Protective effect of some tropical vegetables against CCl4-induced hepatic damage

In the present study, ethanolic extracts of some tropical vegetables were investigated for their hepatoprotective effect against CCl4-induced liver damage in rats. CCl4 at a dose of 0.5 mL/kg of body weight produced liver damage in rats as manifested by the rise in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total protein in serum (40.60 +/- 3.50 IU/L, 80.60 +/- 5.10 IU/L, and 73.20 +/- 1.87 g/L, respectively) and in liver homogenate (1,300.00 +/- 7.38 IU/L, 1,660.00 +/- 13.69 IU/L, and 250.00 +/- 7.51 g/L, respectively) compared to the control. The extracts at doses of 250 and 500 mg/kg of body weight were administered to the CCl4-treated rats. The vegetables at a dose of 250 mg/kg of body weight produced a significant hepatoprotective effect by decreasing the serum levels of ALT, AST, and total protein to values in the range of 11.21 +/- 1.90-16.22 +/- 1.00 IU/L, 29.00 +/- 2.70-48.00 +/- 2.10 IU/L, and 62.10 +/- 2.40-70.13 +/- 2.00 g/L and at a dose of 500 mg/kg of body weight to 13.00 +/- 1.20-21.00 +/- 1.30 IU/L, 40.00 +/- 2.5-59.00 +/- 2.20 IU/L, and 68.00 +/- 2.40-72.00 +/- 2.10 g/L, respectively. Similar results were obtained for liver homogenate levels of ALT, AST, and total protein with decreasing values compared with the CCl4-treated rats: 900.00 +/- 3.05-1,020.00 +/- 4.25 IU/L, 1,150.00 +/- 5.57-1,530.00 +/- 4.99 IU/L, and 150.00 +/- 3.12-185.00 +/- 3.00 g/L and 900.00 +/- 3.05-1,030.00 +/- 8.80 IU/L, 1,400.00 +/- 6.95-1,530.00 +/- 8.50 IU/L, and 165.0 +/- 5.50-210.00 +/- 4.41 g/L, respectively, at doses of 250 and 500 mg/kg of body weight, respectively. Furthermore, the effect of the extracts on lipid peroxidation, measured as malondialdehyde (MDA), was estimated on the liver homogenate. A significant hepatoprotective effect was also noticed with a decreased value of the MDA levels: 46.00 +/- 0.08-52.00 +/- 0.06 and 47.00 +/- 0.07-60.00 +/- 0.10 nmol of thiobarbituric acid-reactive substances/g of liver protein at doses of 250 and 500 mg/kg of body weight, respectively. It could be concluded that all the evaluated vegetables exhibit good hepatoprotective activities, though to varying degrees.     

Protective effect of Aronia melanocarpa fruit juice pretreatment in a model of carbon tetrachloride-induced hepatotoxicity in rats

The main active ingredients of Aronia melanocarpa fruit juice (AMFJ) are phenolic substances, mainly flavonoids from the anthocyanin subclass. AIM: The aim of the present study was to investigate the effect of AMFJ applied as pretreatment in a model of carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. MATERIAL AND METHODS: AMFJ was given orally to rats for 2 days at doses of 5, 10 and 20 ml/kg either alone or as pretreatment before the oral application of CCl4 (0.2 ml/kg, 2 days). The plasma activities of aspartate transaminase (AST) and alanine transaminase (ALT) were measured as markers of the liver cell damage. The levels of malondialdehyde (MDA), a lipid peroxidation marker, were determined in rat liver and plasma. RESULTS: Administration of CCl4 caused an elevation of plasma AST and ALT activities. It also induced an elevation of MDA levels in rat liver and plasma. AMFJ applied alone in the tested doses did not cause any significant changes in the measured enzyme activities and in MDA levels. AMFJ applied as pretreatment prevented the CCl4-induced increase of AST and ALT activities, and also prevented the elevation of plasma and liver MDA levels. CONCLUSIONS: AMFJ showed a protective effect in a model of CCl4-induced hepatotoxicity in rats. This effect might be due to the antioxidant activity of its active ingredients.     

Hepatoprotective effects of Artemisiae Capillaris Herba and Picrorrhiza Rhizoma combinations on carbon tetrachloride–induced subacute liver damage in rats

The hepatoprotective properties of Artemisiae Capillaris Herba (AC) and Picrorrhiza Rhizoma (PR) are well known. The aim of this study was to determine the optimal composition of AC and PR mixtures for better complimentary or alternative regimens in reducing the level of hepatic fibrosis. Ten weeks of carbon tetrachloride injections caused subacute hepatic damage, manifested as significantly less body weight gain and hepatic protein content, and a higher liver weight, serum aspartate aminotransferase and alanine aminotransferase levels, hepatic malondialdehyde (an index for lipid peroxidation), and hydroxyproline (an index for collagen synthesis) concentrations. The carbon tetrachloride–induced toxic effects were inhibited by 11 different AC/PR mixtures as well as the single AC or PR treatment. More favorable effects were detected in all mixed-formulation groups compared with the AC or PR single formulations. Moreover, the AC/PR 2:1 formulation showed the most favorable hepatoprotective activity. The AC and PR mixtures showed good synergic hepatoprotective activity that was attributed to increasing free-radical scavenging ability. Among the 11 types of mixed formula tested in this study, the AC/PR 2:1 formulation had the most impressive synergic effects on inhibiting the subacute hepatic damage induced by carbon tetrachloride in rats and showed more favorable effects than with an equal dose of silymarin.     

复方叶下珠对小鼠实验性肝损伤作用的研究

目的 研究复方叶下珠对小鼠实验性肝损伤的作用及其有关机制。方法 对采用四氯化碳(CCl4)所致的小鼠急、慢性肝损伤模型进行研究，检测小鼠血清中的丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、超氧化物歧化酶(SOD)、丙二醛(MDA)、总蛋白(TP)、白蛋白(ALB)及肝组织中的羟辅氨酸(Hyp)含量；并设联苯双酯(BPD)和秋水仙碱分别为急、慢性肝损伤实验的对照药。结果 复方叶下珠可显著地降低血清中的ALT，AST，MDA含量及肝组织中的Hyp水平，并可提高TP，ALB和SOD含量。结论 复方叶下珠对CCl4所致的急、慢性肝损伤有防治作用，其机制可能与清除自由基、抑制胶原蛋白的形成、促进蛋白合成等有关。     

Protection against carbon tetrachloride-induced hepatotoxicity by pretreating rats with the hemisuccinate esters of tocopherol and cholesterol.

Previous studies have demonstrated that alpha-tocopheryl hemisuccinate (TS) protects hepatocyte suspensions from chemical-induced toxicity. It has been suggested that TS cytoprotection is related to unique properties of the TS molecule or is dependent on the cellular release and activity of unesterified alpha-tocopherol (T). To test the unique cytoprotective nature of TS in vivo, the protective ability of T and tocopherol esters against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats was examined. Hepatoprotection [determined by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and histopathology] was not observed after T (or tocopheryl acetate and tocopheryl nicotinate) administration, even though this treatment resulted in a fivefold elevation in hepatic T content. Only pretreatment with TS (100 mg/kg, intraperitoneally) resulted in partial hepatoprotection against CCl4 (2.9 g/kg, orally) toxicity. These findings suggest that hepatoprotection results not from the cellular accumulation of T but rather from the intact TS molecule. To test this hypothesis, the hepatoprotective capacity of cholesteryl hemisuccinate (CS), unesterified cholesterol, and cholesteryl acetate (CA) was examined against CCl4 toxicity. As observed with the tocopherol derivatives, pretreatment with unesterified cholesterol or CA demonstrated no protective ability. However, when rats were pretreated with CS (100 mg/kg), the hepatotoxic effects of CCl4 (elevated serum AST and ALT levels and centrilobular necrosis) were completely prevented. The prevention of CCl4-induced hepatotoxicity by CS and TS do not appear to result from an alteration in hepatic drug metabolism. These data clearly demonstrate that CS and TS are unique and powerful cytoprotective agents against CCl4 hepatotoxicity in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)     

沙棘籽油对四氯化碳肝损伤的保护作用研究

目的研究沙棘籽油对四氯化碳(CCl4)引起的大鼠化学性肝损伤的保护作用,探讨其对CCl4肝损伤起保护作用的有效剂量。方法实验用健康雄性成年SD大鼠(180~220 g)72只,随机分为空白对照组、溶剂对照组、CCl4模型对照组和3个沙棘籽油实验组(0.167,0.333和0.500 g/kg体重)。沙棘籽油以食用花生油稀释至所需浓度,灌胃给予动物(2 ml/kg体重),空白对照组给予等体积蒸馏水灌胃,溶剂和模型对照组给予等体积花生油灌胃。于实验第45天将各组动物隔夜禁食16 h,模型组及受试样品组一次灌胃给予CCl4(200 mg/kg体重),24 h后处死动物,股动脉取血分离血清,测定血清ALT、AST水平,并取肝脏进行病理组织学检测。结果与CCl4模型对照组相比,沙棘籽油各剂量组大鼠血清ALT、AST均明显降低[(2 419±1 335),(2 832±1 074),(2 424±955),(4 396±3 026),(4 579±990),(5 106±1 479),(4 503±782),(21 861±14 291)nmol.s-1/L](P0.05);病理组织学检查结果显示,沙棘籽油高剂量组(0.500 g/kg体重)大鼠肝细胞水样变性和坏死程度以及总病变计分明显减轻(136.0±47.0vs288.0±70.0,P0.05),而中、低剂量组差异无统计学意义。结论沙棘籽油对CCl4造成的肝损伤具有明显保护作用,本实验中得出的有效剂量为0.500 g/kg体重。     

Curcumin or saikosaponin a improves hepatic antioxidant capacity and protects against CCl4-induced liver injury in rats

Curcumin and saikosaponin a, the bioactive phytochemicals of turmeric and Bupleurum, act as antioxidants. This study investigated the effects of supplementation with curcumin and/or saikosaponin a on hepatic lipids and antioxidant status in rats with CCl(4)-induced liver injury. Male Sprague-Dawley rats were randomly divided into control, CCl(4), CCl(4) + curcumin (0.005%; CU), CCl(4) + saikosaponin a (0.004%; SS), and CCl(4) + curcumin + saikosaponin a (0.005% + 0.004%; CU+SS) groups. CCl(4) (40% in olive oil) was injected intraperitoneally at a dose of 0.75 mL/kg once a week. Curcumin and/or saikosaponin a was administered orally 1 week before CCl(4) injection for 8 weeks. The pathological results showed that liver fibrosis was ameliorated in the SS and CU+SS groups. After 8 weeks, supplementation with curcumin and/or saikosaponin a significantly decreased plasma alanine aminotransferase and aspartate aminotransferase activities, as well as plasma and hepatic cholesterol and triglyceride levels. The CU+SS group showed reversal of the impaired hepatic superoxide dismutase activity and an increase in total glutathione level. Supplementation with curcumin and/or saikosaponin a significantly improved hepatic antioxidant status and suppressed malondialdehyde formation. Therefore, supplementation with curcumin and/or saikosaponin a protects against CCl(4)-induced liver injury by attenuating hepatic lipids and lipid peroxidation and enhancing antioxidant defense. Curcumin and saikosaponin a had no additive effects on hepatoprotection except for greater improvement in the total glutathione level and antioxidant status.     

黑米花色苷对四氯化碳亚急性肝损伤的保护作用及其机制

目的研究黑米皮花色苷(black rice anthocyanins,BRA)对CCl4亚急性肝损伤小鼠的保护作用。方法NIH小鼠60只,随机分为:对照组、CCl4模型组、黑米花色苷低、中、高剂量组(BRA-L0.40g/kgbw、BRA-M0.80g/kgbw、BRA-H1.60g/kgbw)共5组。饲养前3w内,除对照组外的其他4个组动物均腹腔注射四氯化碳(CCl4)玉米油溶液。每周2次,共3w,诱导化学性亚急性肝损伤动物模型。饲养7w后,测定各组动物血清谷丙转氨酶(ALT)和谷草转氨酶水平(AST),血清和肝脏中脂质过氧化产物丙二醛(MDA)含量、抗氧化酶活性及总抗氧化能力,用ELISA法分析BRA对各组动物血清中DNA主要氧化产物8-羟基脱氧鸟苷(8-hydroxy-2'-deoxyguanosine,8-OHdG)的影响,通过HE染色观察肝组织病理学变化。结果摄入BRA后的各剂量组,CCl4诱导的亚急性肝损伤小鼠的ALT、AST活性较模型组显著降低(P<0.05),血清和肝脏中MDA的生成量显著减少(P<0.05),SOD、GSH-Px活性明显增强(P<0.05),肝脏组织的总抗氧化能力(T-AOC)显著增强(P<0.05);摄入高剂量BRA,8-OHdG的含量显著降低(P<0.05);由CCl4引起的肝脏组织气球样变、脂肪变性,炎症浸润等病理学损伤,喂食BRA后,均可得到明显改善。结论BRA对CCl4诱导的亚急性肝损伤具有保护作用,这一作用与其抗氧化活性有关。     

Effect of fenugreek seed extract on adriamycin-induced hepatotoxicity and oxidative stress in albino rats

The purpose of this work was to evaluate the effect of aqueous extract of fenugreek seeds against hepatotoxicity induced in albino rats by the anticancer drug adriamycin (ADR). Animals were given single dose of ADR (10?mg/kg body weight) and were killed after 2 and 4 weeks. Liver of ADR-treated animals showed histopathological and biochemical alterations. The histopathological changes include hepatic tissue impairment, cytoplasmic vacuolization of the hepatocytes, congestion of blood vessels, leucocytic infiltrations and fatty infiltration. Moreover, the expression of proliferating cell nuclear antigen was increased in ADR-treated rats. The liver enzymes, aspartate aminotransferase (ALT) and alanine aminotransferase (AST) were increased in the sera of treated rats. Moreover, ADR significantly increased the concentration of malondialdehyde (MDA) and decreased the activities of superoxide dismutase (SOD) and catalase (CAT) in hepatic tissue. Treating animals with ADR and aqueous extract of fenugreek (0.4?g/kg body weight) seeds led to an improvement in histological and biochemical alterations induced by ADR. The biochemical results showed that AST and ALT appeared normal together with reduction in the level of MDA (lipid peroxidation marker) and increase in SOD and CAT activities. It was concluded from this study that the aqueous extract fenugreek seeds has a beneficial impact on ADR-induced hepatotoxicity due to its antioxidant effect in albino rats.     

Momordin Ic and oleanolic acid from Kochiae Fructus reduce carbon tetrachloride-induced hepatotoxicity in rats

Hepatoprotective effects of momordin Ic and oleanolic acid obtained from Kochiae Fructus (KF), the fruit of a traditional Oriental medicinal plant, were evaluated against carbon tetrachloride (CCl4)-induced liver damage in rats. Male Sprague-Dawley rats were divided into four groups: control, CCl4-treated, CCl4 plus momordin Ic-treated (MMDIc-CCl4), and CCl4 plus oleanolic acid-treated (OAA-CCl4). Momordin Ic (30 mg/kg of body weight) and oleanolic acid (30 mg/kg of body weight) were orally administered once a day for 14 days. A mixture of 0.2 mL/100 g of body weight of CCl4 in olive oil (1:1, vol/vol) was injected 30 minutes after the final administration of momordin Ic and oleanolic acid. The momordin Ic and oleanolic acid pretreatments resulted in significantly lower serum transaminase, lactic dehydrogenase, and gamma-glutamyltransferase levels in the CCl4-treated rats. The CCl4-treated rats had significantly lower activities of glutathione, glutathione reductase, glutathione S-transferase, superoxide dismutase, catalase, and glutathione peroxidase. However, pretreatment with momordin Ic and oleanolic acid reduced the effect of CCl4 and helped maintain levels of the enzymes. Pretreatment with momordin Ic and oleanolic acid resulted in significantly lower production of aminopyrine N-demethylase and aniline hydroxylase in the CCl4-treated rats. Pretreatment with momordin Ic resulted in lower catalase and aminopyrine N-demethylase activity induction by CCl4, towards normalization. Momordin Ic and oleanolic acid obtained from KF appear to contribute to alleviating the adverse effects of CCl4 treatment by enhancing the hepatic antioxidant defense system.     

Hepatoprotective activity of purified fractions from Garcinia kola seeds in mice intoxicated with carbon tetrachloride

The hepatoprotective activity of kolaviron (KV), a biflavonoid complex from Garcinia kola seeds, and its purified fractions was investigated in mice intoxicated with carbon tetrachloride (CCl(4)). The ability of vitamin E to attenuate the toxicity was also examined. KV was extracted from powdered seeds of G. kola and then separated by thin-layer chromatography into three fractions--Fraction I (FI), Fraction II (FII), and Fraction III (FIII), with ratio of fronts values of 0.48, 0.71, and 0.76, respectively. Pretreatment with KV, FI, and FII at a dose of 100 mg/kg of body weight for 2 weeks and then challenge with CCl(4) at a dose of 1.2 g/kg of body weight, three times a week for 2 consecutive weeks, decreased the CCl(4)-induced increase in activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) by 31%, 30%, and 31% and 41%, 55%, and 42%, respectively. CCl(4) intoxication also caused a significant (P < .05) accumulation of lipid peroxidation (LPO) products as revealed by the formation of the thiobarbituric acid-reactive substances: CCl(4) induced LPO levels in serum and microsomes by 112% and 89%, respectively. However, pretreatment with KV, FI, and FII decreased LPO levels in serum by 31%, 41%, and 40% and in microsomes by 48%, 39%, and 35%, respectively. Vitamin E was protective in reducing the CCl(4)-induced increase in levels of AST, ALT, and gamma-glutamyl transferase as well as LPO. Furthermore, CCl(4) intoxication significantly (P < .05) decreased the activities of microsomal glucose-6-phosphatase, aniline hydroxylase, and cytosolic glutathione-S-transferase (GST). While pretreatments with KV, FI, and FII were able to ameliorate the levels of glucose-6-phosphatase and GST, there were no significant (P > .05) effects on the levels of aniline hydroxylase and DT-diaphorase. This study confirms that FI and FII from KV enhanced recovery from CCl(4)-induced hepatotoxicity by decreasing the extent of LPO and also inducing the levels of phase II enzyme (GST). These fractions are responsible for the observed antihepatotoxic effect of KV.     

Protective effects of extracts of Vernonia amygdalina, Hibiscus sabdariffa and vitamin C against radiation-induced liver damage in rats

The radioprotective efficacy of methanolic extracts of leaves of Vernonia amygdalina (VA) and Hibiscus sabdariffa (HS), and vitamin C (VIT C) against gamma radiation (4 Gy) induced liver damage was studied in male Wistar albino rats. VIT C was administered at a dose of 250 mg/kg body weight, while VA and HS were administered at doses; 200, 400 and 800-mg/kg body weight, orally for 4 weeks prior to radiation and 5 weeks after irradiation. The rats were sacrificed at 24 hours and 5 weeks after irradiation. Treatment with VIT C and VA (800 mg/kg) significantly (p < 0.05) decreased the gamma radiation-induced increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities at 24 hours after irradiation, whereas, HS (400 mg/kg) significantly (p < 0.05) decreased the serum ALT activity only. Similarly, treatment with VIT C and VA (800 mg/kg) significantly (p < 0.05) decreased the serum conjugated bilirubin levels by 56% and 29%, respectively at 24 hours. Furthermore, VIT C, VA and HS significantly (p < 0.05) decreased the levels of serum lipid peroxidation (LPO) and increased the hepatic superoxide dismutase (SOD) activities at 24 hours. Treatment for 5 weeks after irradiation with VITC, VA and HS significantly (p < 0.05) decreased the levels of unconjugated bilirubin, while VIT C and VA alone decreased the levels of conjugated bilirubin. Furthermore, treatment with VA (400 and 800 mg/kg) decreased the serum ALT activities by 25% and 34%, respectively, at 5 weeks after irradiation. Similarly, alkaline phosphatase and LPO levels were significantly (p < 0.05) attenuated following treatment with VIT C and VA (400 and 800 mg/kg) at 5 weeks after irradiation. In addition, treatment with VIT C, VA (800 mg/kg) and HS (400 and 800 mg/kg) significantly (p < 0.05) elevated the levels of reduced glutathione (GSH) by 61%, 56%, 41% and 44%, respectively, at 5 weeks. Similar elevation of antioxidant enzymes; SOD, glutathione-s-transferase and catalase were obtained in animals treated with VIT C and extracts at 5 weeks. Taken together, the results suggest that the extracts of VA and HS, and VIT C could increase the antioxidant defense systems and may probably protect animals from radiation-induced liver damage.     

Increase of ceramide in the liver and plasma after carbon tetrachloride intoxication in the rat

In fulminant hepatic failure, various toxins causing multi-organ failure increase in plasma. As a novel toxin, levels of ceramide, a well-studied lipid mediator of apoptosis, were determined by LC-MS/MS in the liver and plasma of carbon tetrachloride (CCl4)-intoxicated rats. After 6 h of oral administration of CCl4 (4 mL/kg body weight as a 1:1 mixture of CCl4 and mineral oil) to rats, extensive hepatic failure occurred as evidenced by a severe elevation in plasma AST and ALT. The liver concentration of major ceramide components (C16:0, C24:0, C24:1, C18:0, C22:0, and C24:2 in decreasing order), and the sum of these ceramides increased significantly 2 h after CCl4 intoxication compared to that in the control group given mineral oil. The total ceramide concentration in the plasma was also increased to 4.1 times that in the control 24 h after administration of CCl4. In conclusion, the early increase in liver ceramides may contribute to hepatic cell death and the increase in plasma ceramides during fulminant hepatic failure may cause damage in other organs including the brain and kidney.     

奶蓟益肝片对四氯化碳肝损伤保护作用效果观察

目的探讨奶蓟益肝片对四氯化碳（CCl4）肝损伤的保护作用。方法将46只动物随机分成阴性对照组、CCl4对照组及0.13、0.25g/kg两个剂量组,剂量组每天灌胃给予奶蓟益肝片。30d后,CCl4对照组及剂量组以0.01ml/g的剂量一次性经腹腔注射给予0.125?l4。24h后处死动物,测定血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）水平,肝脏进行病理组织学检查。结果0.25g/kg剂量组的ALT、AST水平降低,与CCl4对照组比较,差异有显著性（P〈0.05）。0.25g/kg剂量组发生肝细胞坏死的动物例数减少,病变程度减轻,肝细胞坏死评分降低,与CCl4对照组比较,差异亦有显著性（P〈0.05）。结论奶蓟益肝片对CCl4化学性肝损伤具有保护作用。     

Protective effect of BP 2-94, a histamine H3-receptor agonist prodrug, in a model of carbon tetrachloride-induced hepatotoxicity in rats

BP 2-94 is a prodrug of the H3-receptor agonist (R)-alpha-methylhistamine [(R)-alpha-MeHA]. BP 2-94 displayed anti-inflammatory, antinociceptive and ulcero-protective properties in experimental animals. AIM: The aim of the present study was to investigate the effect of BP 2-94 in a model of carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. MATERIALS AND METHODS: In order to investigate the effect of BP 2-94 it was applied to rats either alone (20, 40 and 60 micromol kg(-1), 4 days) or as a pretreatment (20, 40 and 60 micromol kg(-1), 4 days) before the application of CCl4 (0,2 ml kg(-1), 2 days). RESULTS: BP 2-94 in the tested doses did not cause significant changes in the plasma aspartate transaminase (AST) and alanine transaminase (ALT) activities and the liver microscopic appearance was normal. Hepatocyte damage, as evident by local areas of liver necrosis and elevated levels of plasma AST and ALT, occurred in rats following acute exposure to CCl4 (0,2 ml kg(-1), 2 days). BP 2-94 applied as a pretreatment dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of plasma AST and ALT activities in response to CCl4. CONCLUSIONS: BP 2-94 had a hepatoprotective effect in a model of CCl4-induced toxicity in rats. This effect might be due the H3-agonistic activity of its active metabolite (R)-alpha-MeHA.     

善维片对化学性肝损伤保护作用的试验研究

目的：了解善维片对大鼠急性化学性肝损伤的保护作用，探讨评价保健品保肝作用实验的适宜观察时间。方法：按照卫生部《保健食品功能学评价程序和检验方法》进行，并比较四氯化碳（CCl4）染毒后第48小时和第5天处死动物对各项指标的影响。结果：与肝损伤模型对照组相比，染毒后第48小时，善维片三个剂量组动物血清ALT（丙氨酸氨基转移梅）水平均有显著降低（P＜0．05 ），中、高剂量组血清AST（天门冬氨酸氨基转移酶）水平也有显著降低（P＜0．05），受试物各剂量组均改善肝细胞退行性变，且高剂量组可明显减轻CCl4引起的肝细胞坏死（P＜0．05）。而染毒后第5天时，包括肝损伤模型组在内的各实验组大鼠的血清ALT和AST活性均已与对照组差异无显著性，提示CCl4致急性肝损伤 此时已得到全面修复。结论：善维片对CCl4致急性肝损伤具有预防作用。评价受试物的保肝作用时，以CCl4染毒后第48小时处死动物观察肝脏功能学和形态学变化为宜。     

载硒酵母对小鼠化学性肝损伤的影响

观察不同剂量（３０，６０，９０ｍｇ／ｋｇ）载硒酵母（ｓｅｌｍｉｎｍ－ｅｎｒｉｃｈｅｄｙｅａｓｔ，ＳＥＹ）ｉｇ７天对ＣＣｌ４和Ｄ－Ｇａｌ－Ｎ引起的化学性肝损伤的保护作用。结果发现：ＳＥＹ６０ｍｇ／ｋｇ可降低ＣＣｌ４所致血清ＡＬＴ的升高，各剂量组均可降低Ｄ－Ｇａｌ－Ｎ所致血清ＡＬＴ和ＡＳＴ的升高，ＳＥＹ３０ｍｇ／ｋｇ可减轻Ｄ－Ｇａｌ－Ｎ所致肝病理损伤，各剂量组ＳＥＹ均可降低Ｄ－Ｇａｌ－Ｎ所致肝匀浆ＭＤＡ含量升高。提示ＳＥＹ在一定程度上可减轻ＣＣｌ４和Ｄ－Ｇａｌ－Ｎ的化学性损伤，其作用机制可能与抗氧化作用有关。     

胶原蛋白多肽-铬(Ⅲ)螯合物对四氧嘧啶致小鼠肝脏损伤的保护作用

目的:研究胶原蛋白多肽-铬(Ⅲ)螯合物(CPCC)对四氧嘧啶致小鼠肝脏损伤的保护作用。方法:将小鼠随机分成正常、模型和胶原蛋白多肽-铬(Ⅲ)螯合物三组,正常组与模型组灌胃蒸馏水,CPCC组灌胃CPCC水溶液(Cr3+40μg/kg?d),灌胃4w后模型组和CPCC组腹腔注射四氧嘧啶造模,测定小鼠肝指数及血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)和碱性磷酸酶(ALP)活性,测定肝匀浆中超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量,同时观察肝组织病理变化。结果:CPCC组可以非常显著地降低造模后小鼠肝指数及血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)和碱性磷酸酶(ALP)活性。肝匀浆SOD、GSH-Px活力及丙二醛(MDA)含量均显著下降,肝细胞损伤明显减轻。结论:CPCC对四氧嘧啶致小鼠肝脏损伤有保护作用。     

富硒酵母对铜负荷导致小鼠肝损伤的保护作用

目的探讨富硒酵母对小鼠铜负荷致肝损伤的保护作用。方法采用过量(512mg/kgbw·d)硫酸铜灌胃致小鼠肝损伤后,给予低、中、高(20、40、60mg/kgbw·d)的富硒酵母4w,观察补硒对肝脏丙二醛(MDA)含量、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性以及血清和肝组织中铜含量的影响,并进行肝脏病理组织学检查和肝细胞凋亡检测,同时测定血清中谷丙转氨酶(ALT)和谷草转氨酶(AST)活性。结果过量硫酸铜能导致小鼠肝脏损伤,与低、高剂量富硒酵母添加组相比,补充中剂量富硒酵母能显著缓解这种损伤,表现为血清和肝组织的铜含量显著降低,肝组织中SOD、GSH-Px活性增强,MDA含量减少,肝细胞凋亡显著减少。结论适量的富硒酵母能降低铜负荷导致的小鼠肝功能损伤,其机制可能与减轻铜离子介导的脂质过氧化有关。     

纳米二氧化钛经口暴露对小鼠肝脏的影响

目的 探讨纳米二氧化钛(TiO2 NPs)经口暴露后对小鼠肝脏的影响。方法 60只健康雄性ICR小鼠随机分为对照组、TiO2 NPs (10、50、100) mg/kg·BW染毒组,连续灌胃30 d后,颈椎脱臼处死小鼠,计算小鼠肝脏系数,观察小鼠肝脏组织病理学切片,测定肝组织匀浆中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST),超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH - PX)、总抗氧化能力(T - AOC)活力以及丙二醛(MDA)含量。结果 与对照组相比,各染毒组小鼠肝脏系数差异无统计学意义(P＞0.05);病理学切片观察各染毒组肝脏组织均可见不同程度肝组织损伤;随着TiO2 NPs染毒剂量的增加,ALT、AST活力以及MDA含量在50、100 mg/kg·BW组升高,SOD活性在100 mg/kg·BW组降低,GSH - PX活性在50、100 mg/kg·BW组降低,T - AOC水平在10、50、100 mg/kg·BW组均降低,差异均具有统计学意义(P＜0.05)。结论 经口暴露TiO2 NPs,可使小鼠肝脏发生氧化应激反应,造成肝脏氧化损伤,并最终导致小鼠肝脏组织结构及功能破坏,具有一定的肝脏毒性作用。