邻苯二甲酸二(2-乙基己基)酯、氯氰菊酯单独及联合染毒对青春前期雄性大鼠生殖发育的不良影响

目的探讨邻苯二甲酸二(2-乙基己基)酯(DEHP)和氯氰菊酯(CYP)单独及联合染毒对青春前期雄性大鼠生殖发育的不良影响。方法选择SPF级3周龄雄性SD大鼠24只,随机分为4组,分别为对照组(喂饲玉米油)、DEHP染毒组(500mg/kg)、CYP染毒组(80mg/kg);DEHP、CYP联合染毒组(DEHP 500mg/kg+CYP 80mg/kg),每组6只。采用经口灌胃方式染毒,每天1次,连续染毒30天。于末次染毒24小时后处死动物,测定大鼠体重、睾丸湿重,并计算睾丸系数;测定血清睾酮水平;制备睾丸病理组织切片,光镜观察其组织学改变,电镜观察生殖细胞超微结构;测定睾丸标志酶乳酸脱氢酶(LDH)、酸性磷酸酶(ACP)、碱性磷酸酶(ALP)和琥珀酸脱氢酶(SDH)的活性。结果与对照组相比,DEHP、CYP单独及联合染毒组睾丸下降时间和包皮分离时间明显延迟,肛门生殖器间距明显缩短(P<0.05或0.01);DEHP单独染毒组睾丸重量及睾丸系数明显降低,血清睾酮水平显著下降(P<0.05),睾丸匀浆中ALP、ACP和LDH活性明显增高,SDH活性显著下降(P<0.01);DEHP、CYP单独及联合染毒组睾丸病理组织学、生殖细胞超微结构均可见明显异常。结论 DEHP、CYP单独及联合染毒对青春前期雄性大鼠均具有明显的生殖毒性作用,可引起生精细胞、支持细胞和间质细胞的变性、坏死及功能障碍,从而导致雄性生殖系统发育和功能的显著异常。其中,DEHP单独染毒呈现主效应,DEHP、CYP联合染毒对大鼠的生殖毒性未呈现明显交互影响。     

巴豆醛致雄性大鼠神经毒性作用的研究

目的探讨巴豆醛暴露致雄性大鼠神经毒性作用,分析其可能的作用机制。方法于2019年7至10月,将24只SPF级雄性Wistar大鼠随机分为对照组和2.5、4.5、8.5 mg/kg染毒组,每组6只,分别经口给予0.0、2.5、4.5、8.5 mg/kg体重巴豆醛溶液,每周5次,连续染毒90 d。染毒结束后,测量大鼠体重,麻醉解剖取大鼠大脑组织和肝组织。测定大脑组织乙酰胆碱酯酶(AChE)活力及肝组织乙酰胆碱(ACh)水平;检测大脑组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力以及丙二醛(MDA)和还原型谷胱甘肽(GSH)水平;酶联免疫吸附测定(ELISA)法检测大脑组织中白细胞介素6(IL-6)、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)水平。结果与对照组比较,2.5、4.5、8.5 mg/kg染毒组大鼠大脑组织中AChE活力明显降低,8.5 mg/kg染毒组大鼠肝组织中ACh水平明显升高,差异均有统计学意义(P<0.05);与对照组比较,4.5、8.5 mg/kg染毒组大鼠大脑组织中MDA水平明显升高,GSH水平和SOD、GSH-Px活力明显降低,差异均有统计学意义(P<0.05);与对照组比较,2.5、4.5、8.5 mg/kg染毒组大鼠大脑组织中TNF-α、IL-6水平明显升高,4.5、8.5 mg/kg染毒组IL-1β水平明显升高,差异均有统计学意义(P<0.05)。结论巴豆醛暴露可致大鼠神经系统损伤,可能与氧化平衡状态改变及上调大脑组织炎性因子表达等作用有关。     

锰对大鼠脑谷氨酸代谢及酶活性影响

目的 研究不同剂量锰对大鼠纹状体谷氨酰胺合成酶(GS)、谷氨酰胺酶(PAG)和脑皮质琥珀酸脱氢酶(SDH)、钠钾三磷酸腺苷酶(Na -K -ATPase)活性的影响,以探讨锰的兴奋性毒性的细胞分子学机制.方法 大鼠按体重随机分成4组,每组6只.第1组为对照组,腹腔注射0.9%的氯化钠,第2～4组为锰染毒组,分别腹腔注射8,40,200 μmol/kg的氯化锰溶液,注射容量为5 ml/kg.染毒25 d后,测定纹状体GS和PAG的活性和脑皮质SDH和Na -K -ATPase的活性.结果 随着染锰剂量的增加,脑皮质SDH和Na -K -ATPase活性降低,200μmol/kg染锰组与对照组比较,SDH和Na -K -ATPabe活性明显降低(P＜0.01);随着染锰剂量的增加,GS活性降低,PAG活性升高,200 μmol/kg染锰组与对照组比较,GS活性明显降低(P＜0.01),PAG活性明显升高(P＜0.05).结论 锰可引起大鼠脑SDH、Na -K -ATPase和GS活性降低以及PAG活性升高,造成谷氨酸代谢失衡.     

三乙醇胺染毒对大鼠机体危害的研究

[目的]实验观察三乙醇胺染毒大鼠血清脂质过氧化代谢产物(MDA)含量,超氧化歧化酶(SOD)和全血谷胱甘肽氧化酶(GSH-PX)的活性及组织病理学改变。[方法]32只大鼠分别经染毒不同剂量的三乙醇胺(250、500、750mg/kg),每周1次,7周后断头取血检测酶学指标,同时进行大体剖检和组织病理学检查。[结果]染毒大鼠血清MDA含量明显增高,SOD和全血GSH-PX活性明显降低,与对照组比较差异均有统计学意义(P＜0.01);500mg/kg、750mg/kg染毒组脏器系数增大,肝、脾、肾器官有不同程度的病理学改变。[结论]接触一定量的三乙醇胺可增强染毒大鼠脂质过氧化水平,对染毒大鼠肝、脾、肾脏组织有损伤作用。     

乙醇联合二甲基甲酰胺致小鼠急性肝损伤的作用研究

目的研究乙醇联合二甲基甲酰胺(N,N-dimethylformamide,DMF)致小鼠急性肝损伤的作用。方法选用C57BL/6小鼠64只,随机分为8组,每组8只。其中3组为DMF模型1、2、3组,3组为乙醇+DMF 1、2、3组,另2组分别为正常对照组和20%乙醇对照组。采用DMF致小鼠急性肝损伤模型,染毒48 h后,测定血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和乳酸脱氢酶(LDH)的活力;留取肝脏组织,常规石蜡包埋切片,HE染色,用光学影显微镜观察肝脏组织病理变化;制备肝匀浆,测定肝组织中还原型谷胱甘肽(GSH)、氧化型谷胱甘肽(GSSG)、丙二醛(MDA)的含量。结果与阴性对照组相比,DMF模型组小鼠血清中ALT、AST和LDH活力随着剂量的增加而不断的升高,肝脏组织出现明显的肝细胞变性坏死;乙醇联合DMF可以明显升高小鼠血清中ALT、AST和LDH的活力,增加肝组织中MDA的含量,降低GSH和GSH/GSSG的比值,肝组织病理损伤明显加重;乙醇对照组上述指标均无明显变化。结论乙醇可加重DMF致小鼠急性肝损伤的作用。     

三唑磷杀虫剂的亚慢性毒性研究

[目的]研究三唑磷杀虫剂对大鼠的亚慢性毒性作用。[方法]设4组，每组13只雌性和13只雄性别大鼠连续13周分别以含三唑磷0、1、20、400mg/kg摄食染毒，观察大鼠一般状况、体重及饲料、水消耗状况，并于第7和13周分别取大鼠的尿分析尿常规指标，于第13周取大鼠的血分析血常规和生化指标；于染毒后第2、4、6、13周分别取大鼠的血液分析其全血胆碱酯酶活性；于染毒后第13周处死全部大鼠，取其脏器称重计算脏器系数，并通过病理组织检查分析对脏器的损害情况。[结果]各剂量组大鼠13周内均无死亡。400mg/kg剂量组大鼠的体重明显低于对照组，肝脏脏器系数以及血碱性磷酸酶、甘油三酯指标明显高于对照组。20、400mg/kg组的红细胞数和血红蛋白数明显低于对照组。胆碱酯酶活性4周时400mg/kg剂量组雌鼠抑制率37．1％，雄鼠抑制串29．2％；20mg/kg剂量组雌鼠抑制率15．7％，雄鼠抑制率13．2％；6周时1mg/kg剂量组雌鼠抑制率12％，雄鼠抑制率6．9％。[结论]大鼠13周连续摄入400mg/kg剂量的三唑磷对体重和肝脏有轻微影响。三唑磷最低观察到毒作用剂量为20mg/kg，最大未观察到毒作用剂量为1mg/kg。     

三氯异氰尿酸对大鼠的亚慢性毒性

将SD大鼠按性别、体重随机分为高剂量组(1/8LD50)、中剂量组(1/16 LD50)、低剂量组(1/64LD50)和阴性对照组,分别喂饲相应的受试物饲料90 d,观察大鼠体重、血常规、尿常规、血清生化、脏体系数和组织病理学变化。结果与对照组相比,高剂量组雌性大鼠在染毒第70 d后生长明显减缓并持续到实验结束,AST、ALT活性明显升高;雄性大鼠睾丸脏体系数明显增大,AST、BUN显著升高。中剂量组雄性大鼠AST、BUN也明显增高。低剂量组各指标变化不明显。各剂量组脏器组织未见明显异常改变。提示三氯异氰尿酸原药对动物体重增长有抑制作用,对肝、肾功能有不良影响。经口染毒的亚慢性毒性阈剂量雌雄大鼠分别为99.25、49.62 mg/kg,最大无作用剂量雌雄大鼠分别为49.62、12.41 mg/kg。     

除草剂2-甲-4氯苯氧乙酸对雄性小鼠的毒作用

目的观察除草剂2-甲-4-氯苯氧乙酸(MCPA)对雄性小鼠的毒作用。方法将雄性昆明种小鼠随机分为4组,每组10只。对照组给予蒸馏水灌胃,其余3组分别以20、100和200mg/kgMCPA灌胃,每天1次,每周6次,连续17d。测定小鼠的体重、甲状腺素(T4)、三碘甲腺原氨酸(TSH)、胆固醇含量、脾和睾丸的脏器系数、睾丸组织中的乳酸脱氢酶(LDH)和山梨醇脱氢酶(SDH)的比活性。结果与对照组比较,各MCPA染毒组体重增长缓慢。200mg/kg组的脾系数、血清TSH明显低于对照组。血清胆固醇含量随剂量升高而上升。与对照组比较,20mg/kg组T4升高有显著性(P<0.05);200mg/kg组T4降低有显著性(P<0.05);睾丸系数随剂量的增加而明显降低,睾丸组织中的LDH活性各染毒组均明显升高,但SDH未见明显变化。结论除草剂MCPA可抑制雄性小鼠体重增长,并导致内分泌功能紊乱、脾萎缩,具有生殖毒性。     

二硝酰胺铵的亚急性经皮毒性

选用SPF级SD大鼠40只，雌雄各半，按体重随机分为对照组和二硝酰胺铵（ADN）250、500、1 000 mg/kg染毒组，连续经皮染毒4周，7 d/周，于末次染毒24 h后处死，观察各组大鼠的一般状况、血液和血生化指标、脏器系数及病理组织学变化。结果显示，各组大鼠无死亡且未出现明显异常症状，体重变化差异无统计学意义（P>0.05）。血液学检测各染毒组大鼠血常规RBC、WBC、Plt与对照组相比差异均无统计学意义（P>0.05）。血清生化指标检测与对照组相比，1 000 mg/kg染毒组雌性大鼠总胆红素（TBiL）、天冬氨酸氨基转移酶（AST）升高（P<0.05），谷氨酰转移酶（GGT）降低（P<0.05）；1 000 mg/kg染毒组雄性大鼠总蛋白（TP）、白蛋白（ALB）、球蛋白（GLB）、乳酸脱氢酶（LDH）及AST升高（P<0.05），GGT降低（P<0.05）。与对照组相比，1000 m/kg染毒组大鼠肝/体比值明显降低（P<0.05）。病理组织学观查示1 000 mg/kg染毒组肝组织结构轻度紊乱，肝细胞水肿、坏死。提示ADN对大鼠的亚急性经皮染毒无可见有害作用水平（NOAEL）为500 mg/kg，毒作用靶器官主要为肝脏。     

β-烟酰胺单核苷酸的急性及亚急性经口毒性

β-烟酰胺单核苷酸(NMN)急性经口毒性试验采用最大限量法,将大、小鼠分别设置对照组和5000mg/kg剂量组,每组10只动物,雌雄各半,进行一次性经口灌胃染毒。28d重复剂量亚急性经口毒性试验,将大鼠分为对照组和1000mg/kg剂量组,每组10只大鼠,雌雄各半,连续灌胃染毒28d,记录动物摄食和体质量变化,染毒后检测动物血常规和血清生化指标。取大鼠主要脏器,计算脏器系数并制作病理组织切片。结果显示,急性经口毒性试验未见动物明显异常。亚急性经口毒性试验1000mg/kg剂量染毒组大鼠体质量、摄食量、食物利用率、血常规及生化指标与对照组相比差异均无统计学意义(P>0.05),肝、肾脏器质量和脾脏器系数与对照组相比,差异有统计学意义(P<0.05)。组织学检查未见病理性损伤。NMN急性经口毒性试验半数致死剂量(LD₅₀)>5000mg/kg,亚急性经口毒性试验最大无作用剂量(NOAEL)>1000mg/kg。     

马齿苋的抗低氧作用及其机制研究

目的观察不同浓度马齿苋水提液对低氧小鼠的保护作用及其机制.方法以生理盐水和人参总皂苷为对照,观察不同浓度马齿苋水提液对密闭低氧条件下小鼠存活时间的影响,采用生物化学方法测定丙酮酸激酶（PK）和磷酸果糖激酶（PEK）活性,荧光素酶法测定ATP含量,定磷法测定Na＋,K＋-ATP酶活性,分光光度法测定乳酸含量,2,4二硝基苯肼比色法测定乳酸脱氢酶（LDH）活性.结果 （1）0.5,1.0,2.0g/ml 3种浓度的马齿苋水提液分别延长密闭低氧小鼠的生存时间24%,36.5%和27.4%;（2）1g/ml马齿苋水提液可明显增强低氧小鼠心、脑细胞PK、PEK活性,缓解细胞内ATP含量下降幅度,提高Na＋,K＋-ATP、Ca2＋,Mg2＋-ATP和LDH等酶的活性.结论马齿苋水提液可提高小鼠耐低氧能力,机制之一可能是其促进低氧小鼠无氧酵解关键酶的活性,进而缓解因低氧引起能量代谢障碍所致的细胞损伤.     

N—乙酰半胱氨酸对二甲基甲酰胺所致急性肝损伤的保护作用

目的 探讨N-乙酰半胱氨酸(NAC)对二甲基甲酰胺(DMF)所致急性肝损害的保护作用。方法 给小鼠腹腔注射一次1800mg/kg DMF后用NAC灌胃。测定血清山梨醇脱氢酶(SDH)、丙氨酰氨基转移酶(ALT)、甘胆酸(CG)、肝脏谷胱甘肽(GSH)、Na~ K~ -ATP酶、Ca~(2 )-ATP酶,观察肝脏病理改变。结果 与单纯染毒组比较,染毒后连续口服NAC组血清SDH、ALT、CG明显降低(P<0.05),肝脏GSH含量升高,Na~ K~ -ATP酶、Ca~(2 )-ATP酶活性增高(P<0.05),肝脏病理改变减轻。结论 NAC对DMF所致急性肝损伤有一定保护作用。     

Effect of 2,4-dichlorophenoxyacetic acid on the activities of some metabolic enzymes for generating pyridine nucleotide pool of cells from mouse liver

2,4-Dichlorophenoxyacetic acid (2,4-D), which is a plant auxin analogue, is lethal to broad leaved weeds within days at high dosages and is considered as having low toxicity to mammals. Some studies have reported that exposure to this compound may cause damage to organs such as liver. The aim of this study was to investigate the effects of 2,4-D in mouse liver on chromosomes as well as hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) which are required for the generation of the pyridine nucleotide pool. The experiments were carried out with a 2,4-D group, an ethanol control for 2,4-D, and saline group for ethanol control group on three generations of mice. Only female parents were given 2,4-D during the gestation period, lactation period and for 33 days following the lactation period. In females of the first cross, 2,4-D caused a significant increase in the activity of LDH, and ethanol alone caused a significant increase in the activities of HK and LDH. In the male offspring of the first cross maternal, 2,4-D caused a significant increase in the activity of LDH, and ethanol alone caused a significant decrease in the activity of 6PGD. In the female offspring of the first cross maternal, ethanol caused a significant increase in the activities of G6PD and MDH. In the female offsprings of the third cross maternal, 2,4-D caused a significant increase in the activity of MDH. No gross morphological changes were observed in internal organs, such as liver, kidney and spleen of the affected animals. Also, a chromosomal study from bone marrow cells indicated no anomalies in chromosomal sets and structures. As a result, 2,4-D had an effect on the first cross maternal and their offsprings. The compound did not affect the parameters studied except MDH enzyme activity in the second and third generation of mice.     

Relative hepatotoxicity of some industrial solvents after intraperitoneal injection or inhalation exposure in rats

Intraperitoneal LD50 (lethal dose 50% kill) values and minimal liver toxic doses in female Sprague-Dawley rats were determined for the following industrial solvents: toluene, methylene chloride, carbon tetrachloride, 1,1,1-trichloroethane, 1,1,2-trichloroethane, trichloroethylene, ethanol, methyl ethyl ketone, and dioxane. For the following solvents LC50 values and minimal liver toxic air concentrations were also determined: xylene, styrene, chloroform, tetrachloroethylene, and dimethylformamide (DMF). The serum activity of the enzyme sorbitol dehydrogenase (SDH) was used as an indicator of liver damage. Carbon tetrachloride, chloroform, and DMF were hepatotoxic in low doses compared to LD50 values (TD50 (toxic dose 50%) values approximately 30, 90, and 50 mg/kg). Chloroform and DMF were hepatotoxic in comparatively low concentrations after a 4-hr inhalation exposure (TC50 (toxic concentration 50%) values approximately 590 and 740 mg/m3). Even relatively high doses of the other solvents did not raise the SDH activity. Significant direct (metabolite-mediated) hepatotoxicity seems to be an uncommon feature among commonly used industrial solvents.     

ZnCl2对二甲基甲酰胺所致小鼠急性肝毒性的保护作用研究

目的 研究ZnCl2对二甲基甲酰胺(N,N-dimethylformamide,DMF)致小鼠急性肝损伤的保护作用,为保护DMF接触人群提供指导.方法 将80只动物随机分为8组:正常对照组、DMF组、ZnCl2-10 DMF组、ZnCl2-20 DMF组、ZnCl2-40 DMF组、ZnCl2-10组、ZnCl2-20组和ZnCl2-40组.所有ZnCl2给药组每天皮下注射一定剂量的ZnCl2溶液.ZnCl2-10、ZnCl2-20和ZnCl2-40组在DMF染毒之前,其余组在DMF染毒后48 h处死小鼠,测定其血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)和乳酸脱氢酶(LDH)的活力;制备肝匀浆,测定ZnCl2-10、ZnCl2-20和ZnCl2-40组小鼠肝金属硫蛋白(MT)含量;留取肝脏组织,常规石蜡包埋切片,HE染色,光镜观察肝脏组织病理变化.结果 与正常组比较,DMF组小鼠血清中ALT、AST和LDH活力明显升高,肝脏组织出现明显的肝细胞变性坏死;ZnCl2 DMF组的小鼠血清中ALT、AST和LDH活力与DMF组相比明显降低,肝脏组织病理损伤明显减轻.单独给予ZnCl2组小鼠MT含量升高.结论 ZnCl2对DMF引起的小鼠急性肝损伤具有明显的保护作用.     

硒拮抗氟诱导肾脂质过氧化及酶组织化学改变的研究

给ＳＤ大鼠饮用含氟化钠，亚硒酸钠，氟化钠和亚硒酸钠的水溶液８周，观察硒对氟诱导肾脏脂质过氧化及肾酶组织化学改变的影响。结果表明，氟可使肾脏脂质过氧化物含量明显增加，并可使肾近曲小管上皮细胞琥珀酸脱氢酶（ＳＤＨ）和碱性磷酸酶（ＡＬＰ）活性明显降低，乳酸脱氢酶（ＬＤＨ）和酸性磷酸酶（ＡＣＰ）活性明显增高。同时补硒可促进肾脏的氟排泄，降低肾脏脂质过氧化物含量，对氟引起的生物膜损伤具有较强的防护作用，从而减轻氟对肾近曲小管上皮细胞中ＳＤＨ、ＡＣＰ活性的影响，而硒对氟所致的肾近曲小管上皮细胞ＡＬＰ、ＬＤＨ活性改变的拮抗作用则不明显。可以认为，硒对氟致肾损害具有一定拮抗作用。     

延胡索酸二甲酯对大鼠醌还原酶和谷胱甘肽—S—转移酶的诱导作用

目的　探讨延胡索酸二甲酯（ＤＭＦ） 对大鼠主要脏器醌还原酶和谷胱甘肽Ｓ转移酶的诱导作用和意义。方法　雄性Ｗｉｓｔａｒ 大鼠饮食中补充０ ．２ ％ ＤＭＦ,于６ 、２４ 、７２ 小时、１ 和２ 周后取血并处死动物,用酶动力学法测定大鼠腺胃、肝、肺、肾和心脏中的醌还原酶（ＱＲ） 和谷胱甘肽Ｓ转移酶（ＧＳＴｓ） 活性,并按此法测定血清ＱＲ、ＧＰＴ和乳酸脱氢酶含量。结果　服用ＤＭＦ２４ 、７２ 小时、１ 和２ 周后可观察到腺胃、肝、肺、肾脏中ＱＲ 和ＧＳＴｓ 活性显著增高（ Ｐ＜ ０ ．０００ １ 或Ｐ＜ ０ ．０１） ,同时血清ＱＲ 活性也显著增高（ Ｐ＜ ０ ．０１ ,或Ｐ＜ ０ ．０００ １） 。ＤＭＦ对血清ＧＰＴ 和乳酸脱氢酶的活性则无影响。结论　ＤＭＦ对大鼠腺胃、肝、肺、肾和血清中的ＱＲ 和ＧＳＴｓ 活性具有诱导作用,ＤＭＦ有望成为人类抗氧化损伤的保护剂和解毒剂。     

Interrelationships in rats among dietary vitamin B6, glycine and hydroxyproline. Effects of oxalate, glyoxylate, glycolate, and glycine on liver enzymes.

Urinary endogenous oxalate was increased by feeding vitamin B6-deficient or control rats with 5.2% hydroxyproline, or 3% glycine plus 5.2% hydroxyproline. The activities of liver lactic dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G6PD) , malic enzyme (ME), and ATP citrate lyase were decreased in vitamin B6-DEFICIENT RATS, AND THEIR LIVEr G6PD was further decreased by the addition of glycine and hydroxyproline to their diets. Supplementing control diets with the two amino acids decreased the activities of rat liver LDH, G6PD, and ATP citrate lyase. The effects of glycine and hydroxyproline feeding on the enzymes studied did not appear related to alterations in insulin availability. Since in vitamin B6-deficient rats, there are increases in urinary levels of oxalic and glycolic acids, and glycine, and increases in tissue levels of glyoxylic acid and glycine, the effects of these metabolites on the activities of the above mentioned enzymes were measured. Oxalic acid inhibited the activities of LDH, G6PD, and ME. Glyoxylic acid inhibited LDH and ME, but not G6PD. Glycolic acid inhibited G6PD and ME, but not LDH. ATP citrate lyase was not affected by these substances. Glycine had no effect on the enzymes studied. Diets which increased oxalate excretion generally reduced or did not alter liver and kidney levels of oxalate, glycolate, and glyoxylate. However, the feeding of glycine and hydroxyproline increased kidney oxalate, and liver and kidney glyoxylate in vitamin B6-deficient rats.     

Chronic ethanol and nicotine interaction on rat tissue antioxidant defense system.

Ethanol consumption and cigarette smoking are common in societies worldwide and have been identified as injurious to human health. This study was undertaken to examine the interactive effects of chronic ethanol and nicotine consumption on the antioxidant defense system in different tissues of rat. Male Fisher-344 rats were divided into four groups of five animals each and treated for 6.5 weeks as follows: (1) Control rats were administered normal saline orally; (2) ethanol (20% [wt./vol.]) was given orally at a dose of 2 g/kg; (3) nicotine was administered subcutaneously at a dose of 0.1 mg/kg; and (4) a combination of ethanol plus nicotine was administered by the route and at the dose described above. The animals were killed 20 h after the last treatment, and liver, lung, kidney, and testes were isolated and analyzed. Chronic ingestion of ethanol resulted in a significant depletion of glutathione (GSH) content in liver, lung, and testes, whereas chronic administration of nicotine significantly depleted GSH content in liver and testes. The combination of ethanol plus nicotine resulted in a significant depletion of GSH content in liver, lung, and testes. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly increased superoxide dismutase (SOD) activity in liver and decreased SOD activity in kidney. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly decreased catalase (CAT) activity in liver and increased CAT activity in kidney and testes. Chronic ingestion of ethanol resulted in a significant decrease in glutathione peroxidase (GSH-Px) activity in liver and kidney, whereas a combination of ethanol plus nicotine increased GSH-Px activity in liver and decreased GSH-Px activity in kidney and testes. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly increased lipid peroxidation, respectively, in liver. It is suggested that prolonged exposure to ethanol and nicotine produce similar, and in some cases additive, oxidative tissue injuries in rat.     

沙棘油对汞致急性肝、肾损伤的保护作用

[目的]探讨急性染汞致大鼠肝、肾毒性的作用机制,观察沙棘油（SBO）的保护作用。[方法]24只Wistar大鼠随机均分为：阴性对照组（皮下注射0．9％生理盐水）;染汞组（皮下注射2．5mg／kgHgCl：）;SBO＋HgCl2组[灌胃SBO（体积分数为95％）5mL／kg,2h后皮下注射2．5mg／kgHgCl2］。染汞后12h将大鼠移入代谢笼,收集12h尿样。染汞48h后处死,采取血样和肝肾组织。测定肝脏、肾皮质和尿汞含量;尿N-乙酰-β—D-氨基葡萄苷酶（NAG）、碱性磷酸酶（ALP）、乳酸脱氢酶（LDH）活性和尿蛋白、血清尿素氮（BUN）含量;肝、肾中谷胱甘肽（GSH）、丙二醛（MDA）、蛋白含量和超氧化物岐化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性。[结果]与对照组相比,HgCl2组、SBO＋HgCl2组的肝、肾皮质及尿汞含量均明显增加（P〈0．01）;与HgCl2组相比,SBO＋HgC｜2组尿汞含量增加（P〈0．05）。HgCl2组尿NAG、ALP、LDH活性和尿蛋白、BUN含量均明显高于对照组（P〈0．01）;SBO＋HgCl2组NAG、ALP活性和BUN含量均低于HgCl2组（分别为P〈0．05,P〈0．01和P〈0．01）。与对照组相比,HgCl2组肝、肾GSH含量、GSH—Px活性、SOD活性均下降（P〈0．01）,MDA含量增加（P〈0．05或P〈0．01）;SBO＋HgCl2组与HgCl2组相比,其肝GSH-Px活性明显增加（P〈0．01）。[结论]大鼠经一次染汞后可致急性肝、肾损伤。沙棘油具有促进汞从肾脏排出的作用,对汞致肝脏氧化损伤有一定保护作用。