前列腺素E1对输尿管梗阻大鼠肾间质纤维化及转化生长因子β1mRNA表达的影响

目的：探讨前列腺素E1（PGE1）拮抗肾间质纤维化的作用。方法：建立单侧输尿管梗阻（UUO）大鼠肾小管间质病变模型，应用原位杂交、病理形态学观察、生化分析等技术，研究PGE1用药后肾组织中转化生长因子β1（TGFβ1）mRNA的表达，肾小管间质病变及羟脯氨酸含量的变化。结果：大鼠UUO术后3d，肾间质水肿、单个核细胞浸润；14d后肾小管萎缩，间质纤维增生，间质面积增宽，伴随肾皮质中羟脯氨酸含量升高及TGFβ1mRNAg表达增多。后者的峰值出现先于羟脯氨酸峰值及间质面积增宽。PGE1可下调TGFβ1mRNA表达及羟脯氨酸含量，抑制间质中单个核细胞浸润。结论：PGE1改善UUO大鼠肾间质纤维化的原因至少与抑制单个核细胞浸润及TGFβ1mRNA表达有关。     

福辛普利保护糖尿病肾病及其对肾组织TGFβ1 mRNA表达的影响

目的探讨福辛普利对糖尿病肾小球病变的保护作用与机制。方法建立糖尿病大鼠模型,分为正常对照组(A组)、糖尿病组(B组)、福辛普利治疗组(C组),C组1 w后给予福辛普利灌胃给药。检测各组第1、2、4、12周血糖、24 h尿视黄醇结合蛋白以及尿白蛋白排泄率;分别于第4、12周每组各处死5只大鼠,计算肾脏肥大指数,检测皮质TGFβ1mRNA水平;检查肾小球基底膜、系膜区病理改变。结果第1周B和C组尿白蛋白排泄率与A组差异无统计学意义;第2、4、12周尿白蛋白和视黄醇结合蛋白排泄率,B组均显著高于A组;第4、12周,B组大鼠肾皮质TGFβ1mRNA表达较A组显著增加,C组TGFβ1mRNA表达明显低于B组,但较A组表达量仍然增加;B组肾小球毛细血管基底膜增厚;C组肾小球毛细血管基底膜也有不规则增厚,较同时期B组减轻。结论肾脏TGFβ1mRNA表达的上调可能是糖尿病肾病的发生机制之一,福辛普利对糖尿病肾病具有确切的保护作用。     

番茄红素对CCl_4致大鼠肝肾抗氧化功能改变的保护作用

目的观察四氯化碳(CCl4)对大鼠肝肾抗氧化功能的影响及番茄红素的保护作用。方法大鼠灌胃番茄红素4周后,以CCl4腹腔注射24h后处死,测定血清和肝、肾匀浆的超氧化物歧化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-Px)活力、丙二醛(MDA)含量、谷胱肝肽(GSH)含量及总抗氧化能力(T-AOC)。结果与CCl4组相比,番茄红素组大鼠血清和肝、肾组织的SOD活性、GSH-Px活力上升,MDA含量降低,GSH含量升高,T-AOC升高(P<0·05)。结论番茄红素可以提高大鼠肝和肾的抗氧化能力。     

铁死亡参与四氯化碳致肝纤维化发病过程的研究

目的 探讨铁死亡是否参与CCl4致肝纤维化发病过程。方法 小鼠分为对照组和CCl4组。采用腹腔注射法造模,每隔2 d给药1次,共8次,造模完成后隔2 d处死。通过HE、MASSON和天狼星红染色评价CCl4致小鼠肝损伤及纤维化情况;铁离子检测试剂盒检测小鼠肝组织铁离子含量;MDA检测试剂盒检测小鼠肝组织MDA含量;免疫荧光法观察小鼠肝组织中MDA含量;谷胱甘肽/氧化型谷胱甘肽(GSH/GSSG)评价小鼠肝组织脂质过氧化情况;通过Western Blot和RT - qPCR评价谷胱甘肽过氧化物酶4(GPX4)、铁蛋白(Ferritin)的蛋白和mRNA表达水平。结果 通过HE染色、MASSON染色和天狼星红染色发现,CCl4引起小鼠肝细胞排列紊乱,炎症细胞浸润,纤维化隔片形成。而对照组没有显著的病理变化;CCl4组小鼠肝组织铁离子含量(2.83±0.81) μmol/g较对照组小鼠肝组织铁离子含量(1.54±0.19) μmol/g增加(t = 5.415,P＜0.001);CCl4组MDA荧光强度高于对照组;CCl4组MDA含量(0.74±0.13) nmol/mg较对照组MDA含量(0.21±0.06) nmol/mg增加(t = 15.650,P＜0.001);GSH/GSSG在CCl4组(1.29±0.19)较对照组(1.90±0.16)降低(t = 10.580,P＜0.001);在CCl4组GPX4蛋白相对表达水平(0.27±0.07)较对照组(0.42±0.10)降低(t = 3.000,P = 0.013)。CCl4组Ferritin蛋白相对表达水平(0.18±0.06)较对照组(0.30±0.06)降低(t = 3.571,P = 0.005);CCl4组Ferritin mRNA相对表达水平(1.83±0.60)较对照组(0.84±0.30)降低(t = 4.420,P＜0.001)。CCl4组GPX4 mRNA相对表达水平(1.10±0.45)较对照组(3.54±0.87)降低(t = 7.385,P＜0.001)。结论 铁死亡参与了四氯化碳致肝纤维化的发病过程。     

儿茶素类化合物对四氯化碳致大鼠慢性肝损伤的保护作用

目的　观察儿茶素类化合物保肝降酶的作用。方法　制备大鼠的四氯化碳 (CCl4)慢性肝损伤模型 ,观察儿茶素类化合物对肝损伤大鼠血清丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST)、丙二醛 (MDA)等的影响 ,以及肝组织羟脯氨酸含量和肝脏组织结构的变化。结果　儿茶素类化合物给药 2个月后 ,中、高剂量给药组 (10 0 ,2 0 0mg/kg)均能降低血清ALT的活力以及脂质过氧化产物MDA和肝组织羟脯氨酸的含量 (P <0 0 1或P <0 0 5 ) ,其降低肝组织羟脯氨酸含量的作用与联苯双酯相当。肝组织的病理改善情况两药相似 ,而抗膜脂质过氧化作用优于联苯双酯。结论　儿茶素类化合物具有保护化学性肝损伤作用 ,有降低转氨酶活力、减轻肝脏病理损伤的作用     

维生素对免疫性肝纤维化大鼠的抗纤维化作用

目的研究几种维生素对肝纤维化大鼠的影响并比较其疗效。方法用维生素A(VA),β-胡萝卜素(β-CAR),维生素C(VC)和维生素E(VE)干预免疫性肝纤维化大鼠,通过肝组织病理学、肝纤4项(透明质酸、层粘蛋白、Ⅲ型前胶原和Ⅳ型胶原)、转化生长因子β1(TGFβ1)mRNA和金属蛋白酶组织抑制因子-1(tissue inhibitor of met-alloproteinase,TIMP-1)mRNA在肝组织中的表达等指标判定并比较其疗效。结果VA、β-CAR、VC和VE组的肝纤维化半定量计分分别为8.00±4.14,6.25±4.47,13.13±7.54,5.06±3.60,除VC外,其他3种维生素均对肝纤维化大鼠肝组织的病理变化有明显的改善作用;VA、β-CAR和VE组的血清肝纤4项综合得分均明显低于模型组,且VE组得分低于VA、与β-CAR组差异无统计学意义;VA,β-CAR和VE均能明显抑制肝纤维化大鼠肝组织TGFβ1mRNA的表达,VE还能明显抑制TIMP-1 mRNA的表达。结论VA、β-CAR和VE均有抗肝纤维化作用,且VE的效果优于VA,与β-CAR差异无统计学意义,VC无效。     

氯沙坦对日本血吸虫病肝纤维化小鼠αSMA及TGFβ1的影响

目的探讨氯沙坦影响日本血吸虫病鼠早期肝纤维化的部分相关机制。方法将36只昆明小鼠随机分为正常对照组,感染对照组及氯沙坦组,采用日本血吸虫尾蚴35条/只鼠攻击感染小鼠建立血吸虫性肝纤维化模型,氯沙坦10 mg/(kg.d),灌胃,1次/d,连续6周,HE染色观察肝组织病理学改变;放射免疫法检测血清中透明脂酸(HA)含量,SP法检测α平滑机动蛋白(SMA),金属蛋白酸因子(TIMP)-1在肝组织中的表达;实时荧光定量法检测AT1R mRNA及转化生长因子β1(TGFβ1)mRNA的含量。结果氯沙坦组小鼠肝组织病理学改善明显;与感染组相比,氯沙坦组小鼠血清中HA含量降低,肝组织αSMA、TIMP-1的水平和AT1R mRNA、TGF1βmRNA的相对量均显著下降(P0.05)。结论研究结果显示,氯沙坦改善肝组织病理学改变,降低血清中HA含量,与其能减少αSMA、TIMP-1的表达,下调AT1R mRNA、TGFβ1mRNA的水平有关。     

β-雌二醇纳米粒抗肝纤维化的效果及对TGF—β1和CTGF的影响

目的研究自行制备的肝靶向聚氰基丙烯酸正丁酯β-雌二醇纳米粒（E2-PBCA—NP）抗肝纤维化的效果，以及对猪血清诱导的肝纤维化动物模型肝脏TGF—β1、CTGF表达的影响。方法将SD大鼠随机分成5组，除正常对照外，其余4组均腹腔注射猪血清（0．5ml／次，2次／周）构建大鼠免疫性肝纤维化模型。β-雌二醇治疗组、β雌二醇纳米粒治疗组、空白纳米粒组在第9周给予腹腔注射干预药物，2次／周；在12周末处死老鼠，Masson染色观察肝脏纤维化改变，RT—PCR检测肝组织中TGF-β1和CTGFmRNA的含量，免疫组化观察TGF-β1及CTGF蛋白的表达。结果与模型组比较，β-雌二醇纳米粒和β-雌二醇治疗组均能显著逆转猪血清诱导的肝纤维化，肝纤维化分期好转（P〈0．05）；β-雌二醇纳米粒治疗组与β-雌二醇治疗组2组比较差异有统计学意义（P〈0．05）；β-雌二醇纳米粒治疗组与β-雌二醇治疗组肝组织TGF—β1、CTGFmRNA和蛋白的表达下降（P〈0．01），但β-雌二醇和β-雌二醇纳米粒治疗组之间比较差异无统计学意义（P〉0．05）。结论纳米化后的β-雌二醇仍具有抗肝纤维的作用，与无纳米化β-雌二醇比较，抗肝纤维的作用更强。β-雌二醇纳米粒能够抑制TGF—β1及其下游信号CTGF的表达。     

天然植物提取物抗CCl_4所致大鼠慢性肝损伤的病理研究

目的　研究天然植物提取物对CCl4 所致大鼠慢性肝损伤的病理影响。方法　采用 4 0 %CCl4 2次 周腹腔注射 (2ml kgBW)建立慢性肝损伤模型 ,干预组在造模同时给予天然植物提取物 (0 2 7g kgBW)灌胃 ,7周后取肝组织 ,常规病理切片 ,HE、Masson、James染色后 ,光镜下观察病理改变 ,电镜下观察超微结构变化。结果　天然植物提取物能有效拮抗CCl4 诱导的大鼠肝组织内网状纤维、胶原纤维的形成 ,有效减轻CCl4 所致的肝组织病理改变。结论　天然植物提取物对CCl4 所致大鼠慢性肝损伤有一定防治作用     

硫代乙酰胺诱导的肝硬化大鼠蛋白质代谢变化

目的 探讨硫代乙酰胺诱导的肝硬化大鼠血浆氨基酸谱和GH／IGF-1l轴变化。方法 正常组和肝硬化组大鼠各6只，测大鼠肝功能、血糖、血浆氨基酸谱和血清GH、IGF-1、IGFBP-3水平，用RT-PCR法检测肝ALBmRNA、IGF-1mRNA、IGFBP-3mRNA表达。肝组织行HE染色和Ki67免疫组化染色。结果 与正常组比较，肝硬化组大鼠血清AST、ALT、ALP明显升高；血浆总氨基酸及AAA明显升高，BCAA及Fischer值明显降低；血清GH水平明显升高，而血清IGF-1、IGFBP-3水平明显降低，肝ALB mRNA、IGF-1 mRNA、IGFBP-3 mRNA表达水平也明显降低、肝硬化组大鼠镜下见假小叶形成，肝Ki67指数明显高于正常组。结论 硫代乙酰胺诱导的肝硬化大鼠血浆氨基酸谱和GH／IGF-1轴的变化与人类肝硬化大体相似，是研究肝硬化蛋白质代谢的理想模型。     

硫化氢对肝硬化胶原蛋白生成的影响

观察硫化氢(H2S)对肝硬化胶原蛋白形成的影响,探明其在肝硬化形成过程中的作用。方法采用四氯化碳(CCl4)复合因素法建立肝硬化大鼠模型。选取Wistar大鼠20只,按数字表法随机分成正常对照组6只、肝硬化遭模组(造模组)7只和肝硬化造模并加硫化氢钠(NaHS)组(观察组)7只,对观察组进行腹腔注射NaHS 1.4 μ...     

不同维生素E水平对四氯化碳肝损害的影响

方法：大鼠经２９天喂养造成不同ＶＥ水平的模型。一次腹腔注射０．６５ｍｌ／ｋｇ四氯化碳（ＣＣｌ４）。结果：２４小时后，肝匀浆中丙二醛（ＭＤＡ）水平明显增高，ＶＥ缺乏组升高更明显，ＶＥ添加组ＭＤＡ明显下降。肝匀浆中总巯基、非蛋白巯基、蛋白巯基在染毒后未发生明显改变，也未发现不同水平ＶＥ对其有影响。ＣＣｌ４染毒后，血清丙氨酸转氨酶（ＡＬＴ）明显升高：随着饲料ＶＥ水平增高，ＡＬＴ上升幅度增大，病理检查变性坏死面积稍有增加，提示ＶＥ似有促进肝细胞坏死作用，脂质过氧化可能不是ＣＣｌ４致肝细胞坏死的唯一机理。肝匀浆甘油三酯（ＴＧ）在染毒后明显升高，说明ＴＧ在肝脏中蓄积。饲料ＶＥ增高，其蓄积程度减轻，但对血清中ＴＧ影响不大。ＶＥ也可降低血清中胆固醇的含量。结论：ＶＥ有预防ＣＣｌ４所致ＴＧ在肝中蓄积和脂肪肝形成的作用。     

补充VE、Se对大鼠肝纤维化和抗氧化功能影响的研究

目的 :　探讨维生素 E(VE)、硒 (Se)对 CCl4 大鼠肝纤维化和抗氧化功能的影响。方法 :　 48只 SD大鼠随机分为 3组。模型组 ,采用腹腔注射 5 0 % CCl4 和橄榄油混合制剂的方式建立大鼠肝纤维化模型 ,喂饲标准饲料 ;干预组 ,处理方式同前 ,并在大鼠饲料中加 VE(2 5 0 mg/kg )和 Se(0 .2 mg/kg)进行营养干预 ;对照组 ,腹腔注射生理盐水 ,喂饲标准饲料。全部动物于处理 8w后处死。通过 HE常规染色和 Masson三色胶原染色对肝组织切片进行病理组织学检查 ;同时分别检测大鼠体内各种抗氧化指标和其他肝纤维化指标 ,并观察其变化。结果 :　干预组大鼠抗氧化能力有显著提高 ,表现在肝组织和血清 SOD、红细胞 GPX活性均显著高于模型组 ,而肝组织和血清MDA水平显著低于模型组。同时 ,干预组大鼠的肝纤维化程度显著低于模型组 ,体现在血清 ALT、AST水平、肝组织羟脯氨酸含量都显著低于模型组 ;组织病理学检查显示肝脏胶原纤维增生程度也显著低于模型组。结论 :　补充适量 VE和 Se具有提高机体抗氧化的能力 ,显著减轻肝脏胶原纤维的增生程度     

番茄红素对急性肝损伤大鼠抗氧化酶的影响

目的　观察四氯化碳急性中毒对大鼠机体抗氧化酶活力的影响及番茄红素 (lycopene ,LP)的保护作用。方法　大鼠灌胃番茄红素 ,4周后以四氯化碳腹腔注射 ,2 4h后处死 ,测定血清和肝匀浆的超氧化物岐化酶 (SOD)活性 ,谷胱甘肽过氧化物酶 (GSH Px)活力 ,丙二醛 (MDA)含量 ,还原型谷胱肝肽 (GSH)含量及总抗氧化能力 (T AOC)。结果　与模型组相比 ,各番茄红素组的大鼠血清和肝组织的SOD活性 ,GSH Px活力上升 ,MDA含量降低 ,GSH含量升高 ,T AOC升高 ,差异有统计学意义 (P <0 0 5 )。结论　番茄红素可以提高大鼠机体的抗氧化能力 ,减轻四氯化碳对机体造成的肝损伤。     

维生素A和β-胡萝卜素对大鼠肝纤维化的影响

目的 :　研究β-胡萝卜素对四氯化碳诱导的实验性大鼠肝纤维化的影响及其机制。方法 :　SD大鼠随机分为 4组。正常对照组 :给橄榄油溶液 1 ml/kg bw,9w;四氯化碳对照组 :给5 0 %CCl4 橄榄油溶液 1 ml/kg bw,每周两次皮下注射持续 9w;维生素 A和 β-胡萝卜素组 :注射5 0 %CCl4 橄榄油溶液 3 w后 ,分别给以维生素 A0 .1 g/kg bw,每周两次皮下注射 ,β胡萝卜素 1 5 0mg/kg bw,每周两次灌胃 ,持续 6 w,之后观察肝脏组织病理及超微结构 ;羟脯氨酸含量和 型胶原 RNA的表达水平。结果 :　 1 .普通病理切片显示 ,各治疗组中无明显肝细胞损害 ,纤维化程度计分明显低于四氯化碳对照组 (P<0 .0 5 ) ;超微结构显示维生素 A组的星形细胞中的脂滴数量明显多于正常对照和四氯化碳对照组 ;而β-胡萝卜素治疗组中脂滴数量多于四氯化碳对照组 ;治疗组间质中的胶原纤维亦明显减少 ;2 .治疗组羟脯氨酸含量亦明显低于四氯化碳对照组 (P<0 .0 5 ) ;3 .治疗组中的 型 α2 胶原的 RNA表达水平亦低于四氯化碳对照组。结论 :　维生素 A0 .1 g/kgbw每周两次皮下注射 ,持续 6 w和 β-胡萝卜素 1 5 0 mg/kg bw,每周两次灌胃 ,持续 6 w能降低由四氯化碳诱导的大鼠肝纤维化的程度 ,其作用途径可能与抑制肝脏星形细胞中的脂滴丢失有关?     

Ethanol and food deprivation induced enhancement of hepatotoxicity in rats given carbon tetrachloride at low concentration

Effects of chronic ethanol consumption and one day food deprivation on the hepatotoxicity of low dose carbon tetrachloride (CCl4; 0 to 100 ppm inhalation for eight hours) in rats were investigated by using biochemical and histopathological methods. Liver malondialdehyde (MDA) contents were significantly increased by exposure to 5 ppm to 50 ppm CCl4 in ethanol treated rats or by exposure to 25 ppm to 50 ppm CCl4 in food deprived rats but not in rats without ethanol or food deprivation. The MDA concentrations reached a maximum at 10 ppm and 50 ppm CCl4 in ethanol treated and food deprived rats, respectively, and decreased to the non-exposed concentration at 100 ppm CCl4. At greater than or equal to 50 ppm CCl4 plasma MDA contents increased significantly only in ethanol treated rats. None of the exposure concentrations influenced plasma glutamic-oxaloacetic transamidase (GOT) and glutamic-pyruvic transaminase (GPT) activities in rats that were only exposed to CCl4 whereas exposure to 10 ppm or higher concentrations combined with ethanol increased both activities. To a lesser extent food deprivation combined with exposure to greater than or equal to 25 ppm CCl4 had the same effect. No histopathological changes were found in the liver of rats exposed to less than or equal to 10 ppm CCl4, and only a few ballooned hepatocytes were seen in centrilobular areas when exposure was 25 ppm or higher. The presence of ballooned and hepatocytes became a regular feature of mid-zonal areas in ethanol treated rats and in the centrilobular areas of food deprived rats after exposure to /=25 ppm and >/=50 ppm respectively. These results indicate that consumption of ethanol and food deprivation potentiate CCl(4) induced hepatic damage even at low concentrations of CCl(4) by promoting lipid peroxidation. Thus heavy drinking may be a risk factor for CCl(4) induced hepatic damage even though the CCl(4) concentration is as low as the threshold limit value.     

补充抗氧化剂对急性肝损伤大鼠肝星型细胞zf-9mRNA表达的影响

目的:探讨经膳食补充抗氧化剂维生素E(VE)、硒及槲皮素对大鼠急性肝损伤早期肝脏星型细胞激活相关性基因zf-9mRNA表达的影响。方法:90只SD大鼠随机分为正常对照组、病理对照组、VE和硒补充组及槲皮素补充组。通过灌胃分别补充VE、Se(VE20mg/kg bw·d,硒16μg/kgbw﹒d)和槲皮素(50mg/kg bw·d)2w后,腹腔内注射CCl4造成急性肝损伤,分别于注射后的3、6、12和24h检测抗氧化状态及肝功能;用胶原酶和链霉蛋白酶灌注肝脏并分离急性肝损伤期各时间点的肝星型细胞,应用半定量聚合酶链反应(RT-PCR)研究zf-9mRNA的表达。结果:膳食补充VE、硒和槲皮素可显著减少急性肝损伤大鼠血清MDA水平,增强SOD活性,保护肝功能;下向调控肝星型细胞激活早期zf-9mRNA的表达。结论:膳食补充抗氧化剂VE、硒及槲皮素可有效地调控HSC激活相关性基因zf-9mRNA的表达。     

Preventive effect of D-002, a mixture of long-chain alcohols from beeswax, on the liver damage induced with CCl4 in rats

D-002 is a mixture of higher aliphatic primary alcohols purified from beeswax with antioxidant effects. Acute hepatotoxicity induced with CCl4 in rats has been related to increased hepatic lipid peroxidation and prevented with some antioxidants. This study investigated whether D-002 could prevent the acute CCl4-induced hepatotoxicity in rats. Animals were randomly distributed into four groups: a negative control treated orally with the vehicle and three groups injected with CCl4 (1 mL/kg) and treated orally either with the vehicle (positive control) or with D-002 (25 and 100 mg/kg). Eighteen hours after CCl4 dosing, rats were anesthetized, and livers were removed for histopathological studies. Some portions were taken and homogenized for assessing malondialdehyde (MDA) concentrations. Positive, but not negative, controls showed ballooned cells, swollen hepatocytes, and lipid-included hepatocytes, as well as necrotic areas and inflammatory infiltrates. D-002 (25 and 100 mg/kg) dose-dependently and significantly (P < .01) decreased the frequency of all abnormal liver cell types and increased that of normal hepatocytes compared with the positive controls, not showing necrotic areas or inflammatory infiltrates. D-002 dose-dependently decreased hepatic MDA levels, but only in the highest dose group were these levels significantly lower than in the positive control. In conclusion, D-002 effectively prevented the histological liver disturbances and lowered MDA levels, a marker of cellular lipid peroxidation, in rats treated with CCl4. Since increased liver lipid peroxidation has been postulated as a cause of CCl4-induced liver damage in rats, the preventive effects of D-002 could be due to its antioxidant action, but such a proposal still requires further research.     

Ethanol and food deprivation induced enhancement of hepatotoxicity in rats given carbon tetrachloride at low concentration.

Effects of chronic ethanol consumption and one day food deprivation on the hepatotoxicity of low dose carbon tetrachloride (CCl4; 0 to 100 ppm inhalation for eight hours) in rats were investigated by using biochemical and histopathological methods. Liver malondialdehyde (MDA) contents were significantly increased by exposure to 5 ppm to 50 ppm CCl4 in ethanol treated rats or by exposure to 25 ppm to 50 ppm CCl4 in food deprived rats but not in rats without ethanol or food deprivation. The MDA concentrations reached a maximum at 10 ppm and 50 ppm CCl4 in ethanol treated and food deprived rats, respectively, and decreased to the non-exposed concentration at 100 ppm CCl4. At greater than or equal to 50 ppm CCl4 plasma MDA contents increased significantly only in ethanol treated rats. None of the exposure concentrations influenced plasma glutamic-oxaloacetic transamidase (GOT) and glutamic-pyruvic transaminase (GPT) activities in rats that were only exposed to CCl4 whereas exposure to 10 ppm or higher concentrations combined with ethanol increased both activities. To a lesser extent food deprivation combined with exposure to greater than or equal to 25 ppm CCl4 had the same effect. No histopathological changes were found in the liver of rats exposed to less than or equal to 10 ppm CCl4, and only a few ballooned hepatocytes were seen in centrilobular areas when exposure was 25 ppm or higher. The presence of ballooned and hepatocytes became a regular feature of mid-zonal areas in ethanol treated rats and in the centrilobular areas of food deprived rats after exposure to </= 10 and </=25 ppm CC1(4) respectively. Necrotic hepatocytes were seen in centrilobular areas in liver from ethanol treated and food deprived rats when exposure CC1(4) was >/=25 ppm and >/=50 ppm respectively. These results indicate that consumption of ethanol and food deprivation potentiate CCl(4) induced hepatic damage even at low concentrations of CCl(4) by promoting lipid peroxidation. Thus heavy drinking may be a risk factor for CCl(4) induced hepatic damage even though the CCl(4) concentration is as low as the threshold limit value.