基于氧化应激研究苦豆子不同提取物的肝毒性机制

基于亚急性毒性实验对苦豆子不同提取物肝毒性机制进行研究,为苦豆子临床安全使用提供理论依据。分别采用75%乙醇回流法(ER)、水煎煮法(WD)、75%乙醇超声法(EU)和水超声法(WU)制备苦豆子提取物,通过不同提取物的亚急性毒性实验测定大鼠肝组织中谷丙转氨酶(ALT)、谷草转氨酶(AST)、超氧化物歧化酶(SOD)、谷胱甘肽酶(GSH)、丙二醛(MDA)水平以评价其肝毒性;应用免疫组织化学和蛋白免疫印迹方法测定氧化应激相关蛋白红系衍生的核因子2相关因子(Nrf2)、血红素氧合酶1(HO-1)、超氧化物歧化酶1(SOD1)、超氧化物歧化酶2(SOD2)表达,进一步探讨其肝毒性机制。结果显示,与空白组相比,AST在雄性大鼠各给药组血清中显著性升高,ALT在雌雄大鼠血清中均呈升高趋势,尤其在雄性WD、ER组、雌性WD、WU、EU组中有显著性差异。与空白组比较,雄性给药大鼠肝脏SOD和GSH在各组中均显著性降低,GSH在雌性大鼠肝组织中呈升高趋势,其中WD组有显著性差异,MDA在雌、雄给药大鼠肝脏中均显著升高。给药后,对Nrf2/HO-1氧化应激通路中相关蛋白检测后发现,Nrf2蛋白相较空白组在肝组织中表达均呈降低趋势,其中雄性WD、WU、EU组和雌性WD、EU、ER组最为显著,HO-1在雌雄各组肝组织表达中均发生显著性降低。SOD1在雌性各组中均有显著性降低,而在雄性中WD和ER组有显著性降低。本研究发现苦豆子不同提取物对大鼠肝脏都有一定的毒性,其毒性机制主要是通过调控Nrf2/HO-1通路中相关蛋白造成机体氧化应激而发生。     

基于抗炎及抗氧化作用探讨微生态制剂在非酒精性脂肪肝模型大鼠中的应用价值

目的研究基于抗炎及抗氧化作用探讨微生态制剂在非酒精性脂肪肝(NAFLD)模型大鼠中的应用价值。方法选择成年雄性SD大鼠并随机分为对照组、NAFLD组、蓝莓益生菌(BP)组。后2组采用复合高脂饲料建立NAFLD模型,BP组给予蓝莓联合益生菌干预。比较3组间血清肝功能指标、炎症指标、氧化应激指标含量及肝脏组织中炎症及氧化应激信号分子表达的差异。结果 NAFLD组大鼠血清中ALT、AST、TNF-α、IL-1、IL-6、IL-18、MDA的含量及肝脏中p-p38MAPK、NF-κB的表达量明显高于对照组,血清中SOD、GPX的含量及肝脏中p-AMPK、Nrf-2的表达量明显低于对照组;BP组大鼠血清中ALT、AST、TNF-α、IL-1、IL-6、IL-18、MDA的含量及肝脏中p-p38MAPK、NF-κB的表达量明显低于NALFD组,血清中SOD、GPX的含量及肝脏中p-AMPK、Nrf-2的表达量明显高于NALFD组。结论蓝莓益生菌用于NALFD模型大鼠的干预能够改善肝功能并抑制炎症反应、氧化应激反应。     

茶多酚对NASH 大鼠肝脏组织VEGF 及氧化应激的影响

目的:茶多酚对NASH大鼠肝脏组织VEGF及氧化应激的影响。方法:雄性SD大鼠30只,随机分为3组,正常对照组、模型组、茶多酚治疗组。正常组普通饲料喂养,模型组喂高脂饮食,茶多酚治疗组在高脂饮食12周后茶多酚(150mg(/kg.d)灌胃治疗,16周末处死各组大鼠,留取肝脏组织,观察各组大鼠肝组织病理改变,测定其肝脏丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性以及血管内皮生长因子(VEGF)、Ⅰ、Ⅲ型胶原的表达。结果:模型组大鼠肝组织中SOD活性降低而MDA含量以及VEGF、Ⅰ、Ⅲ型胶原表达均明显高于正常组。茶多酚治疗可减轻肝纤维化程度,显著升高肝组织中SOD活性、降低MDA含量以及VEGF、Ⅰ、Ⅲ型胶原表达水平。结论:茶多酚可通过抑制肝纤维化组织VEGF表达,降低肝组织氧化应激水平而发挥抗肝纤维化作用。     

咖啡酸对慢性铝负荷大鼠肝损伤的保护作用

目的观察5-脂氧酶(5-LO)抑制剂咖啡酸对慢性铝负荷所致大鼠肝损伤的保护作用,并初步探讨其可能的机制。方法将SD大鼠分为空白对照组、慢性铝负荷模型组、咖啡酸低剂量组和咖啡酸高剂量组,除空白对照组外,每组大鼠每天灌胃给予葡萄糖酸铝(Al3+200 mg·kg-1·d-1),给药组大鼠在给铝后1周分别灌胃给予2个剂量的咖啡酸,每周5 d,连续20周。建模完成后,用生化法检测大鼠血清中丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST)和碱性磷酸酶(ALP)活性,以及肝组织丙二醛(MDA)含量,超氧化物歧化酶(SOD)活性,采用苏木精-伊红染色法观察大鼠肝脏组织形态学变化,用免疫组织化学法检测大鼠肝组织5-LO蛋白表达情况。结果与空白对照组大鼠比较,慢性铝负荷模型组大鼠血清ALT、AST、ALP活性显著升高,肝组织MDA含量显著增加,SOD活性显著下降,肝细胞出现明显空泡性变、点状坏死、肝细胞排列紊乱,肝组织5-LO在血管周围肝细胞胞浆中表达明显。与铝负荷模型组比较,给予咖啡酸后大鼠肝细胞损伤减轻,血清ALT、AST、ALP活性明显降低,肝组织MDA含量显著减少,SOD活性显著上升,肝组织5-LO表达明显减少。结论咖啡酸能减轻慢性铝负荷所致肝损伤,机制可能与其抑制5-LO表达、减轻氧化应激反应损伤有关。     

七味净肝灵对酒精性肝损伤大鼠的保护作用研究

探讨七味净肝灵(QWJGL)对酒精性肝损伤大鼠的保护作用及作用机制。将60只大鼠随机分为正常组、模型组、水飞蓟宾组(0.18 g/kg)、QWJGL高、中、低剂量组(8、4、2 g/kg),每组10只。造模采用灌胃56%vol白酒(10 mL/kg),2 h后,各用药组灌胃给药,持续给药30天。末次给药16 h后,取血,收集肝脏、脾脏和胰腺,计算LI、SI和TI,生化法测定血清ALT、AST、MDA、SOD和GSH-Px含量,ELISA法检测肝脏中IL~(-1)β、IL-6和TNF-α含量,Western blot检测肝组织NF-κB和CD14表达,HE染色观察肝脏组织病理学变化。结果表明,QWJGL可降低酒精性肝损伤大鼠的LI(P0.05),提高SI和TI(P0.05),降低肝损伤大鼠血清中ALT和AST活性(P0.05),并且可以降低MDA含量(P0.05),增强SOD和GSH-Px活性(P0.05),降低TNF-α、IL~(-1)β和IL-6水平(P0.05),抑制肝组织NF-κB和CD14表达(P0.05)。综上,QWJGL对酒精性肝损伤有明显的保护作用,其保肝作用可能与抑制氧化应激、炎症反应和调控CD14、NF-κB蛋白表达有关。     

伤寒头对CCl_4致小鼠急性肝损伤的保护作用及其机理

本研究将健康昆明种小鼠36只,雌雄各半,随机分为空白对照组、模型组、药物联苯组、伤寒头高剂量、中剂量及低剂量组。各分组连续给药3d,末次给药1h后,除正常对照组外,其余各组腹腔注射1%CCl4花生油溶液0.1mL/10g建立小鼠急性肝损伤模型。测试小鼠禁食24h后,摘眼球取血并处死动物,分离血清进行血清生化指标的测定,检测小鼠血清中门冬氨酸氨基转氨酶(AST)、丙氨酸氨基转氨酶(ALT)、白蛋白(ALB)和总蛋白(TP)水平;剖检并取肝脏组织测肝脏重量,取部分肝组织研磨成匀浆测定超氧化物歧化酶(SOD),丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-PX)。观察伤寒头处理下小鼠血清中AST、ALT、ALB和TP以及肝脏中SOD、MDA和GSH-PX的变化。结果表明,各伤寒头治疗组对AST、ALT均有明显的降低作用(P0.01),对TP、ALB没有影响(P0.05);各伤寒头治疗组对SOD和GSH-PX有升高作用(P0.05),对MDA有降低作用(P0.05),对肝脏指数没有影响(P0.05)。根据本研究结果,我们推断伤寒头对四氯化碳所致小鼠急性肝损伤具有明显的保护作用,主要是通过提高SOD和GSH-PX酶的活性,降低MDA来达到保护肝脏的作用。     

局部热应激预处理对肝脏缺血/再灌注损伤的防护作用的机制

目的:探讨热应激预处理诱导产生的热休克蛋白70对肝脏缺血/再灌注损伤的保护作用的机制.方法:应用pringle,s法制备肝脏缺血/再灌注损伤模型及热应激预处理模型.将实验大鼠随机分为热应激预处理(HP I/R)组与非预处理(I/R)组,对比观察两组动物肝脏缺血/再灌注后0、4、8、12、24 h时肝脏HSP70的表达、SOD活力和MDA的产生量及大鼠血清门冬氨酸转氨酶(aspartate transaminase,AST),丙氨酸转氨酶(alanine transaminase,ALT)的活性与肝脏病理组织学改变.结果:热应激预处理组各时间点肝脏HSP70的表达及SOD的活力均比非预处理组同一时间点高,而血清AST、ALT酶活性及MDA的产生量较非预处理组低,病理损伤也比非预处理组减轻.结论:热应激预处理诱导产生的热休克蛋白70可能通过促进SOD的产生,从而降低氧自由基对肝脏的损害,起到保护肝脏缺血/再灌注损伤的作用.     

中药脂肝宁预防酒精性脂肪肝的实验研究

目的探讨中药脂肝宁预防酒精性脂肪肝的作用机理。方法应用酒精灌胃方法建立大鼠酒精性脂肪肝模型,造模同时给予中药脂肝宁(ZGN)药物干预,以硫普罗宁(TPN)为对照,检测血清肝功能和肝匀浆甘油三酯(TG)、氧自由基(ORF)、抗超氧阴离子(ASOA)、超氧化物歧化酶(SOD)及丙二醛(MDA)含量,并对大鼠肝脏行病理学检查。结果酒精灌胃12周后大鼠形成酒精性脂肪肝,中药脂肝宁高浓度组血清门冬氨酸氨基转移酶(AST)和肝匀浆TG、ORF及MDA含量显著降低,而ASOA和SOD含量升高(P<0.05),肝脏脂肪变明显改善。结论中药脂肝宁通过抑制氧化应激、稳定肝细胞膜、抑制脂质过氧化来改善酒精所致肝细胞脂肪变性。     

多烯磷脂酰胆碱对肝癌大鼠肝细胞保护作用的研究

探讨多烯磷脂酰胆碱(PPC)对肝癌大鼠肝脏细胞的保护作用.将72只Wistar大鼠随机分为正常对照组、肝癌模型组、联苯双酯阳性对照组、PPC低、中、高剂量组6组,模型组、阳性对照组及PPC低、中、高剂量组均采用二乙基亚硝胺(DEN)诱导构建肝癌大鼠模型,低、中、高剂量PPC组在模型组的基础上分别给予100、200、300 mg·(kg·d)-1ppC灌胃,治疗6周后,腹主动脉取血测定血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)以及总胆红素(TBIL)含量,然后处死大鼠,测定肝脏湿重,计算肝脏指数,同时测定肝匀浆中丙二醛(MDA),超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平.结果显示,与正常对照组相比,DEN诱导的肝癌模型组中肝脏指数、AST、ALT、TBIL、MDA水平显著升高(p＜0.01);SOD、GSH-Px活力则显著下降(p＜0.01).PPC和联苯双酯能依耐性的逆转DEN所致的上述改变,表现为肝脏指数、AST、ALT、TBIL、MDA显著降低,SOD、GSH-Px活力则显著上升,PPC高剂量组作用最为明显,随着PPC摄入量的增加,PPC对肝癌大鼠肝细胞的保护作用也相应增强.     

睡眠剥夺小鼠肝脏中肿瘤坏死因子α表达上调

目的探讨睡眠剥夺(sleep deprivation,SD)对小鼠肝脏形态、功能的影响及肿瘤坏死因子α(tumor necrosis factor,TNF-α)表达的意义。方法 C57雄性小鼠随机分为正常对照组、睡眠剥夺24h、48h和72h组,全自动生化分析仪检测血清中谷丙转氨酶(alanine aminotransferase,ALT),谷草转氨酶(aspartate aminotransferase,AST)的活性,硫代巴比妥酸法检测肝组织丙二醛(malonaldehyde,MDA)含量,黄嘌呤氧化酶法检测肝组织超氧化物歧化酶(superoxidedismutase,SOD)活性;采用HE染色检测肝组织学特征,免疫组织化学染色和Western blot检测肝组织TNF-α表达水平。结果随睡眠剥夺时间延长肝脏组织中,SOD表达量下降,MDA表达量增加;ALT、AST水平在睡眠剥夺24h后显著增高,48h、72h表达水平持续增高;HE染色可见睡眠剥夺组小鼠出现肝细胞肿胀、排列不规则、肝小叶结构破坏、Kupffer细胞增生、大量炎症细胞浸润;免疫组织化学及免疫印迹显示,睡眠剥夺组小鼠肝脏中TNF-α的表达随睡眠剥夺时间的延长而表达持续增加。结论睡眠剥夺后肝细胞过氧化脂质作用诱发氧化应激导致小鼠肝脏形态和功能受损,活化TNF-α,诱发炎症反应,加重对肝脏的损害。     

紫檀芪调节Keap-1/Nrf2/HO-1信号通路对非酒精性脂肪肝大鼠氧化应激和细胞凋亡的影响

摘要 目的：研究紫檀芪调节Kelch样ECH关联蛋白1（Keap-1）/核因子E2相关因子2（Nrf2）/血红素加氧酶-1（HO-1）信号通路对非酒精性脂肪肝（NAFLD）大鼠氧化应激和细胞凋亡的影响。方法：将60只SD大鼠随机分为对照组、模型组、紫檀芪低剂量组（30 mg/kg）、紫檀芪高剂量组（60 mg/kg）、紫檀芪（60 mg/kg）+N-（4-（2,3-二氢-1-（2''-甲基苯甲酰）-1H-吲哚-5-基）-5-甲基-2-噻唑基）-1,3-苯并二氧唑-5-乙酰胺（ML385）（30 mg/kg）组，每组12只。模型组与药物干预组大鼠以高脂饲料饲养诱导NAFLD模型，对照组大鼠以普通饲料饲养，各组连续喂养12周。以紫檀芪和ML385分组处理14 d后（对照组以等剂量生理盐水处理），检测各组大鼠脂代谢指标[三酰甘油（TG）、总胆固醇（TC）及游离脂肪酸（FFA）水平]、肝指数、肝功能指标[谷丙转氨酶（ALT）及谷草转氨酶（AST）]水平、血清白细胞介素（IL）-17、IL-6、IL-10、氧化应激指标[丙二醛（MDA）、超氧化物歧化酶（SOD）及过氧化氢酶（CAT）]水平；原位末端标记法（TUNEL）染色检测各组大鼠肝细胞凋亡率；蛋白免疫印迹法检测各组大鼠肝组织凋亡相关蛋白及Keap-1/Nrf2/HO-1通路相关蛋白表达。结果：与对照组相比，模型组大鼠血清IL-10、SOD及CAT水平、肝组织Nrf2、HO-1、Bcl-2表达水平显著降低（P＜0.05），TG、TC及FFA水平、肝指数、ALT及AST水平、血清IL-17、IL-6、MDA水平、肝细胞凋亡率、肝组织Keap-1及Bax表达水平显著升高（P＜0.05）。与模型组相比，紫檀芪低、高剂量组大鼠血清IL-10、SOD及CAT水平、肝组织Nrf2、HO-1、Bcl-2表达水平均升高（P＜0.05），TG、TC及FFA水平、肝指数、ALT及AST水平、血清IL-17、IL-6、MDA水平、肝细胞凋亡率、肝组织Keap-1、Bax表达水平均降低（P＜0.05）；与紫檀芪低剂量组相比，紫檀芪高剂量组大鼠血清IL-10、SOD及CAT水平、肝组织Nrf2、HO-1、Bcl-2表达水平升高（P＜0.05），TG、TC及FFA水平、肝指数、ALT及AST水平、血清IL-17、IL-6、MDA水平、肝细胞凋亡率、肝组织Keap-1及Bax表达水平降低（P＜0.05）；与紫檀芪高剂量组相比，紫檀芪+ML385组大鼠血清IL-10、SOD及CAT水平、肝组织Nrf2、HO-1、Bcl-2表达水平降低（P＜0.05），TG、TC及FFA水平、肝指数、ALT及AST水平、血清IL-17、IL-6、MDA水平、肝细胞凋亡率、肝组织Bax表达水平升高（P＜0.05）。结论：紫檀芪可能通过激活Keap-1/Nrf2/HO-1信号通路，改善NAFLD大鼠脂代谢水平，调节炎症反应及氧化应激，减轻肝组织脂肪变性及细胞凋亡。     

Carnosine and taurine treatments decreased oxidative stress and tissue damage induced by d-galactose in rat liver

d-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of carnosine (CAR) or taurine (TAU), having antioxidant effects, on hepatic injury and oxidative stress in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days/week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days/week) or TAU (2.5 % w/w; in rat chow) for 2 months. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and hepatic malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-0050x), and glutathione transferase (GST) activities were determined. Hepatic expressions of B cell lymphoma-2 (Bcl-2), Bax and Ki-67 were evaluated. Serum ALT, AST, hepatic MDA, and PC levels were observed to increase in GAL-treated rats. Hepatic Bax expression, but not Bcl-2, increased, Ki-67 expression decreased. GAL treatment caused decreases in GSH levels, SOD and GSH-Px activities in the liver. Hepatic mRNA expressions of SOD, but not GSH-Px, also diminished. CAR or TAU treatments caused significant decreases in serum ALT and AST activities. These treatments decreased apoptosis and increased proliferation and ameliorated histopathological findings in the livers of GAL-treated rats. Both CAR and TAU reduced MDA and PC levels and elevated GSH levels, SOD and GSH-Px (non significant in TAU?+?GAL group) activities. These treatments did not alter hepatic mRNA expressions of SOD and GSH-Px enzymes. Our results indicate that CAR and TAU restored liver prooxidant status together with histopathological amelioration in GAL-induced liver damage.     

小茴香对肝纤维化大鼠脂质过氧化水平的影响

目的：研究小茴香对肝纤维化大鼠的脂质过氧化水平的影响。方法：取Wister大鼠100只,随机取12只设为正常组,其余采用四氯化碳（CCL4）复合因素法复制肝纤维化大鼠模型,复制成功后随机分为模型对照组、小茴香组和复方丹参组（n=12）;相应药物干预8周后,镜检肝组织形态学改变;全自动生化分析仪检测外周血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）水平与血清总蛋白（TP）、白蛋白（ALB）含量;生化法检测肝组织羟脯氨酸（HYP）与血清丙二醛（MDA）含量及超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—PX）、过氧化氢酶（CAT）活性。结果：HE结果显示：模型组肝脏炎症与脂肪变性明显,经小茴香干预后明显改善。生化检测结果显示：与正常组比较,模型组ALT、AST水平显著升高（P〈0．05）,TP、ALB含量显著降低（P〈O．05）,HYP、MDA含量显著增加（P〈0．05）,而SOD、GSH—PX和CAT活性显著降低（P〈0．05）;与模型组比较,小茴香组ALT、AST水平显著下降（P〈0．05）,TP、ALB水平显著升高（P〈0．05）;HYP、MDA含量显著降低（P〈0．05）,SOD、GSH—PX和CAT活性显著提高（P〈0．05）。结论：小茴香的抗肝纤维化作用可能与调节大鼠脂质过氧化水平有关。     

腹腔镜胆囊切除术对急性化脓性胆囊炎患者血清SOD,MDA及肝功能的影响

目的:探讨腹腔镜胆囊切除术治疗急性化脓性胆囊炎的疗效及对患者血清超氧化物歧化酶(SOD)、丙二醛(MDA)及肝功能的影响。方法:选择2014年9月至2016年9月我院接诊的92例急性化脓性胆囊炎患者,随机分为观察组(n=46)和对照组(n=46),对照组使用传统开腹式胆囊切除术,观察组使用腹腔镜下胆囊切除术。观察并比较两组患者的术中出血量、术后引流量、手术时间、术后排气时间及住院时间,治疗前后丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、超氧化物歧化酶(SOD)及丙二醛(MDA)水平,以及术后并发症的发生情况。结果:观察组术中出血量、术后引流量少于对照组,手术时间、术后排气时间、排便时间、住院时间均比对照组短(P0.05);手术后,观察组丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBIL)水平均比对照组低(P0.05);观察组超氧化物歧化酶(SOD)水平高于对照组,丙二醛(MDA)水平低于对照组(P0.05);观察组术后并发症总发生率低于对照组(P0.05)。结论:腹腔镜胆囊切除术治疗急性化脓性胆囊炎的效果显著,对患者肝功能损伤较小,术后并发症少,值得临床应用推广。     

探究壮方柔肝化纤颗粒对肝纤维化大鼠肝组织病理影响机制

摘要 目的：探究壮方柔肝化纤颗粒对肝纤维化大鼠肝组织病理影响机制。方法：选取80只雄性Wistar大鼠随机将其平均分成正常对照组、病理模型组、柔肝化纤颗粒低、中、高剂量组,每组各16只。四氯化碳复合因素造模,观察记录大鼠肝脏形态,采用HE染色、Masson染色观察大鼠肝组织和胶原纤维变化,检测血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）指标数值,分析大鼠肝组织中谷胱甘肽过氧化物酶（GSH-Px）、羟脯氨酸（HYP）、超氧化物歧化酶（SOD）与丙二醛（MDA）的含量。结果：柔肝化纤颗粒低、中、高剂量组大鼠肝细胞变性、坏死及纤维化组织增生程度均较病理模型组明显减轻。柔肝化纤颗粒低、中、高剂量组血清ALT、AST指标数值与肝组织中HYP、MDA指标水平较病理模型组呈现剂量依赖性降低（P＜0.001）,而柔肝化纤颗粒高剂量组GSH-Px、SOD的指标含量显著高于病理模型组,差异均有统计学意义（P＜0.001）。结论：柔肝化纤颗粒可有效改善肝纤维化大鼠的肝细胞损害情况,减轻其肝组织炎症程度,对肝纤维化大鼠有一定的保肝护肝与抗肝纤维化作用,其机制可能与提高GSH-Px与SOD的水平、降低HYP与MDA的含量、降低氧化应激水平、调节脂质代谢、减少机体胶原蛋白合成等相关。     

Silymarin modulates Cisplatin-induced oxidative stress and hepatotoxicity in rats

Cisplatin (CDDP) is a widely used anticancer drug, but at high dose, it can produce undesirable side effects such as hepatotoxicity. Because silymrin has been used to treat liver disorders, the protective effect of silymarin on CDDP-induced hepatotoxicity was evaluated in rats. Hepatotoxicity was determined by changes in serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST], nitric oxide [NO] levels, albumin and calcium levels, and superoxide dismutase [SOD], glutathione peroxidase [GSHPx] activities, glutathione content, malondialdehyde [MDA] and nitric oxide [NO] levels in liver tissue of rats. Male albino rats were divided into four groups, 10 rats in each. In the control group, rats were injected i.p. with 0.2 ml of propylene glycol in saline 75/25 (v/v) for 5 consecutive days [Silymarin was dissolved in 0.2 ml of propylene glycol in saline 75/25 v/v]. The second group were injected with CDDP (7.5 mg /kg, I.P.), whereas animals in the third group were i.p. injected with silymarin at a dose of 100 mg/kg/day for 5 consecutive days. The Fourth group received a daily i.p. injection of silymarin (100 mg/kg/day for 5 days) 1 hr before a single i.p. injection of CDDP (7.5 mg/kg). CDDP hepatotoxicity was manifested biochemically by an increase in serum ALT and AST, elevation of MDA and NO in liver tissues as well as a decrease in GSH and the activities of antioxidant enzymes, including SOD, GSHPx in liver tissues. In addition, marked decrease in serum NO, albumin and calcium levels were observed. Serum ALT, AST, liver NO level, MDA was found to decreased in the combination group in comparison with the CDDP group. The activities of SOD, GSHPx, GSH and serum NO were lower in CDDP group than both the control and CDDP pretreated with silymarin groups. The results obtained suggested that silymarin significantly attenuated the hepatotoxicity as an indirect target of CDDP in an animal model of CDDP-induced nephrotoxicity.     

The chemopreventive effect of Ginkgo biloba and Silybum marianum extracts on hepatocarcinogenesis in rats

Background/objective

This study was designed to evaluate the potential chemopreventive activities of Ginkgo biloba extract (EGb) and Silybum marianum extract (silymarin) against hepatocarcinogenesis induced by N-nitrosodiethylamine (NDEA) in rats.

Methods

Rats were divided into 6 groups. Group 1 served as normal control rats. Group 2 animals were intragastrically administrated NDEA at a dose of 10 mg/kg five times a week for 12 weeks to induce hepatocellular carcinoma (HCC). Groups 3 and 4 animals were pretreated with silymarin and EGb respectively. Groups 5 and 6 animals were posttreated with silymarin and EGb respectively. The investigated parameters in serum are alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT) and vascular endothelial growth factor (VEGF). The investigated parameters in liver tissue are malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and comet assay parameters.

Results

In NDEA group, MDA level was elevated with subsequent decrease in GSH level and SOD, GPx and GR activities. In addition, NDEA group revealed a significant increase in serum ALT, AST and GGT activities and VEGF level. Furthermore, NDEA administrated animals showed a marked increase in comet assay parameters. These biochemical alterations induced by NDEA were confirmed by the histopathological examination of rat livers intoxicated with NDEA that showed an obvious cellular damage and well differentiated HCC. In contrast, silymarin+NDEA treated groups (3&;5) and EGb+NDEA treated groups (4&;6) showed a significant decrease in MDA level and a significant increase in GSH content and SOD, GPx and GR activities compared to NDEA group. Silymarin and EGb also beneficially down-regulated the increase in serum ALT, AST, GGT activities and VEGF level induced by NDEA. In addition, silymarin and EGb significantly decreased comet assay parameters. Histopathological examination of rat livers treated with either silymarin or EGb exhibited an improvement in the liver architecture compared to NDEA group.

Conclusions

The obtained findings suggested that silymarin and EGb may have beneficial chemopreventive roles against hepatocarcinogenesis through their antioxidant, antiangiogenic and antigenotoxic activities.     

Impacts of exposure to 900 MHz mobile phone radiation on liver function in rats

Objective: To study the impacts of exposure to electromagnetic radiation(EMR) on liver function in rats. Methods: Twenty adult male Sprague-Dawley rats were randomly divided into normal group and radiated group. The rats in normal group were not radiated, those in radiated group were exposed to EMR 4 h/d for 18 consecutive days. Rats were sacrificed immediately after the end of the experiment. The serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST), and those of malondialdehyde(MDA) and glutathione(GSH) in liver tissue were evaluated by colorimetric method. The liver histopathological changes were observed by hematoxylin and eosin staining and the protein expression of bax and bcl-2 in liver tissue were detected by immunohistochemical method. Terminal-deoxynucleotidyl transferase mediated nick and labelling(TUNEL) method was used for analysis of apoptosis in liver. Results: Compared with the normal rats, the serum levels of ALT and AST in the radiated group had no obvious changes(P0.05), while the contents of MDA increased(P0.01) and those of GSH decreased(P0.01) in liver tissues. The histopathology examination showed diffuse hepatocyte swelling and vacuolation, small pieces and focal necrosis. The immunohistochemical results displayed that the expression of the bax protein was higher and that of bcl-2 protein was lower in radiated group. The hepatocyte apoptosis rates in radiated group was higher than that in normal group(all P0.01). Conclusion: The exposure to 900 MHz mobile phone 4 h/d for 18 days could induce the liver histological changes, which may be partly due to the apoptosis and oxidative stress induced in liver tissue by electromagnetic radiation.     

不同剂量乳化异氟醚预处理对大鼠肝脏缺血再灌注损伤的保护作用

摘要 目的：探究不同剂量乳化异氟醚预处理对大鼠肝脏缺血再灌注损伤的保护作用。方法：将48只成年雄性大鼠随机分为六组：假手术组、缺血对照组、脂肪乳组、低剂量乳化异氟醚组、中剂量乳化异氟醚组和高剂量乳化异氟醚组,每组8只。检测血清中酶的含量,观察肝细胞损伤程度,直观的反应乳化异氟醚预处理对肝脏缺血再灌注损伤的影响。结果：不同组别大鼠肝脏再灌注后ALT、AST、LDH和MDA含量,SOD活性和肝细胞坏死比例均具有显著差异,随着再灌注时间的延长,各组大鼠血清ALT、AST和LDH含量均明显增加（均P＜0.05）。再灌注后1 h、2 h和4 h中剂量乳化异氟醚组大鼠血清ALT、AST和LDH含量均显著低于缺血对照组、低剂量乳化异氟醚组和高剂量乳化异氟醚组（均P＜0.05）。中剂量乳化异氟醚组大鼠肝组织匀浆中MDA含量和肝细胞坏死比例均显著低于缺血对照组、低剂量乳化异氟醚组和高剂量乳化异氟醚组,SOD活性显著高于缺血对照组、低剂量乳化异氟醚组和高剂量乳化异氟醚组（均P＜0.05）。结论：中等剂量乳化异氟醚预处理组中血清中酶含量最低,肝组织匀浆中MDA含量最低,SOD活性水平最高,肝细胞损伤程度最轻,对大鼠肝脏缺血再灌注的保护作用最好。     

银杏叶提取物对对乙酰氨基酚诱导的小鼠急性肝损伤的保护作用

目的：探究银杏叶提取物（GBE）对对乙酰氨基酚（APAP）诱导的小鼠急性肝损伤的保护作用及其机制。方法：30只小鼠随机分为对照组、模型组、GBE低、中、高剂量组（50,100,and 200 mg·kg^-1）,每组6只。除对照组外,剩余小鼠腹腔注射APAP （300 mg/kg）一次,随后GBE低、中、高剂量组按照相应剂量灌胃给药,治疗2 d后取材。观察各组肝脏大体情况和肝组织的病理组织学变化;取血测定各组小鼠血清中ALT、AST的活性和TNF-α、IL-6的水平;取肝检测各组肝组织中SOD、MPO的活性和GSH、MDA的含量;通过Western blot检测各组肝组织中Nrf2、HO-1蛋白的表达量。结果：与对照组相比,模型组肝脏明显肿大,病理表现差,血清中ALT、AST、TNF-α、IL-6的水平显著升高（P<0.01）,肝组织中GSH的含量和SOD的活性显著降低（P<0.01）,MDA的含量和MPO的活性显著升高（P<0.01）,Nrf2、HO-1蛋白表达明显下调（P<0.01）。与模型组相比,GBE组肝脏肿大减轻,病理表现有所改善,血清中ALT、AST、TNF-α、IL-6的水平显著降低（P<0.01）,肝组织中GSH的含量和SOD的活性显著提高（P<0.01）,MDA的含量和MPO的活性显著降低（P<0.01）,Nrf2、HO-1蛋白表达上调（P<0.05）,其中高剂量GBE组治疗效果最明显。结论：GBE可对APAP诱导的小鼠急性肝损伤具有保护作用,其作用机制可能是通过Nrf2/HO-1抗氧化途径发挥作用。