOA对CCh所致小鼠急性肝损伤有一定的保护作用。     

Protective effects of cassia seed ethanol extract against carbon tetrachloride-induced liver injury in mice

Oxidative stress has been recognized as a critical pathogenetic mechanism for the initiation and the progression of hepatic injury in a variety of liver disorders. Antioxidants, including many natural compounds or extracts, have been used to cope with liver disorders. The present study was designed to investigate the hepatoprotective effects of cassia seed ethanol extract (CSE) in carbon tetrachloride (CCl(4))-induced liver injury in mice. The animals were pre-treated with different doses of CSE (0.5, 1.0, 2.0 g/kg body weight) or distilled water for 5 days, then were injected intraperitoneally with CCl(4) (0.1% in corn oil, v/v, 20 ml/kg body weight), and sacrificed at 16 hours after CCl(4) exposure. The serum aminotransferase activities, histopathological changes, hepatic and mitochondrial antioxidant indexes, and cytochrome P450 2E1 (CYP2E1) activities were examined. Consistent with previous studies, acute CCl(4) administration caused great lesion to the liver, shown by the elevation of the serum aminotransferase activities, mitochondria membrane permeability transition (MPT), and the ballooning degeneration of hepatocytes. However, these adverse effects were all significantly inhibited by CSE pretreatment. CCl(4)-induced decrease of the CYP2E1 activity was dose-dependently inhibited by CSE pretreatment. Furthermore, CSE dramatically decreased the hepatic and mitochondrial malondialdehyde (MDA) levels, increased the hepatic and mitochondrial glutathione (GSH) levels, and restored the activities of superoxide dismutase (SOD), glutathione reductase (GR), and glutathione S-transferase (GST). These results suggested that CSE could protect mice against CCl(4)-induced liver injury via enhancement of the antioxidant capacity.     

关龙胆地上部分的保肝作用

选用D-半乳糖胺、硫代乙酰胺、四氯化碳三个肝损伤毒物构建肝损伤模型,研究了关龙胆地上部分对于不同机制引起的肝损伤的保肝作用。实验结果表明关龙胆地上部分有保肝作用,可降低各种肝损伤模型的ALT(谷丙转氨酶)、AST(谷草转氨酶)、AKP(碱性磷酸酶)等,从而证明了关龙胆地上部分有一定药用价值,用全草取代地下部分入药有一定的可行性。     

The Chemokine CCL3 Promotes Experimental Liver Fibrosis in Mice

Liver fibrosis is associated with infiltrating immune cells and activation of hepatic stellate cells. We here aimed to investigate the effects of the CC chemokine CCL3, also known as macrophage inflammatory protein-1α, in two different fibrosis models. To this end, we treated mice either with carbon tetrachloride or with a methionine- and choline-deficient diet to induce fibrosis in CCL3 deficient and wild-type mice. The results show that the protein expression of CCL3 is increased in wild-type mice after chronic liver injury. Deletion of CCL3 exhibited reduced liver fibrosis compared to their wild-type counterparts. We could validate these results by treating the two mouse groups with either carbon tetrachloride or by feeding a methionine- and choline-deficient diet. In these models, lack of CCL3 is functionally associated with reduced stellate cell activation and liver immune cell infiltration. In vitro, we show that CCL3 leads to increased proliferation and migration of hepatic stellate cells. In conclusion, our results define the chemokine CCL3 as a mediator of experimental liver fibrosis. Thus, therapeutic modulation of CCL3 might be a promising target for chronic liver diseases.     

Sake yeast suppresses acute alcohol-induced liver injury in mice

Brewer's and baker's yeasts appear to have components that protect from liver injury. Whether sake yeast, Saccharomyces cerevisiae Kyokai no. 9, also has a hepatoprotective effect has not been examined. Here we show that sake yeast suppresses acute alcoholic liver injury in mice. Male C57BL/6 mice that had been fed a diet containing 1% sake yeast for two weeks received three doses of ethanol (5 g/kg BW). In the mice fed sake yeast, ethanol-induced increases in triglyceride (TG) and glutamate pyruvate transaminase (GPT) were significantly attenuated and hepatic steatosis was improved. In addition, sake yeast-fed mice showed a smaller decrease in hepatic S-adenosylmethionine (SAM) level and a smaller increase in plasma homocysteine (Hcy) level after ethanol treatment than the control mice, suggesting that a disorder of methionine metabolism in the liver caused by ethanol was relieved by sake yeast. These results indicate that sake yeast protects against alcoholic liver injury through maintenance of methionine metabolism in the liver.