Protective effect of Sida cordata leaf extract against CCl4 induced acute liver toxicity in rats

ObjectiveTo investigate the hepatoprotective potential of Sida cordata (Malvaceae) (S. cordata) in experimental rats to validate its traditional claim.MethodsWister albino rats were divided into 6 groups: Group I served as control; Group II served as hepatotoxic (CCl₄ treated) group; Group III, IV and V served as (100, 200 and 400 mg/kg b.w.) S. cordata leaf extract (SCLE) treated groups; Group VI served as positive control (Silymarin) treated group. Liver marker enzymes serum glutamate oxyloacetic transaminase, serum glutamic pyruvic transaminase, pancreatic enzymatic antioxidants superoxide dismutase (SOD), lipid peroxidation, catalase (CAT), reduced glutathione (GSH) were measured and compared along with histopathological studies.ResultsObtained results show that the treatment with SCLE significantly (P<0.05-<0.001) and dose-dependently reduced CCl₄ induced elevated serum level of hepatic enzymes. Furthermore, SCLE significantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels, which was confirmed by the histopathological studies.ConclusionsThe results of this study strongly indicate the protective effect of SCLE against CCl₄ induced acute liver toxicity in rats and thereby scientifically support its traditional use.     

Nephroprotective activity of Solanum xanthocarpum fruit extract against gentamicin-induced nephrotoxicity and renal dysfunction in experimental rodents

ObjectiveTo evaluate nephroprotective potential of Solanum xanthocarpum (S. xanthocarpum) fruit extract(SXE) against gentamicin (GM) induced nephrotoxicity and renal dysfunction.MethodsTwenty-four Wistar rats were divided into four groups (n=6). Control rats that received normal saline (i.p.) and 0.5% carboxymethyl cellulose (p.o.) per day for 8 d. Nephrotoxicity was induced in rats by intraperitoneal administration of GM (100 mg/kg/d for 8 d) and were treated with SXE (200 and 400 mg/kg/d (p.o.) for 8 d). Plasma and urine urea and creatinine, kidney weight, urine output, blood urea nitrogen, renal enzymatic and non-enzymatic antioxidants and lipid peroxidation was evaluated along with histopathological investigation in various experimental groupsof rats.ResultsIt was observed that the GM treatment induced significant elevation (P<0.001) in plasma and urine urea, creatinine, kidney weight, blood urea nitrogen, renal lipid peroxidation along with significant decrement (P<0.001) in urine output, renal enzymatic and non-enzymatic antioxidants. SXE 200 and 400 mg/kg treatment to GM treated rats recorded significant decrement (up to P<0.001) in plasma and urine urea and creatinine, renal lipid peroxidation along with significant increment (up to P<0.001) in renal enzymatic and non-enzymatic antioxidants. Histological observations of kidney tissues too correlated with the biochemical observations.ConclusionsThese finding powerfully supports that S. xanthocarpum fruit extract acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GM both in the biochemical and histopathological parameters and thus validates its ethnomedicinal use.     

Hepatoprotective potential of petroleum ether leaf extract of Crossandra infundibuliformis on CCl4 induced liver toxicity in albino mice

ObjectiveTo analyze the hepatoprotective effect of the Crossandra infundibuliformis.MethodsHepatotoxicity was induced by carbon tetrachloride. Petroleum ether extract of dried leaves was administrated to mice for 7 days. The hepatoprotective effect of petroleum ether extract was evaluated by the assay of liver function biochemical parameters.ResultsThe result clearly indicates that petroleum ether extract showed significant hepatoprotection when compared with standard Silumarin.ConclusionsThe petroleum ether extract of the leaves of Crossandra infundibuliformis possess significant acute hepatoprotective activity. Thus further investigation on this species would bring a promising drug for liver disorders.     

Hepatoprotective activity of Spillanthes acmella Extracts against CCl4-induced liver toxicity in rats

ObjectiveHepato protective activity of Spillanthes acmella Extracts (70% ethanol, methanol, ethyl acetate and hexane) were investigated.MethodsHepatoprotective activity was assessed against CCl4 induced liver intoxication.ResultsThe extracts were produced concentration dependent percentage protection in the reduction of enzymes (Serum Glutamate Oxaloacetate Transaminase, Serum Glutamate Pyruvate Transaminase, Alkaline phasphatase and Total bilirubin) levels against CCl4 induced liver intoxication in rats. Among all extracts methanol extract showed better activity compare to other extracts with percentage protection of SGOT (84.39%), SGPT (79.04%), ALP (78.15%) and Total bilirubin (80.00%) levels at a dose of 500mg/kg.ConclusionsFrom the results obtained during the present study it could be concluded that Spillanthes acmella extracts has components that have hepato protective effects.     

Hepatoprotective effects of baicalein against CCl4-induced acute liver injury in mice

AIM: To investigate the hepatoprotective effect of baicalein against carbon tetrachloride (CCl₄)-induced liver damage in mice.METHODS: Mice were orally administered with baicalein after CCl₄ injection, and therapeutic baicalein was given twice a day for 4 d. The anti-inflammation effects of baicalein were assessed directly by hepatic histology and serum alanine aminotranferease and aspartate aminotransferase measurement. Proliferating cell nuclear antigen was used to evaluate the effect of baicalein in promoting hepatocyte proliferation. Serum interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) levels were measured by enzyme-linked immunosorbent assay and liver IL-6, TNF-α, transforming growth factor-α (TGF-α), hepatocyte growth factor (HGF) and epidermal growth factor (EGF) genes expression were determined by quantitative real-time polymerase chain reaction.RESULTS: CCl₄-induced acute liver failure model offers a survival benefit in baicalein-treated mice. The data indicated that the mRNA levels of IL-6 and TNF-α significantly increased within 12 h after CCl₄ treatment in baicalein administration groups, but at 24, 48 and 72 h, the expression of IL-6 and TNF-α was kept at lower levels compared with the control. The expression of TGF-α, HGF and EGF was enhanced dramatically in baicalein administration group at 12, 24, 48 and 72 h. Furthermore, we found that baicalein significantly elevated the serum level of TNF-α and IL-6 at the early phase, which indicated that baicalein could facilitate the initiating events in liver regeneration.CONCLUSION: Baicalein may be a therapeutic candidate for acute liver injury. Baicalein accelerates liver regeneration by regulating TNF-α and IL-6 mediated pathways.     

Hepatoprotective and antioxidant activity of methanolic extract of flowers of Nerium oleander against CCl4-induced liver injury in rats

ObjectiveTo investigate the antioxidant and hepatoprotective activity of methanolic flower extract of Nerium oleander against CCl₄-induced hepatotoxicity in rats.MethodsIn vitro antioxidant activity of methanolic extract of flowers of Nerium oleander (MENO–F) was evaluated by various assays, including reducing power, lipid peroxidation, DPPH, ABTS, superoxide anion, hydroxyl radicals and metal chelation. The hepatoprotective and in vivo antioxidant activity of MENO-F were evaluated against CCl₄–induced hepatic damage in rats. The MENO-F at dose of 100, 200 and 400 mg/kg were administered orally once daily for seven days. Serum enzymatic levels of serum glutamate oxaloacetate transaminase (AST), serum glutamate pyruvate transaminase (ALT), serum alkaline phosphatase (ALP) and total bilirubin were estimated along with estimation of superoxide dismutase (SOD) and malondialdehyde (MDA) levels in liver tissues. Further histopathological examination of the liver sections was carried out to support the induction of hepatotoxicity and hepatoprotective efficacy.ResultsThe extract showed potent activities on reducing power, lipid peroxide, DPPH, ABTS, superoxide anion, hydroxyl radical and metal chelation. The substantially elevated serum enzymatic levels of AST, ALT, ALP and total bilirubin were found to be restored towards normalization significantly by the MENO-F in a dose dependent manner with maximum hepatoprotection at 400 mg/kg dose level. The histopathological observations supported the biochemical evidences of hepatoprotection. Elevated level of SOD and decreased level of MDA further strengthen the hepatoprotective observations.ConclusionsThe results of the present study strongly reveal that MENO-F has potent antioxidant activity and hepatoprotective activity against CCl₄-induced hepatic damage in experimental animals.     

Hepatoprotective effect of manual acupuncture at acupoint GB34 against CCl4-induced chronic liver damage in rats

AIM: To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan (GB34) on CCl4-induced chronic liver damage in rats. METHODS: Rats were injected intraperitoneally with CC4l (1 mL/kg) and treated with manual acupuncture using reinforcing manipulation techniques at left GB34 (Yanglingquan) 3 times a week for 10 wk. A non-acupoint in left gluteal area was selected as a sham point. To estimate the hepatoprotective effect of manual acupuncture at GB34, measurement of liver index, biochemical assays including serum ALT, AST, ALP and total cholesterol, histological analysis and blood cell counts were conducted. RESULTS: Manual acupuncture at GB34 reduced the liver index, serum ALT, AST, ALP and total cholesterol levels as compared with the control group and the sham acupuncture group. It also increased and normalized the populations of WBC and lymphocytes. CONCLUSION: Manual acupuncture with reinforcing manipulation techniques at left GB34 reduces liver toxicity, protects liver function and liver tissue, and normalizes immune activity in CCl4-intoxicated rats.     

Hepatoprotective effect of Geranium schiedeanum against ethanol toxicity during liver regeneration

AIM: To evaluate the effect of an extract of Geranium schiedeanum(Gs) as a hepatoprotective agent against ethanol(Et OH)-induced toxicity in rats. METHODS: Male Wistar rats weighing 200-230 g were subjected to a 70% partial hepatectomy(PH); they were then divided into three groups(groups 1-3). During the experiment, animals in group 1 drank only water. The other two groups(2-3) drank an aqueous solution of Et OH(40%, v/v). Additionally, rats in group 3 received a Gs extract daily at a dose of 300 mg/kg body weight intragastically. Subsequently, to identify markers of liver damage in serum, alanine aminotransferase, aspartate aminotransferase, albumin and bilirubin were measured by colorimetric methods. Glucose, triglyceride and cholesterol concentrations were also determined. In addition, oxidative damage was estimated by measuring lipid peroxidation [using thiobarbituric-acid reactive substances(TBARS)] in both plasma and the liver and by measuring the total concentration of antioxidants in serum and the total antioxidant capacity in the liver. In addition, a liver mass gain assessment, total DNA analysis and a morpho-histological analysis of the liver from animals in all three groups were performed and compared. Finally, the number of deaths observed in the three groups was analyzed.RESULTS: Administration of the Geranium shiedeanum extract significantly reduced the unfavorable effect of ethanol on liver regeneration(restitution liver mass: PHEt OH group 60.68% vs PH-Gs-Et OH group 69.22%). This finding was congruent with the reduced levels of hepatic enzymes and the sustained or increased levels of albumin and decreased bilirubin in serum. The extract also modified the metabolic processes that regulate glucose and lipid levels, as observed from the serum measurements. Lower antioxidant levels and the liver damage induced by Et OH administration appeared to be mitigated by the extract, as observed from the TBARs(PH-Et OH group 200.14 mmol/mg vs PH-Gs-Et OH group 54.20 mmol/mg; P 0.05), total status of antioxidants(PH-Et OH group 1.43 mmol/L vs PH-Gs-Et OH group 1.99 mmol/L; P 0.05), total antioxidant capacity values, liver mass gain and total DNA determination(PH-Et OH group 4.80 mg/g vs PH-Gs-Et OH 9.10 mg/g; P 0.05). Overall, these processes could be related to decreased mortality in these treated animals.CONCLUSION: The administered extract showed a hepatoprotective effect, limiting the Et OH-induced hepatotoxic effects. This effect can be related tomodulating oxido-reduction processes.     

Hepatoprotective effect of Averrhoea carambola fruit extract on carbon tetrachloride induced hepatotoxicity in mice

ObjectiveTo investigate the hepatoprotective activity of Averroha carambola fruit extract against carbon tetrachloride induced hepatic injury.MethodsHepatotoxicity was induced on albino mice by intraperitoneal administration of CCl₄, half an hour after the administration of the last dose of the extract of Averroha carambola fruit. Aqueous extract of the fruit of Averroha carambola was administered at a dose of 0.9 g/kg body weight once daily for seven days. The hepatic injury and its prevention was assessed by the estimation of serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphates (ALP), glutathione level and histopathological studies of liver.ResultsPre-treatment of mice with the fruit extract of Averrhoea carambola significantly reduced serum levels of ALT, AST and ALP enzyme and significantly increased the liver reduced glutathione levels 24 h after the administration of carbon tetrachloride. A marked improvement in the enzyme activities and the liver reduced glutathione level was observed in the pre-treated mice 4 days after the administration of carbon tetrachloride. Histopathological studies provided supportive evidence for the biochemical analysis.ConclusionsThe aqueous extract of the fruit of Averrhoea carambola has hepatoprotective effect against carbon tetrachloride induced liver damage in mice.     

Hepatoprotective activity of brown alga Padina boergesenii against CCl4 induced oxidative damage in Wistar rats

ObjectiveTo investigate the protective effects of brown alga Padina boergesenii (P. boergeseii) against carbon tetrachloride (CCl 4) induced oxidative damage and liver fibrosis in rats.MethodsTo assess the hepatic damage liver weight, the activities of TBARS level, glutathione, SOD, CAT and GP x in circulation and liver.ResultsThe group of rats induced with CCl 4 alone (2 mL/kg body weight), showed noticeable increase in the liver weight and TBARS level. Followed by, the level of antioxidant enzymes glutathione peroxidase, Superoxide dismutase and catalase was also significantly (P <0.01) diminished. Where as, the rats pretreated with P. boergesenii (150 mg/kg body weight) modulated the CCl 4 induced liver fibrosis. The level of antioxidant enzymes and lipid peroxidation products was found to be significantly (P <0.01) attenuated to near normal level, when compared with rats induced with CCl 4 alone. In order to assess the role of carotenoids in the relevant activity, total carotenoid content of the extract was analysed and found to be 0.59 mg / g fresh weight (FW). Further, the histopathogical studies provide a supportive evidence for this study to show the protective nature of P. boergesenii.ConclusionsThe protective role of brown alga P. boergesenii extract has confirmed its potential activity through its antioxidant sparing actions against CCl 4 i nduced free radical damage. However, the possible mechanism of hepatoprotection is rather speculative at this stage and investigations are underway to isolate and characterize the bioactive compounds from P. boergesenii.     

黄果茄植物提取物的灭螺效果及对鱼类和大鼠急性毒性试验研究

目的 掌握和了解黄果茄植物提取物（SX）对钉螺的杀灭效果和对鱼类以及大鼠的急性毒性作用。方法 进行了常规的灭螺试验和鱼类急性毒性试验以及大鼠急性经口毒性试验。结果 SX浓度为4．32mg/L时浸泡湖北钉螺,24h死亡率为96．7％,48h死亡率达100％;SX对鱼类稀有Ju鲫的急性毒性试验,在0．27mg/L浓度中,24h的死亡率为0,在17＝28mg/L浓度中,24h死亡率为100％;SX对稀有Ju鲫的LC50为2．02mg/L,95%的可信限为1．33－3．06mg/L。对大鼠急性经口毒性的绝对致死剂量为2150mg/kg体重,LD50为794mg/kg体重,95％可信限为584－1080mg/kg体重。结论 SX具有较好的灭螺效果,但对鱼类稀有Ju鲫有中等毒性作用,对大鼠的作用属低毒类。     

Hepatoprotective effect of Woodfordia fruticosa Kurz flowers on diclofenac sodium induced liver toxicity in rats

ObjectiveTo evaluate the protective effect of Woodfordia fruticosa Kurz flowers against experimentally induced liver toxicity in rats.MethodsTwo different doses of methanol extract of Woodfordia fruticosa (WFM) were evaluated for the hepatoprotective activity against diclofenac sodium induced hepatotoxicity in rats. Various biochemical parameters like alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), blood urea nitrogen (BUN) from serum; total protein (TP), glutathione (GSH) levels, catalase (CAT) and glutathione peroxidase (GPx) activities from liver were studied; histopathologic changes of liver were also evaluated.ResultsWFM effectively reduced the elevated levels of serum ALT, AST, ALP and BUN, enhanced the reduced TP, ALB and hepatic GSH, CAT, GPx activity. The histopathological analysis suggested that WFM decreased the degree of liver fibrosis induced by diclofenac.ConclusionsThis study demonstrates the hepatoprotective activity of WFM and thus scientifically support the use of this plant in traditional medicine for the treatment of liver disorders.     

姜黄素对CCl4所致急性肝损伤大鼠的保护作用及其机制研究*

目的 观察姜黄素对四氯化碳（CCl₄）所致急性肝损伤大鼠的保护作用,并研究其作用机制。方法 将60只SD大鼠随机分为对照组、模型组、水飞蓟素组（100 mg.kg^-1）和大、中、小剂量姜黄素组（100、50和25 mg.kg^-1）,每组10只。建模成功后隔日给药灌胃,共30 d。取下腔静脉血和肝组织,分别检测血清乳酸脱氢酶（LDH）和前列腺素E2（PGE2）水平,采用Bio-Rad公司试剂盒检测肝组织匀浆白介素-6（IL-6）、肿瘤坏死因子α（TNF-α）和环氧合酶-2（COX-2）水平。结果 对照组大鼠肝小叶结构完整清晰,肝细胞无坏死及脂肪变性,模型组肝组织损伤明显,经姜黄素处理肝组织炎性细胞浸润减少,肝组织损伤有不同程度的减轻;模型组大鼠血清LDH水平为（6458.00±423.72）IU/L,PEG2水平为（130.02±4.30）pg/ml,显著高于对照组[（1375.00±67.45） IU/L和（51.27±0.86）pg/ml,P<0.001],而各剂量姜黄素处理组和水飞蓟素组均可显著降低大鼠血清LDH和PGE2 水平（P<0.05）; 模型组大鼠肝组织匀浆IL-6、TNF-α和COX-2水平显著高于对照组（P<0.05）,而大中小剂量姜黄素处理组和水飞蓟素处理组肝组织IL-6、TNF-α和COX-2水平显著低于模型组（P<0.05）。结论 姜黄素对CCl4所致大鼠急性肝损伤具有保护作用,其机制可能是抑制了IL-6、TNF-α、COX-2和PGE2等炎性细胞因子的释放。     

Hepatoprotective activity of Mentha arvensis Linn. leaves against CCL4 induced liver damage in rats

ObjectiveTo study the Hepatoprotective activity of ethanol, chloroform and aqueous extracts of Mentha arvensis leaves against CCL₄ induced liver damage in rats.MethodsHepatotoxicity was induced by CCL₄ and the biochemical parameters such as serum glutamate pyruvate transminase (sGPT), serum glutamate oxaloacetate transaminase (sGOT), alkaline phosphatase (sALP), serum bilirubin (sB) and histopathological changes in liver were studied along with silymarin as standard Hepatoprotective agents.ResultsThe Phytochemical investigation of the extracts showed presence of flavonoids, steroids, triterpenoids, alkaloids, glycosides, carbohydrates, tannins, phenolic compounds. Treatment of the rats with chloroform, ethanol and aqueous extract with CCL₄ administration caused a significant reduction in the values of sGOT, sGPT, sALP and sB (P < 0.01) almost comparable to the silymarin. The Hepatoprotective was confirmed by histopathological examination of the liver tissue of control and treated animals.ConclusionsFrom the results it can be concluded that Mentha arvensis possesses Hepatoprotective effect against CCL₄ induced liver damage in rats.     

Metabolomics of Fuzi-Gancao in CCl4 induced acute liver injury and its regulatory effect on bile acid profile in rats

BACKGROUND Fuzi (Radix aconiti lateralis)-Gancao (Radix glycyrrhizae) is one of the most classical drug pairs of traditional Chinese medicine. In clinical practice, decoctions containing Fuzi-Gancao (F-G) are often used in the treatment of liver diseases such as hepatitis and liver failure.AIMTo investigate the metabolomics of F-G in CCl₄ induced acute liver injury in rats and its regulatory effect on the bile acid profile.METHODSThe pharmacodynamic effect of F-G on CCl₄ induced acute liver injury in rats was evaluated, and an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of 92 metabolites from multiple pathways was established to explore the protective metabolic mechanism of F-G in serum on the liver.RESULTSTwenty-four differential metabolites were identified in serum samples. The primary bile acid biosynthetic metabolic pathway was the major common pathway in the model group and F-G group. Subsequently, a UPLC-MS/MS method for simultaneous determination of 11 bile acids, including cholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, glycocholic acid, chenodeoxycholic acid, deoxycholic acid, taurochenodeoxycholic acid, taurocholic acid, and glycinic acid, was established to analyze the regulatory mechanism of F-G in serum. F-G decreased the contents of these 11 bile acids in serum in a dose-dependent manner compared with those in the model control group.CONCLUSIONF-G could protect hepatocytes by promoting the binding of free bile acids to glycine and taurine, and reducing the accumulation of free bile acids in the liver. F-G could also regulate the compensatory degree of taurine, decreasing the content of taurine-conjugated bile acids to protect hepatocytes.     

Ginkgo biloba extract alleviates liver fibrosis induced by CCl in rats.

AIMS: To investigate the protective effect of Ginkgo biloba extract (GbE) on liver fibrosis induced by carbon tetrachloride (CCl4) in rats and expressions of transforming growth factor beta1 (TGF-beta1) and collagen I during this period. METHODS: The effect of GbE on liver fibrogenesis was detected by hematoxylin and eosin staining (H&E staining), Masson's trichrome staining, and electron microscope study. Blood samples were collected for measurement of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin. Malondialdehyde (MDA) in liver tissue was detected by the thiobarbituric acid (TBA) method. Immunohistochemistry assay and RT-PCR were used to examine the protein expressions and mRNA levels of TGF-beta1 and collagen I, respectively. RESULTS: H&E, Masson's trichrome stainings and electron microscope study showed liver fibrosis in rats was greatly alleviated when treated with GbE. Additionally, there was a remarkable improvement of serum ALT, AST, albumin and MDA in the GbE-treated group. Immunohistochemistry and RT-PCR results showed GbE intervention significantly inhibited TGF-beta1 and collagen I expressions in rat liver. No side effects of GbE were found during these experiments. But GbE could not reverse the pathological changes of liver fibrosis completely when compared with normal control. CONCLUSION: GbE can partially protect rat liver from the fibrogenesis induced by CCl4. The mechanism may lie in its effect of inhibiting oxidative stress caused by liver injury and expressions of signal molecules such as TGF-beta1. GbE may thus be of potential help as a medicament or food additive for alleviation of liver fibrogenesis.     

Ginkgo biloba extract reverses CCl4-induced liver fibrosis in rats

AIM: To study the reversing effect of Ginkgo biloba extract (GbE) on established liver fibrosis in rats. METHODS: Following confirmation of CCI4-induced liver fibrosis, GbE or saline was administrated to the rats for 4 weeks. The remaining rats received neither CCI 4 norGbE as normal control. The four groups were compared in terms of serum enzymes, tissue damage, expression of αSMA and tissue inhibitor-1 of metalloproteinase (TIMP-1) and metalloproteinase-1 (MMP-1). RESULTS: Compared with saline-treated group, liver fibrosis rats treated with GbE had decreased serum total bilirubin (P&lt;0.01) and aminotransferase levels (P&lt;0.01) and increased levels of serum albumin (P&lt;0.01). Microscopic studies revealed that the livers of rats receiving GbE showed allieviation in fibrosis (P&lt;0.05) as well as expression of αSMA (P&lt;0.01). The liver collagen and reticulum contents were lower in rats treated with GbE than saline-treated group (P&lt;0.01). RT-PCR revealed that the level of TIMP-1 decreased while the level of MMP-1 increased in GbE group. CONCLUSION: Administration of GbE improved CCI4-induced liver fibrosis. It is possibly attributed to its effect of inhibiting the expression of TIMP-1 and promoting the apoptosis of hepatic stellate cells.     

内质网应激在四氯化碳致大鼠急性肝损伤中的作用探讨

目的研究内质网应激在四氯化碳诱导的大鼠急性肝损伤中的变化规律和作用机制。方法采用四氯化碳制备大鼠急性肝损伤模型，动态测定大鼠肝脏GRP78蛋白和caspase 12酶原表达情况，测定大鼠血清ALT、AST水平、肝组织SOD活性、MDA浓度和caspase 3活性变化；采用HE染色和TUNEL法观察肝组织病理形态学和肝细胞凋亡变化。结果四氯化碳染毒后大鼠肝脏GRP78蛋白表达显著增加，caspase 12酶原表达相应减少，呈一定时间依赖方式。大鼠染毒后出现血清ALT、AST水平以及组织MDA含量显著升高，SOD活性明显下降，与对照组有显著性差异（P〈0．01）；染毒后大鼠肝组织caspase 3活性亦显著升高，病理学及TUNEL法检测结果均显示肝脏有严重损伤，大量肝细胞发生凋亡。结论四氯化碳诱导大鼠肝损伤时GRP78和caspase 12的表达变化表明发生了内质网应激反应，其变化趋势和大鼠肝细胞凋亡、病理损伤一致，这一结果提示内质网应激介导的肝细胞凋亡参与了大鼠肝损伤。     

Hepatoprotective effect of Premna corymbosa (Burm. f.) Rottl. & Willd. leaves extract on CCl4 induced hepatic damage in Wistar albino rats

ObjectiveTo investigate the hepetoprotective activity of Premna corymbosa leaves against carbon tetrachloride (CCl₄) induced hepatic damage.MethodsHepatotoxicity was induced in wistar rats of both sexes by intraperitoneal injection of CCl₄, 1 mL/kg body weight for every 72 h. The ethanolic extract of Premna corymbosa leaves were administrated at doses of 200 & 400 mL/kg body weight, p. o., daily for 14 days. The hepatotoxicity and its prevention was assessed by serum markers like serum alkaline phosphatase (SALP), serum triglycerides (STG), serum total protein (STP), serum cholesterol (SC), and liver wet weight and histopathological studies of the liver.ResultsIn treatment with the ethanolic extract, the toxic effect of CCl₄ was controlled significantly (P < 0.01) by restoration of the levels of biochemical parameters as compared to normal and standard drug silymarin treated groups. The liver weight was reduced by the ethanolic extract treated groups. The histopathology of the liver sections evidenced the hepatoprotective activity.ConclusionThe ethanolic extract of the leaves of Premna corymbosa possess significant acute hepatoprotective activity. Premna corymbosa can be recommended for the liver disorders.