二乙氧基乙醇对大鼠脂、糖代谢的影响

目的探讨2-乙氧基乙醇(EE)染毒对大鼠某些脂代谢指标和血糖的影响及其可能机制.方法选取雄性Wistar大鼠,随机分为4组对照组、EE 200、400和800 mg/kg组.每天灌胃染毒1次,每周6次,持续6周.分别于每周后,将各组动物随机处死5只,对血液及肝脏中的脂代谢指标进行测定.结果从第3周开始,EE染毒大鼠血清甘油三酯(TG)含量(889.6±70.2)mg/L显著高于对照组(632.0±88.2)mg/L,血清极低密度脂蛋白(VLDL)含量(177.9±14.0)mg/L显著高于对照组(126.4±17.2)mg/L;肝脏脂肪酸β-氧化速度从第3周开始显著低于对照组;肝脏TG含量仅在染毒第5和6周,中、高剂量组显著高于对照组;血清含量从第4周开始,仅中或高剂量组显著降低;血清总胆固醇(TC)、高密度脂蛋白(HDL)和低密度脂蛋白(LDL)含量未发生显著性改变.结论EE长期染毒可对大鼠脂、糖代谢造成一定影响.     

全氟辛烷磺酸对SD大鼠肝毒性及其肝脏细胞色素P450 mRNA表达的影响

目的研究全氟辛烷磺酸盐(PFOS)染毒SD大鼠后,其对大鼠肝脏毒性及细胞色素P450(CYP450)亚型mRNA表达的影响。方法 40只SD雄性大鼠,随机分为5组:4个PFOS染毒组,染毒剂量分别为0.5、1.0、3.0和10.0mg/(kg.d),1个对照组。连续灌胃染毒28 d后,分析血清生化指标和观察肝脏病理变化,并检测肝脏CYP450各亚型mRNA的表达水平。结果与对照组相比,大鼠染毒PFOS 28 d后,各染毒组大鼠的体重明显降低,10.0 mg/kg染毒组大鼠的肝脏重量显著增加。各染毒组大鼠的血清谷丙转氨酶、胆汁酸等水平显著升高,三酰甘油、总胆固醇含量降低。病理检查发现,各染毒组大鼠的肝脏细胞出现浊肿、变性,甚至坏死。此外,3.0和10.0 mg/kg组大鼠肝脏的CYP1A2mRNA水平降低,而CYP17A1 mRNA水平升高。各染毒组CYP2B1 mRNA水平均升高,呈剂量效应关系。结论 PFOS的肝毒性呈剂量效应关系,并对CYP450的各个亚型有不同影响。     

辛硫磷对大鼠生殖内分泌系统的影响

目的 研究辛硫磷对雄性大鼠生殖内分泌系统的影响.方法 将每日不同剂量辛硫磷(5.9、29.4、147.0) mg/kg分别对雄性成年SD大鼠连续灌胃染毒15 d和30 d,应用RIA法测定血清卵泡刺激素(FSH)、黄体生成素(LH)、睾酮(T)和睾丸匀浆中睾酮(T)的水平,同步测定睾丸标志酶酸性磷酸酶(ACP)、γ-谷氨酰转移酶(γ-GT)的活性,并采用精子头计数法观测每日精子生成量(Spr)的变化.结果 与对照组比较,染毒大鼠15 d时,血清LH水平5.9 mg/kg,各染毒组表现为显著升高(P<0.05);血清FSH的水平随染毒剂量增加而升高,各染毒组均明显高于对照组(P<0.01);血清T水平随染毒剂量的增加呈现为升高的趋势,在147.0 mg/kg剂量组差异有统计学意义(P<0.05).染毒至30 d时,血清中LH水平在147.0 mg/kg剂量组差异有统计学意义(P<0.05);FSH在≤29.4 mg/kg剂量组表现有统计学意义(P<0.05).ACP各染毒组有统计学意义(P<0.01).γ-GT的活性在≥29.4 mg/kg剂量组范围均有明显差异(P<0.01).Spr与染毒剂量有明显的剂量依赖关系,在≥29.4 mg/kg剂量范围Spr显著减少(P<0.01).结论 辛硫磷对雄性大鼠有明显的生殖毒性,可影响其血清及睾丸性激素水平和酶活性,导致精子生成障碍.     

黄芪甲苷对甲基苯丙胺依赖大鼠脑组织中NO、SOD和MDA的影响

目的：探讨黄芪甲苷对甲基苯丙胺慢性染毒大鼠脑组织损伤的干预与保护作用。方法建立甲基苯丙胺（MA）慢性染毒大鼠实验动物模型,灌胃给予不同剂量的黄芪甲苷（10 mg/kg,20 mg/kg）,观察各组大鼠脑组织海马区和纹状体区一氧化氮（NO）、丙二醛（MDA）和超氧化物歧化酶（SOD）含量的变化及相互关系。结果 MA慢性染毒组脑组织海马区NO、MDA含量显著升高,SOD活力下降,与对照组比较,差异有统计学意义（P〈0.01）;黄芪甲苷大剂量组（20 mg/kg）与MA模型组相比,脑组织海马区NO、MDA含量降低,SOD活力升高,差异有统计学意义（P〈0.01）。结论黄芪甲苷能够降低MA慢性染毒大鼠脑组织海马区NO、MDA含量,升高SOD活力,并通过抗氧化作用对中枢神经系统的损伤有一定的干预与保护作用。     

二硫化碳对雄性大鼠性激素的影响及维生素E的拮抗作用

目的探讨二硫化碳(CS2)对雄性大鼠血清促卵泡生成激素(FSH)、促黄体生成素(LH)、绒毛膜促性腺激素(HCG)和睾酮(T)含量的影响,同时观察维生素E(VitaminE,VE)对其的拮抗作用。方法健康Wistar雄性大鼠36只随机分为6组,以不同浓度CS2(0、50、250和1250mg/m3)静式吸入染毒,共10周,另设CS2(1250mg/m3)﹢VE(250mg/kg)组和单纯VE(250mg/kg)组,VE拌入饲料中,染毒结束后,计算大鼠睾丸、附睾及垂体脏器系数,检测血清FSH、LH、HCG和T的含量。结果各染毒组睾丸脏器系数均低于对照组,高浓度组与对照组比较,差异有统计学意义(P<0.05)。高浓度组大鼠血清中LH和HCG含量下降,与对照组比较,差异有统计学意义(P<0.05)。中浓度组T含量升高,与对照组比较,差异有统计学意义(P<0.05)。VE干预后,LH和HCG含量均有不同程度的升高(P<0.05)。结论在本试验条件下,得出以下4点结论:(1)CS2染毒对雄性大鼠睾丸、附睾及垂体脏器系数均有一定程度的影响;(2)CS2亦能影响雄性大鼠血清激素FSH、LH、HCG、T的含量;(3)VE对C...     

氯沙坦对百草枯急性染毒大鼠血清细胞因子和氧化应激水平的影响

目的观察百草枯(paraquat,PQ)急性染毒大鼠血清细胞因子和氧化应激水平的变化,探讨氯沙坦对大鼠百草枯急性毒性的干预作用。方法选择成年SD大鼠32只,随机分为对照组(NS组)、百草枯(PQ组)以及氯沙坦干预7和14 d组。NS组每天灌胃生理盐水;PQ组为PQ 40 mg/kg一次性灌胃染毒,此后每天灌胃生理盐水;氯沙坦干预7 d组为PQ 40 mg/kg一次性灌胃染毒后,氯沙坦10 mg/(kg·d)连续灌胃给药7 d,此后7 d每天灌胃生理盐水;氯沙坦干预14 d组为PQ40 mg/kg一次性灌胃染毒后,氯沙坦10 mg/(kg·d)连续灌胃给药14 d。各组大鼠分别于第16天采集血样并分离血清,采用酶联免疫吸附法(ELISA)测定大鼠血清中IFN-γ、TNF-α、IL-8、IL-10的含量,用分光光度法测定血清中超氧化物歧化酶(T-SOD)和过氧化氢酶(CAT)活力以及羟自由基(HO·)含量。结果与对照组比较,PQ染毒后大鼠血清中IL-8含量升高(P0.05),而IL-10和IFN-γ的含量明显降低(P0.05)。血清中CAT活力和HO·含量升高(P0.05),T-SOD活力明显降低(P0.05)。氯沙坦干预7和14 d组IL-8和羟自由基含量、CAT活力以及氯沙坦14 d组仅IL-10和INF-γ含量基本恢复正常(P0.05);与PQ组比较,氯沙坦干预7和14 d组IL-8和HO·含量以及CAT活力均降低,而IL-10和INF-γ含量逐渐升高(P0.05)。TNF-α含量和T-SOD活力仅氯沙坦14 d组显著升高(P0.05)。结论氧化应激及炎症因子可能参与急性PQ中毒过程,且氯沙坦对PQ急性毒性具有一定的逆转作用。     

敦煌医方四时常服方对镉染毒大鼠肝脏指数、SOD、MDA和血清ALT的影响

目的研究敦煌医方四时常服方对镉染毒大鼠肝氧化损伤的影响。方法 60只SPF级Wistar大鼠随机分为6组:空白对照组、单纯镉染毒模型组、阳性药物对照组、氯化镉1.5 mg/kg·bw加敦煌四时常服方1.2 g/ml低剂量干预组、氯化镉1.5 mg/kg·bw加敦煌四时常服方2.4 g/ml中剂量干预组和氯化镉1.5 mg/kg·bw加敦煌四时常服方4.8 g/ml高剂量干预组。空白对照组腹腔注射生理盐水,单纯镉染毒模型组、阳性药物对照组、四时常服方低、中、高剂量干预组均腹腔注射0.1%氯化镉,1.5 mg/kg·bw注射,相当于1.5 ml/kg·bw,每周5次,共5周。模型组用蒸馏水、四时常服方组低、中、高剂量干预组分别用1.2、2.4和4.8 g/ml四时常服方灌胃,1次/d,连续5周,末次给药后股动脉采血,大鼠颈椎脱臼处死分离肝,称重,测定血清中丙氨酸转氨酶(ALT)、肝组织中超氧化物歧化酶(SOD)和丙二醛(MDA)的含量。结果与空白对照组比较,镉染毒模型组血清ALT含量明显上升(P0.01);与模型镉染毒组比较,四时常服方各干预组血清ALT含量下降,以高剂量干预组最为明显,差异有统计学意义(P0.01);与空白对照组比较,模型组大鼠肝组织中的SOD水平明显降低,MDA水平明显升高,肝脏指数明显升高差异有统计学意义(P0.01);与模型镉染毒组比较,各干预组大鼠肝组织的SOD、MDA水平差异均有统计学意义(P0.01)。结论在本实验条件下,敦煌医方四时常服方对镉染毒大鼠肝氧化损伤有一定的恢复作用。     

丙烯酰胺对大鼠谷氨酸和γ-氨基丁酸类神经递质含量的影响

目的探讨丙烯酰胺(ACR)染毒致大鼠大脑皮层和小脑谷氨酸(Glutamate,Glu)和γ-氨基丁酸(γ-aminobutyric acid,GABA)的含量变化。方法 60只雄性SD大鼠分为6组,即11 d试验组(生理盐水对照组、30 mg/kg ACR染毒组和50 mg/kg ACR染毒组)和21 d试验组(生理盐水对照组、15 mg/kg ACR染毒组和30 mg/kg ACR染毒组);步态评分评价神经行为改变;LC-MS/MS法测定染毒终点大脑皮层和小脑Glu和GABA含量变化。结果 11 d试验组在染毒终点时,50 mg/kg ACR染毒组与生理盐水对照组、30 mg/kg ACR染毒组相比,体重显著降低(P0.05),步态评分显著增高(P0.05);21d试验组在染毒终点时,30 mg/kg ACR染毒组与生理盐水对照组、15 mg/kg ACR染毒组相比,体重显著降低(P0.05),步态评分显著增高(P0.05);30 mg/kg 21 d和50 mg/kg 11 d染毒组与对照组相比,大脑皮层和小脑内兴奋性神经递质Glu含量显著降低(P0.05),且降低幅度一致。结论 ACR引起大鼠大脑皮层和小脑内兴奋性神经递质Glu含量的降低,可能是导致其神经毒性的致病机制之一。     

邻苯二甲酸二乙基己酯与双酚A混合染毒对大鼠睾丸损伤及与氧化应激关系研究

目的研究邻苯二甲酸二乙基己酯(DEHP)和双酚A(BPA)混合染毒对大鼠睾丸损伤作用及与氧化应激关系。方法将32只4周龄SD大鼠随机分为750 mg/kg·bw DEHP、100 mg/kg·bw BPA、750 mg/kg·bw DEHP+100 mg/kg·bw BPA和溶剂对照组,每组8只;用玉米油配制成相应浓度,以5 ml/kg·bw容积连续灌胃染毒6周,1次/d。观察大鼠睾丸脏器系数和组织病理改变、精子数目、血清睾酮(T)和雌二醇(E2)含量,检测睾丸组织丙二醛(MDA)、过氧化氢(H2O2)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)水平,以及氧化应激相关因子SOD、GSH-Px、核因子E2相关因子2(Nrf2)、血红素加氧合酶(HO-1)、γ-谷氨酸半胱氨酸合成酶(Gclc)和硫氧还蛋白还原酶(Txnrd)的基因表达。结果 DEHP组及混合剂量组睾丸脏器系数及3个剂量组精子数目明显低于对照组(P0.05),光学显微镜下可见曲细精管萎缩、生殖细胞大部分消失;混合剂量组血清T水平显著低于对照组(P0.05);混合剂量组MDA含量升高、SOD活性下降,DEHP组MDA含量和GSH-Px活性均升高,BPA组SOD活性降低,差异均具有统计学意义(P0.05);混合染毒组的SOD1基因表达降低、SOD3和GSH-Px升高,差异具有统计学意义(P0.05);混合染毒组Gclc、Txnrd和Nrf2表达低于对照组,DEHP组Txnrd表达也降低,而BPA组Txnrd、Nrf2表达均升高,差异均有统计学意义(P0.05)。结论 DEHP和BPA单独及混合染毒均能导致大鼠睾丸发育不良,生精细胞减少,精子总数下降;可诱导睾丸产生氧化应激,破坏体内抗氧化稳态失衡;DEHP和BPA混合染毒可导致更严重损害。     

2-乙氧基乙醇急性染毒大鼠睾丸和血清某些生化指标的变化

目的观察2-乙氧基乙醇(2-ethoxythanol,EE)急性染毒大鼠睾丸某些酶活力及血清和睾丸中铜、锌含量变化,探讨EE致睾丸损伤的可能机制.方法将90只大鼠随机分为对照组、EE800、1600和3200mg/kg4组,每组20只.将EE用蒸馏水配制成溶液,采取一次性灌胃染毒.于灌胃后第12、24、48和72h,将各组动物随机处死5只,测定睾丸非特异性酯酶、芳基酯酶(ARE)活力及Cu、Zn含量;测定血清Cu、Zn含量及睾丸/体比值.结果染毒后72h,EE800、1600和3200mg/kg组睾丸重量/体重比值分别为0.92、0.87、0.80%,明显低于对照组0.94%(P＜0.05);染毒后12h,EE800、1600和3200mg/kg组睾丸及血清Zn含量分别为21.76、16.96、19.80μmoL/g和1.37、1.35、1.29mg/L,显著低于对照组的33.08μmol/g和1.46mg/L(P＜0.05);在染毒后24h,EE800、1600和3200mg/kg组睾丸Cu和Zn含量分别为1.91、1.91、2.14和22.60、23.75、25.65μg/g,显著高于对照组的1.31和14.μg/g(P＜0.01).结论EE染毒大鼠睾丸重量/体重比值、ARE酶活力及血清Zn含量显著降低而睾丸Zn含量明显升高.推测睾丸可能是EE的靶器官,EE具有明显的睾丸毒性.     

Relationship between hepatotoxicity and induction of replicative DNA synthesis following single or multiple doses of carbon tetrachloride

The in vivo-in vitro DNA repair and DNA replication assay in mouse hepatocytes has promise as a short-term test for detecting potential mouse liver carcinogens. In addition, this assay may provide information on the mode of action of known hepatic carcinogens. The induction of DNA repair is clearly a response to hepatic DNA damage. However, it is unclear whether induction of replicative DNA synthesis (S phase) represents regenerative hyperplasia in response to hepatotoxicity or is a result of direct mitogenic stimulation of the hepatocytes by the test compound. The objective of the present study was to examine the relationship between hepatotoxicity, which was assessed by measuring serum concentrations of glutamic-oxalacetic transaminase (SGOT), glutamic-pyruvic transaminase (SGPT), alkaline phosphatase (AP), and gammaglutamyl transferase (GGT), and induction of S phase following either single or multiple doses of the model mouse hepatocarcinogen carbon tetrachloride (CCl4). Under the experimental conditions in this study, CCl4 elevated SGPT and SGOT but did not affect serum concentrations of AP or GGT. CCl4 did not induce DNA repair. An increase in the percentage of hepatocytes in S phase followed the appearance of elevated SGOT and SGPT in all single-dose studies. The results from the multiple-dose studies showed a similar relationship except that with 20 mg/kg X d the concentrations of SGOT and SGPT decayed to control values after 14 d of dosing whereas the percentage of hepatocytes in S phase remained markedly elevated (greater than 10 X control). The daily dose of CCl4 that gave a no-observed-effect level for induction of S phase was lower with multiple administrations than it was following a single exposure. A single administration of CCl4 at 25 mg/kg did not increase S phase, SGOT, or SGPT, but if 20 mg/kg X d was given for 7 d the number of hepatocytes in S phase and the concentrations of SGOT and SGPT increased more than 10-fold. These data support the hypothesis that induction of replicative DNA synthesis in the mouse liver following CCl4 administration is related to hepatotoxicity. In single-dose studies elevation in S phase was always associated with elevation of SGOT and SGPT. However, in the multidose studies, SGOT and SGPT declined after 14 d of administering 20 mg/kg X d while S phase remained elevated.(ABSTRACT TRUNCATED AT 400 WORDS)     

Hepatoprotective effect of Himoliv, a polyherbal formulation in rats

The effect of Himoliv (HV) was evaluated in carbon tetrachloride or paracetamol induced hepatotoxicity in rats. Liver necrosis was produced by administering single dose of either carbon tetrachloride (CCl4, 1 ml/kg, 50% v/v with olive oil, s.c.) or paracetamol (PC, 1 g/kg, p.o.). The liver damage was evidenced by elevated levels of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and serum alkaline phosphatase (ALP) and hepatic thiobarbituric acid reacting substances (TBARS) and superoxide dismutase (SOD). HV pretreatment (0.5 and 1.0 ml/kg, p.o.) significantly (P < 0.001) reduced CCl4 or PC-induced elevations of the levels of SGOT, SGPT, ALP and TBARS, while the reduced concentration of SOD due to CCl4 or PC was reversed. Silymarin (25 mg/ kg, p.o.), a known hepatoprotective drug showed similar results.     

Interaction of carbon tetrachloride with beta-naphthoflavone-mediated cytochrome P450 induction in winter flounder (Pseudopleuronectes americanus)

The interaction between beta-naphthoflavone induction (BNF: 100 mg/kg) and carbon tetrachloride (CCl4; 1 ml/kg) hepatotoxicity was examined in the flounder. Treatment groups composed of control, BNF, CCl4, and BNF/CCl4 were compared in terms of cytochrome P450 isozyme content (LM4b; LM2), catalytic activity, isozyme distribution. SGOT-SGPT levels, and pathology. CCl4 administration resulted in significant reductions in both the constitutive P450 (LM2) and the BNF-inducible isozyme (LM4b) as well as elevations in SGPT and SGOT levels. The decline in LM4b isozyme content was reflected by stoichiometric decreases in ethoxyresorufin-O-deethylase activities. BNF/CCl4 coadministration was protective in part against CCl4 hepatotoxicity. Immunohistochemistry indicated that LM4b was diffusely distributed throughout the liver. These interactions have demonstrated a multiple P450 isozyme involvement, the protective nature of BNF against CCl4 hepatotoxicity in the flounder, the ability to maintain an inductive response in face of CCl4 coadministration, and the diffuse distributional pattern of LM4b in the flounder liver.     

Hepatoprotective and immunomodulatory properties of Tinospora cordifolia in CCl4 intoxicated mature albino rats

Effect of Tinospora cordifolia extract on modulation of hepatoprotective and immunostimulatory functions in carbon tetrachloride (CCl4) intoxicated mature rats is reported here. Administration of CCl4 (0.7 ml/kg body weight for 7 days) produces damage in the liver as evident by estimation of enzymes such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transminase (SGPT) and alkaline phosphatase (ALP) as well as serum bilirubin level. CCl4 administration also causes immunosuppressive effects as indicated by phagocytic capacity, chemotactic migration and cell adhesiveness of rat peritoneal macrophages. However, treatment with T. cordifolia extract (100 mg/kg body weight for 15 days) in CCl4 intoxicated rats was found to protect the liver, as indicated by enzyme level in serum. A significant reduction in serum levels of SGOT, SGPT, ALP, bilirubin were observed following T. cordifolia treatment during CCl4 intoxication. Treatment with T. cordifolia extract also deleted the immunosuppressive effect of CCl4, since a significant increment in the functional capacities of rat peritoneal macrophages (PM phi) was observed following T. cordifolia treatment. The results of our experiment suggest that treatment by T. cordifolia extract may be the critical remedy for the adverse effect of CCl4 in liver function as well as immune functions.     

Effect of endrin and endrin derivatives on hepatobiliary function and carbon tetrachloride-induced hepatotoxicity in male and female rats

The effects of the cyclodiene pesticide, endrin, and its aldehyde and ketone metabolites on hepatobiliary function and CCl4-induced hepatotoxicity were investigated in Sprague-Dawley rats. The rats were given control diet or diets containing 5 or 10 ppm endrin, 10 ppm endrin aldehyde or 5 ppm endrin ketone for 15 days. Three to six rats from each treatment group were given a single ip dose (100 microliter/kg body weight) of CCl4 in corn oil (1 ml/kg) on day 15. Levels of serum glutamic-oxalacetic transaminase (SGOT), glutamic-pyruvic transaminase (SGPT), isocitrate dehydrogenase and ornithine-carbamyl transferase, bile flow and biliary excretion of an anionic model compound, phenolphthalein glucuronide (PG), were measured on day 16. Dietary treatment with endrin at either dose level did not significantly elevate serum enzyme levels, while endrin aldehyde produced a slight increase in SGOT and SGPT and endrin ketone produced a small elevation in SGPT levels. Treatment with endrin aldehyde or endrin ketone did not result in significant alterations of bile flow or biliary PG excretion. Treatment with 5 ppm endrin produced a significant reduction in bile flow and a corresponding reduction in PG excretion by male rats, whereas treatment with 10 ppm endrin reduced only the PG excretion by male rats. Female rats treated with 5 or 10 ppm endrin showed a dose-dependent choleretic effect with a commensurate increase in PG excretion. With the exception of a further slight reduction in PG excretion by male rats, treatment with the endrin or endrin derivative did not potentiate CCl4-induced alterations in hepatobiliary functions. Although the levels of some serum enzymes of rats given endrin or endrin derivatives plus CCl4 were elevated over those of rats given CCl4 alone, the increases were not of the magnitude of those that have been reported previously for chlordecone. Generally, female rats challenged with CCl4 or endrin/CCl4 exhibited greater increases in serum enzyme levels than did male rats given corresponding treatments.     

金针菇提取物的保肝及抗肿瘤作用

目的研究金针菇提取物 (FVE)对小鼠急性肝损伤转氨酶活性的影响及其抗肿瘤能力。方法用四氯化碳 (CCl4)和D 氨基半乳糖 (D Gal)分别建立小鼠急性肝损伤模型 ,以FVE和阳性对照药云芝多糖灌胃治疗 ,分别测定血清中谷丙转氨酶 (SGPT)、谷草转氨酶 (SGOT)活性。小鼠接种Heps ,测定抑瘤率并观察荷瘤小鼠的存活天数。结果FVE 0 .8g kg对CCl4和D Gal造成的小鼠急性肝损伤SGPT、SGOT活性升高有显著的降低作用 ,与模型对照组相比 ,P <0 .0 1。FVE ,灌胃 0 .8g kg ,1 0d ,可显著抑制小鼠Heps肿瘤的生长并明显延长Heps腹水型小鼠的存活天数。结论FVE对肝脏损伤有保护作用 ,并对Heps肿瘤有抑制作用     

Potentiation of carbon tetrachloride hepatotoxicity in rats by pretreatment with polychlorinated biphenyls.

Pretreatment of male rats with Aroclor 1254 at a dose of 25 mg/kg i.p. for 6 days resulted in potentiation of the hepatotoxicity of inhaled carbon tetrachloride (CCl4) as evidenced by a decrease in liver glucose-6-phosphatase and elevations of serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), isocitrate dehydrogenase, and sorbitol dehydrogenase. Aroclor 1254 alone did not demonstrate hepatotoxicity. Aroclor 1254 administration resulted in large increases in cytochrome c reductase, cytochrome P-450 (448) AND P-Nitroanisole demethylation. Subsequent exposure to CCl4 vapor resulted in over 70% decreases in the latter two parameters. The potentiation was dose-dependent with a dose of 5 mg/kg or higher being effective. Aroclor 1260 administration gave results similar to those of Aroclor 1254, but Aroclor 1221 enhanced CCl4 toxicity to a lesser extent.     

Mechanism for the protective effects of silymarin against carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice. Evidence that silymarin acts both as an inhibitor of metabolic activation and as a chain-breaking antioxidant

Administration of silymarin (800 mg/kg i.p.) 30 min before carbon tetrachloride (18 microL/kg i.p.) did not modify total hepatic levels of CCl4 and metabolites in mice, but decreased by 40% the in vivo covalent binding of CCl4 metabolites to hepatic lipids at 2 hr. This pretreatment decreased by 60% the exhalation of ethane during the first hour after CCl4, and decreased by 50% the incidence of liver cell necrosis. In vitro, silymarin (800 micrograms/mL) decreased by 50 to 70% various monooxygenase activities, and decreased by 20% the covalent binding of CCl4 metabolites to microsomal proteins. Silymarin (800 micrograms/mL) decreased by 70% in vitro lipid peroxidation mediated by CCl4 metabolites, and decreased by 90% peroxidation mediated by NADPH alone. Silibinin, one of the three isomers composing silymarin, also decreased carbon tetrachloride-induced lipid peroxidation; this effect, however, was less than that of silymarin in vitro, and was more transient in vivo. Pretreatment with silibinin (800 mg/kg i.p.) 30 min before CCl4 (18 microL/kg i.p.) did not improve SGPT activity or liver histology at 24 hr. We conclude that silymarin prevents carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice, firstly, by decreasing the metabolic activation of CCl4, and, secondly, by acting as a chain-breaking antioxidant.     

Protective effect of Mentha piperita against arsenic-induced toxicity in liver of Swiss albino mice

The protective role of leaves of Mentha piperita Linn (Mint) was studied in adult Swiss albino mice against arsenic-induced hepatopathy. The animals were divided into four groups. Group I: only vehicle (0.9% NaCl) was administered. Group II: the animals received Mentha leaf extract (1 g/kg body weight per day) orally for 30 days. Group III: animals were treated with sodium arsenite (4 mg/kg body weight) intraperitoneally in 0.9% NaCl. Group IV: animals were given Mentha extract for 10 consecutive days prior to sodium arsenite treatment and continuously for 30 days after sodium arsenite treatment. The animals from the above groups were killed at various time-points, and body weight and liver weight were measured. The biochemical estimation of lipid peroxidation (LPO), reduced glutathione (GSH), lactate dehydrogenase (LDH), acid phosphatase (ACP), and alkaline phosphatase (ALP) in liver and serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) in serum were done. In the arsenic-treated group there was a significant increase in ACP, ALP, SGOT, SGPT and LPO content, whereas a significant decrease was recorded in body weight, liver weight, GSH and LDH activity in liver. Pre- and post-treatment of Mentha with arsenic significantly alters the biochemical parameters in liver. A significant decline in ACP, ALP, SGOT, SGPT and LPO content was observed. However, a significant increase in body weight, liver weight, GSH content and LDH activity in liver was estimated. The results indicate that the Mentha extract may be useful in reducing the side effects of arsenic-induced hepatopathy.     

Role of an Ethanolic Extract of Crotalaria juncea L. on High-Fat Diet-Induced Hypercholesterolemia

Objective

To evaluate the antihypercholesterolemic effects of 50 mg/kg BW and 100 mg/kg BW per day of an ethanolic extract of Crotalaria juncea Linn (whole plant) by performing in vivo studies.

Methods

The effects of oral administration of 50 mg/kg BW and 100 mg/kg BW per day of an ethanolic extract of Crotalaria juncea Linn (whole plant) in rats fed with a high-fat diet were investigated by evaluating parameters like food consumption, weight gain, fecal fat excretion, serum and liver lipids, and biochemical profiles as well as by histopathological studies. The results were compared to animals fed with the standard diet and animals fed with a high-fat diet and atorvastatin (10 mg/kg BW).

Results

The animal group administered with the ethanolic extract for 35 days showed decreased levels of TC, LDL, VLDL, TG, HDL+VLDL, VLDL+LDL, LDL/TC, AI, SGOT, SGPT, and elevated levels of HDL, HDL/TC, significantly (p<0.01 & p<0.05) in a dose-dependent manner. The evaluation of liver tissues of the animal groups treated with the herbal extract and standard had shown increased levels of SOD, GSH, and catalase, whereas levels of SGOT, SGPT, total glucose, HMG-CoA, lipase, amylase, and the percentage of malon-dialdehyde were decreased when compared with the high-fat diet-fed rats. Body weight and food intake in the treated groups were significantly lower than that in the model control.

Conclusion

The present study showed that an ethanolic extract of Crotalaria juncea L. influences several blood lipid and metabolic parameters in rats, suggesting a potential benefit as an antihypercholesterolemic agent.