8-甲氧补骨脂素对对乙酰氨基酚致小鼠急性肝损伤的保护作用

目的研究8-甲氧补骨脂素(8-methoxypsoralen,8-MOP)对对乙酰氨基酚(acetaminophen,APAP)致小鼠急性肝损伤的保护作用。方法采用对乙酰氨基酚所致小鼠急性肝损伤模型。24 h后,检测小鼠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);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;制备肝匀浆,测定肝中还原型谷胱甘肽(GSH)、氧化型谷胱甘肽(GSSG)和丙二醛(MDA)的含量。结果与正常对照组比较,模型组小鼠血清中ALT、AST和LDH活性明显升高,肝脏组织出现明显的肝细胞变性坏死;与模型组相比,8-甲氧补骨脂素可以明显降低小鼠血清中ALT、AST和LDH的活性,降低肝组织中MDA的含量,升高GSH/GSSG比值,肝组织病理损伤也明显减轻。结论 8-甲氧补骨脂素对对乙酰氨基酚致小鼠急性肝损伤具有明显的保护作用。     

The effect of sub-acute and sub-chronic exposure of rats to the glyphosate-based herbicide Roundup

Roundup is a glyphosate-based herbicide that includes 78.5% glyphosate and surfactant at lower toxic concentrations. Glyphosate is an organophosphorated non-selective agrochemical widely used in many countries including Turkey and acts after the sprout in a systemic way. The objective of this study was to analyze toxic effects of the herbicide Roundup in rat liver. Animals were treated with 56mg/kg (p.o.) and 560mg/kg (p.o.) of Roundup (78% glyphosate+surfactant) each day, during 5 and 13 weeks. Hepatotoxicity was monitored by quantitative analysis of the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities and measured amount of serum lipoprotein (LDL, HDL), total cholesterol and creatinine were used as the biochemical markers of liver damages. Besides the biochemical analysis, we also investigated liver tissues histopathologically. Sub-chronic treatment, starting from the low and high doses of Roundup, it was observed that there were mild effects on activity of ALT, AST and LDH enzymes indicating the hepatic toxicity induced by Roundup. It was found that the mild effects were different on the enzymes in male and female rats of treatment groups. Also it was found some difference in serum lipoprotein (LDL, HDL) and t-cholesterol. There was no difference creatinine value between control and treatment groups but it was observed that degenerative formation such as mononuclear cell infiltration and congestion of the liver tissues of treatment groups.     

5'-核苷酸酶在肝脏疾病诊断中的应用

目的探讨血清5'-核苷酸酶(5'-NT)在肝脏疾病诊断中的应用.方法应用全自动生化仪检测对照组64例健康者,胆结石和胆囊炎组40例及肝转移癌和肝硬组40例患者血清中5'-NT、ALT、AST、GGT、AFU、PA等相关肝功能生化指标,并对结果进行统计学分析.结果对照组5'-NT活性正常,ALT、AST、GGT、AFU、PA亦正常;而胆结石和胆囊炎组、肝转移癌和肝硬化组患者的5'-NT活性水平明显升高.异常率分别为90.5%,92.7%(P＜0.05).同时,5'-NT的变化与ALT、AST、GGT、AFU、PA的变化相平行,以不同方面反映肝脏疾病患者的肝脏病变率.结论 5'-NT是诊断肝脏疾病的一项较为敏感的生化指标,结合肝功能其它项目的检测,有助于提高肝脏疾病诊断的敏感度和特异性.     

Biochemical study on the effects of some Egyptian herbs in alloxan-induced diabetic rats

The present study was carried out to investigate the effects of Lupinus albus, L. (Lupinus termis), family L. leguminosae, Cymbopogon proximus, (Halfa barr), family Gramineae, and Zygophyllum coccineum L. (Kammun quaramany), family L. Zygophyllacae on biochemical parameters in alloxan-induced diabetic rats. A dose of 1.5 ml of aqueous suspension of each herb/100 g body weight (equivalent to 75 mg/100 g b.wt.) was orally administered daily to alloxan-diabetic rats for 4 weeks. The levels of glucose, urea, creatinine and bilirubin were significantly (P<0.05) increased in plasma of alloxan-diabetic rats compared with the control group. In contrast, total protein and albumin were significantly decreased by 25 and 46%, respectively, versus control. Treatment of the diabetic rats with repeated doses of any one of the three herb suspensions could restore the changes of the above parameters to their normal levels after 4 weeks of treatment. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (AlP) activities were significantly (P<0.05) increased in the plasma of alloxan-diabetic rats. However, acetylcholinesterase activity was significantly (P<0.05) decreased in the plasma compared with the control group, whereas, such activity did not change in brain. The activities of AST, ALT and LDH were significantly (P<0.05) decreased in the liver of alloxan-diabetic rats by 58, 21 and 40%, respectively, and such activities increased in testes by 39, 26 and 26%, respectively, compared with the control group. Also, brain LDH was significantly (P<0.05) increased. Treatment of the diabetic rats with the aqueous suspension of the tested herbs restored the activities of the above enzymes to their normal level in plasma, liver and testes. The present results showed that the herb suspensions exerted antihyperglycemic effects and consequently may alleviate liver and renal damage caused by alloxan-induced diabetes.     

5’-核苷酸酶在肝脏疾病诊断中的应用

目的探讨血清5’-核苷酸酶(5-’NT)在肝脏疾病诊断中的应用。方法应用全自动生化仪检测对照组64例健康者,胆结石和胆囊炎组40例及肝转移癌和肝硬组40例患者血清中5’-NT、ALT、A ST、GGT、AFU、PA等相关肝功能生化指标,并对结果进行统计学分析。结果对照组5’-NT活性正常,ALT、A ST、GGT、AFU、PA亦正常;而胆结石和胆囊炎组、肝转移癌和肝硬化组患者的5’-NT活性水平明显升高。异常率分别为90.5%,92.7%(P<0.05)。同时,5’-NT的变化与ALT、A ST、GGT、AFU、PA的变化相平行,以不同方面反映肝脏疾病患者的肝脏病变率。结论5’-NT是诊断肝脏疾病的一项较为敏感的生化指标,结合肝功能其它项目的检测,有助于提高肝脏疾病诊断的敏感度和特异性。     

Combined effects of vitamin C, vitamin E, and sodium selenate supplementation on absolute ethanol-induced injury in various organs of rats

In this study, the effect of combination of vitamin C (ascorbic acid), vitamin E (alpha -tocopherol), and selenium (sodium selenate) on ethanol-induced liver and intestine injury in rats was investigated. The ethanol-induced injury was produced by the administration of 1 ml of absolute ethanol to each rats. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and sodium selenate (Se) (0.5 mg/kg) for 3 days; 1 h after the final antioxidant administration, they were sacrificed. Lipid peroxidation and glutathione levels, catalase (CAT), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase (GP(x)) activities were determined in liver and intestine tissues. Myeloperoxidase (MPO), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) were determined in liver tissue. Also, CAT activity, urea, creatinine, uric acid, and total lipid levels were determined in serum samples. In the ethanol group, serum urea, creatinine, uric acid, and total lipid levels; liver and intestine LDH; liver MPO, AST, ALP, ALT, and GGT activities; and liver and intestine LPO levels increased, whereas serum CAT activity, liver and intestine GSH levels, and CAT, SOD, and GP(x) activities decreased. On the other hand, treatment with vitamin C, vitamin E, and Se reversed these effects. As a result of these findings, we can say that the combination of vitamin C, vitamin E, and selenium has a protective effect on ethanol-induced changes in lipid peroxidation, glutathione levels, and antioxidant enzyme activities in liver and intestine tissues, and in some serum parameters of rats.     

Ginkgo biloba extract protects against mercury(II)-induced oxidative tissue damage in rats.

Mercury(II) is a highly toxic metal which induces oxidative stress in the body. In this study we aimed to investigate the possible protective effect of Ginkgo biloba (EGb), an antioxidant agent, against experimental mercury toxicity in rat model. Following a single dose of 5mg/kg mercuric chloride (HgCl(2); Hg group) either saline or EGb (150mg/kg) was administered for 5days. After decapitation of the rats trunk blood was obtained and the tissue samples from the brain, lung, liver, and kidney were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Formation of reactive oxygen species in the tissue samples was monitored by chemiluminescence (CL) technique. BUN, creatinin, ALT, and AST levels and tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) activity were assayed in serum samples. The results revealed that HgCl(2) induced oxidative damage caused significant decrease in GSH level, significant increase in MDA level, MPO activity and collagen content of the tissues. Treatment of rats with EGb significantly increased the GSH level and decreased the MDA level, MPO activity, and collagen contents. Similarly, serum ALT, AST and BUN levels, as well as LDH and TNF-alpha, were elevated in the Hg group as compared to control group. On the other hand, EGb treatment reversed all these biochemical indices. Our results implicate that mercury-induced oxidative damage in brain, lung, liver, and kidney tissues protected by G. biloba extract, with its antioxidant effects.     

The evaluation of HBDH and LDH isoenzymes in cardiac cell necrosis of the rat

The total LDH, HBDH and LDH isoenzyme activities were assessed in a number of rat tissues. HBDH did not correlate with LD1 and LD2 isoenzyme activity in tissues with high HBDH activity. HBDH therefore cannot be used as a marker for cardiac necrosis in the rat. In rats treated with isoprenaline and SK&F 94120 at doses producing myocardial necrosis, only the LD1 isoenzymes showed any significant change but only within the first 24 h of treatment. No statistically significant differences were seen in the plasma AST, CK, CK-MB and total LDH activities.     

1,3-二苯-1,3-丙二酮对可卡因致小鼠肝毒性及神经毒性的保护作用

目的:探讨1,3-二苯-1,3-丙二酮(DPPD)对可卡因致小鼠急性肝损伤及神经毒性的保护作用。方法:可卡因急性肝损伤模型采用♂C57BL/6N小鼠,DPPD(200,400,800 mg·kg–1/d,ig)预给药4 d,末次给药30 min后,sc可卡因70 mg·kg-1造模,24 h后处死,测定血清ALT,AST,LDH的活性及肝脏MDA含量,观察肝脏病理变化。DPPD抗可卡因神经毒性实验采用♂ICR小鼠,DPPD预给药3 d(给药剂量同前),末次给药30 min后,sc可卡因20mg·kg-1造模,记录小鼠0-180 min的活动次数。结果:可卡因70 mg·kg-1致部分小鼠死亡(5/7),存活小鼠血清ALT,AST,LDH活性及肝脏MDA含量显著升高,肝脏病理损伤明显,而DPPD预给药组无死亡,血清ALT,AST,LDH活性及肝脏MDA含量显著降低,肝脏损伤明显改善,呈剂量-效应关系;DPPD抗可卡因神经毒性研究发现,DPPD预给药组小鼠自主活动量较模型组显著降低。结论:DPPD对可卡因致小鼠急性肝毒性及神经毒性有拮抗作用。     

Evaluation of the toxicological effects of perfluorooctane sulfonic acid in the common carp (Cyprinus carpio)

In the present study we evaluated the toxicological effects of a scarcely documented environmental pollutant, perfluorooctane sulfonic acid (PFOS), on selected biochemical endpoints in the common carp, Cyprinus carpio. Juvenile organisms were exposed to PFOS through a single intraperitoneal injection (liver concentrations ranging from 16 to 864 ng/g after 5 days of exposure) and after 1 and 5 days effects were assessed in liver and serum of the exposed organisms. The investigation of the hepatotoxicity of PFOS included the determination of the peroxisome proliferating potential (peroxisomal palmitoyl CoA oxidase and catalase activity) and the compounds influence on the average DNA basepair length (ABPL) by agarose gel electrophoresis. Total antioxidant activity (TAA), cholesterol and triglyceride levels were monitored in the serum. After 1 day of exposure the ABPL was significantly increased in the 270 and 864 ng/g treatment groups. After 5 days of exposure significant increases relative to the control were observed for the 16, 270 and 864 ng/g treatment groups. Enzyme leakage from the liver was investigated by measurement of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in the serum. At 561, 670 and 864 ng/g PFOS a significant increase in serum ALT activity became apparent after 5 days of exposure with values ranging from 159 to 407% relative to the control. For serum AST activity a significant increase for the 864 ng/g treatment group was observed with a value of 112% relative to the control. Determination of the polymorphonuclear leukocyte migration into liver tissue as assessed through myeloperoxidase (MPO) activity in liver, was used as an indicator for inflammation. It appeared that inflammation was not involved in the observed membranous enzyme leakage for the 561, 670 and 864 ng/g PFOS treatment groups. The results of this study suggest that PFOS induces inflammation-independent enzyme leakage through liver cell membranes that might be related to cell necrosis. Furthermore, results show that PFOS does not significantly affects serum antioxidant levels nor does it clearly induce peroxisome proliferation in carp. This study also points out that PFOS might interfere with homeostasis of the DNA metabolism. The results of these biochemical analyses were used to perform an initial hazard assessment study indicating that PFOS levels observed in tissues of wildlife populations could induce a clear rise in serum transaminase levels indicative for disruption of hepatocyte membrane integrity.     

铁皮石斛无菌纳米粉抗慢性肝损伤及对肝组织超微结构的影响

目的探讨铁皮石斛无菌纳米粉(DON)的保肝作用及其相关机制。方法建立四氯化碳(CCl4)慢性肝损伤小鼠模型,同时以受试药物灌胃干预,持续8周。昆明种小鼠随机分为正常对照组、模型对照组、DON组以及铁皮石斛普通粉(DOP)组。检测各组小鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)和过氧化氢酶(CAT)活性;酶联免疫吸附测定(ELISA)检测血清中肿瘤坏死因子-α(TNF-α)和白细胞介素(IL)-6的表达;免疫组织化学法染色检测IL-1β的表达分布情况;苏木精-伊红(HE)染色行小鼠肝脏病理组织学观察;透射电镜观察肝组织超微结构变化。结果与模型对照组比较,DON和DOP干预后,血清ALT、AST、LDH水平均显著下降,CAT活性增强,TNF-α和IL-6的表达下调;免疫组化法显示,肝脏IL-1β的表达被显著抑制;肝脏病理组织学及肝细胞超微结构均有不同程度改善。与DOP组比较,DON组各项指标改善作用更显著。结论DON对慢性肝损伤具有更明显的保肝作用,其机制可能是DOP经过粒径改造后,更易促进机体抗氧化活性,抑制CCl4诱导的氧化应激,并具有抗炎作用。     

Doxorubicine-congestive heart failure-increased big endothelin-1 plasma concentration: reversal by amlodipine, losartan, and gastric pentadecapeptide BPC157 in rat and mouse

Overall, doxorubicine-congestive heart failure (CHF) (male Wistar rats and NMRI mice; 6 challenges with doxorubicine (2.5 mg/kg, i.p.) throughout 15 days and then a 4-week-rest period) is consistently deteriorating throughout next 14 days, if not reversed or ameliorated by therapy (/kg per day): a stable gastric pentadecapeptide BPC157 (GEPPPGKPADDAGLV, MW 1419, promisingly studied for inflammatory bowel disease (Pliva; PL 10, PLD-116, PL 14736)) (10 microg, 10 ng), losartan (0.7 mg), amlodipine (0.07 mg), given intragastrically (i.g.) (once daily, rats) or in drinking water (mice). Assessed were big endothelin-1 (BET-1) and plasma enzyme levels (CK, MBCK, LDH, AST, ALT) before and after 14 days of therapy and clinical status (hypotension, increased heart rate and respiratory rate, and ascites) every 2 days. Controls (distilled water (5 ml/kg, i.g., once daily) or drinking water (2 ml/mouse per day) given throughout 14 days) exhibited additionally increased BET-1 and aggravated clinical status, while enzyme values maintained their initial increase. BPC157 (10 microg/kg) and amlodipine treatment reversed the increased BET-1 (rats, mice), AST, ALT, CK (rats, mice), and LDH (mice) values. BPC157 (10 ng/kg) and losartan opposed further increase of BET-1 (rats, mice). Losartan reduces AST, ALT, CK, and LDH serum values. BPC157 (10 ng/kg) reduces AST and ALT serum values. Clinical status of CHF-rats and -mice is accordingly improved by the BPC157 regimens and amlodipine.     

Proteasome inhibitor lactacystin ablates liver injury induced by intestinal ischaemia-reperfusion

1. The aim of the present study was to investigate the role of proteasome in the pathogenesis of liver injury induced by intestinal ischaemia-reperfusion (I/R) and the effect of the proteasome inhibitor lactacystin on neutrophil infiltration, intracellular adhesion molecule (ICAM)-1 and nuclear factor (NF)-kappaB expression in the liver tissues of rats. 2. Thirty-two Wistar rats were randomly divided into four groups (n = 8 in each group) as follows: (i) a control, sham-operated group; (ii) an I/R group subjected to 1 h intestinal ischaemia and 4 h reperfusion; (iii) a group pretreated with 0.2 mg/kg lactacystin 1 h before intestinal I/R; and (iv) a group pretreated with 0.6 mg/kg lactacystin 1 h before intestinal I/R. Liver and intestine histology were observed. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH), as well as 20S proteasome activity in circulating white blood cells, were measured. Myeloperoxidase (MPO) activity in liver tissues and the immunohistochemical expression of liver NF-kappaB and ICAM-1 were assayed. In addition, a western blot of liver NF-kappaB was performed. 3. Compared with the sham-operated control group, liver and intestine injury was induced by intestinal I/R, characterized as histological damage including oedema, haemorrhage and infiltration by inflammatory cells, as well as a significant increase in serum AST (365 +/- 121 vs 546 +/- 297 IU/L, respectively; P < 0.05), ALT (65 +/- 23 vs 175 +/- 54 IU/L, respectively; P < 0.01) and LDH levels (733 +/- 383 vs 1434 +/- 890 IU/L, respectively; P < 0.05). Compared with the control group, MPO activity in the liver tissues increased significantly in the I/R group (2.05 +/- 0.69 vs 3.42 +/- 1.11 U/g, respectively; P < 0.05). Strong positive expression of liver ICAM-1 and NF-kappaB p65 was observed. 4. Compared with the intestinal I/R group, administration of 0.6 mg/kg lactacystin markedly reduced 20S proteasome activity in circulating white blood cells (15.47 +/- 4.00 vs 2.07 +/- 2.00 pmol 7-amino-4-methylcoumarin (AMC)/s per mg, respectively; P < 0.01) and ameliorated liver injury, which was demonstrated by decreased levels of serum AST (546 +/- 297 vs 367 +/- 86 IU/L, respectively; P < 0.05), ALT (175 +/- 54 vs 135 +/- 26 IU/L, respectively; P < 0.05) and LDH (1434 +/- 890 vs 742 +/- 218 IU/L, respectively; P < 0.05) and a reduced liver pathological score (2.13 +/- 0.64 vs 1.25 +/- 0.46, respectively; P < 0.01). Compared with the intestinal I/R group, MPO activity in liver tissues decreased significantly following lactacystin pretreatment (3.42 +/- 1.11 vs 2.58 +/- 0.61 U/g, respectively; P < 0.05) and the expression of liver NF-kappaB and ICAM-1 was markedly ameliorated. 5. The present study reveals that the proteasome inhibitor lactacystin ablates liver injury induced by intestinal I/R. One possible mechanism responsible for this effect is the inhibition of enhanced ICAM-1 and neutrophil infiltration by inhibition of NF-kappaB activity. The results suggest the feasibility of using proteasome inhibitor clinically in the treatment of intestinal I/R.     

Chronic toxic effects of the carbamate pesticide sevin on carbohydrate metabolism in a freshwater snakehead fish, Channa punctatus

The effect of exposure to a sublethal concentration of the carbamate pesticide, sevin (1.05 mg/l), on biochemical parameters of blood, liver and muscle, and enzyme activities in liver, kidney, intestine, brain, gills, and muscles of the freshwater teleost fish, Channa punctatus, was studied after 15, 30 and 60 days. The alterations produced were more marked after 30 and 60 days of exposure than after 15 days; fish were hyperglycaemic and hyperlactacidemic. Glycogen content of liver and muscles decreased, but lactic acid levels of the two tissues increased. In liver, muscles, brain and gills the lactate dehydrogenase (LDH) activity was higher in pesticide-exposed fish in comparison to control fish, but the same enzyme activity was inhibited in kidney and intestine. Decreased pyruvate dehydrogenase (PDH) activity occurred in all six tissues. Succinate dehydrogenase (SDH) activity decreased in muscle at the three time periods and after 30 and 60 days in liver and brain. However, in kidney and intestine the latter enzyme activity was elevated. The results suggest that anaerobic metabolism was favoured and aerobic oxidation of pyruvate was impaired in fish exposed to sevin.     

肝豆状核变性患者血清肝酶谱的分析

目的 了解肝豆状核变性(HLD)患者血清肝酶谱的变化.方法 应用全自动生化分析仪检测477例患者和60例正常对照组血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(GGT)、腺苷脱氨酶(ADA)、5'-核苷酸酶(5'-NT)、总胆汁酸(TBA)、总胆红素(TBIL)、直接胆红素(DBI...     

番茄红素对四氯化碳致小鼠急性肝损伤的保护作用

目的 观察番茄红素对四氯化碳(CC14)引起的小鼠急性肝损伤的保护作用.方法 将小鼠分为正常组、模型组、番茄红素组和阳性药联苯双酯组.番茄红素组和联苯双酯组分别用番茄红素和联苯双酯ig进行预给药干预,正常组和模型组以溶剂0.1％羧甲基纤维素钠ig,连续给药7d后ip CCl4致小鼠急性肝损伤.计算肝脏指数,检测血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)以及肝组织中的超氧化歧化酶(SOD)、丙二醛(MDA)、乳酸脱氢酶(LDH)的水平,并观察肝组织HE染色切片的病理变化.结果 番茄红素能显著降低急性肝损伤小鼠血清ALT、AST活性;升高肝组织匀浆中SOD活力,降低MDA含量和LDH活性;病理切片表明给药组小鼠肝损伤均减轻.结论 番茄红素对CCl4致小鼠急性肝损伤具有保护作用,其机制可能与番茄红素所具有抗脂质过氧化和清除体内过多的氧自由基的作用有关.     

Synthesis of 2,2′-14C-methylene-bis(3,4,6-trichlorophenol) (Hexachlorophene-14C)

Abstract: The activity of some enzymes involved in hepatic function was measured in rats, in vivo, after one week's repeated envenomation with Hornet's (Vespa orientalis) venom sac extract (VSE) and in vitro in monolayers of tissue culture of rat hepatocytes treated with VSE. The maximal serum enzymatic changes observed in vivo were significant: twenty fold rise of alkaline phosphatase (ALP), a 7–8 fold rise of aspartate aminotransferase (AST) and a 4–5 fold rise in alanine aminotransferase (ALP) activity. Also 2–3x increases of both serum lactic dehydrogenase (LDH) and creatine phosphokinase (CPK) were noted. The maximal in vitro changes were observed after six days of daily envenomation. There were five fold rises of the activity of AST in the medium, as well as of two-three fold rises of ALT, ALP and LDH. These changes suggest that Hornet's VSE induces enzymatic changes in the liver after prolonged, repeated exposures. They also exclude a general effect, like shock, that might possibly occur in the intact animal, as the cause of the demonstrated hepatic damage.     

姜黄素对雷公藤甲素肝损伤的保护作用

目的：探讨姜黄素对雷公藤甲素诱导小鼠慢性肝损伤的保护作用。方法：小鼠32只随机均分4组,每组8只。对照组：每天灌胃生理盐水;姜黄素组：每天灌胃姜黄素100 mg·kg-1;雷公藤甲素模型组：每天灌胃雷公藤甲素400μg·kg-1;姜黄素+雷公藤甲素组：每天灌胃雷公藤甲素400μg·kg-1+姜黄素100 mg·kg-1。每天给药1次,连续28 d。检测血清中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆红素（TBIL）、碱性磷酸酶（ALP）和乳酸脱氢酶（LDH）;测定肝组织中超氧化合物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽（GSH）、谷胱甘肽-S-转移酶（GST）和尿苷二磷酸葡萄糖醛酸转移酶1（UGT1）含量。 HE染色观察肝脏病理改变。结果：与雷公藤甲素组相比,联合组的小鼠ALT和ALP有显著的下降（P<0.05）,AST和LDH没有显著性改变,TBIL有明显升高。姜黄素能升高肝组织中GST、GSH、SOD和UGT1含量（P<0.05）,降低肝组织中MDA的含量。病理检查结果也显示联合姜黄素给药改善了雷公藤甲素引起的病理改变。结论：姜黄素能增强雷公藤甲素慢性中毒小鼠体内的抗氧化能力,对小鼠雷公藤甲素慢性肝损伤具有一定的保护作用。     

Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration

In order to evaluate the toxicity of TiO(2) particles, the acute toxicity of nano-sized TiO(2) particles (25 and 80nm) on adult mice was investigated compared with fine TiO(2) particles (155nm). Due to the low toxicity, a fixed large dose of 5g/kg body weight of TiO(2) suspensions was administrated by a single oral gavage according to the OECD procedure. In 2 weeks, TiO(2) particles showed no obvious acute toxicity. However, the female mice showed high coefficients of liver in the nano-sized (25 and 80nm) groups. The changes of serum biochemical parameters (ALT/AST, LDH) and pathology (hydropic degeneration around the central vein and the spotty necrosis of hepatocytes) of liver indicated that the hepatic injury was induced after exposure to mass different-sized TiO(2) particles. In addition, the nephrotoxicity like increased BUN level and pathology change of kidneys was also observed in the experimental groups. The significant change of serum LDH and alpha-HBDH in 25 and 80nm groups showed the myocardial damage compared with the control group. However, there are no abnormal pathology changes in the heart, lung, testicle (ovary), and spleen tissues. Biodistribution experiment showed that TiO(2) mainly retained in the liver, spleen, kidneys, and lung tissues, which indicated that TiO(2) particles could be transported to other tissues and organs after uptake by gastrointestinal tract.     

An insight into the possible protective effect of pyrrolidine dithiocarbamate against lipopolysaccharide-induced oxidative stress and acute hepatic injury in rats

Lipopolysaccharide (LPS) is a major cell wall molecule of Gram-negative bacteria known to stimulate the synthesis and secretion of several toxic metabolites, such as reactive oxygen species. In this study, the effect of pyrrolidine dithiocarbamate (PDTC), an antioxidant with nuclear factor-κB inhibitor activity, was evaluated in LPS-induced oxidative stress and acute hepatic injury in rats. Animals were pretreated for 3 consecutive days with PDTC (200 mg/kg/day, i.p.) or saline and animals were then challenged with LPS (6 mg/kg, i.p.) or saline. Six hours after LPS injection, animals were decapitated and blood and liver samples were collected to assess the chosen biochemical parameters. Saline-pretreated animals challenged with LPS revealed extensive liver damage, as evidenced by increases in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transferase (γ-GT). Also, LPS treatment resulted in significant increases in serum lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α) and nitrite levels. Furthermore, LPS challenge caused oxidative stress as indicated by an increase in hepatic lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) and a decrease in hepatic reduced glutathione concentration (GSH) as well as decreased activities of superoxide dismutase (SOD) and catalase in hepatic tissues. The administration of PDTC prior to LPS challenge resulted in improved liver functions as evidenced by the decline in serum AST, ALT, γ-GT levels and reduction in serum LDH, TNF-α and nitrite levels. Moreover, PDTC reduced the chosen lipid peroxidation marker, TBARS and increased GSH concentration, and SOD and catalase activities in hepatic tissues. These results indicate that PDTC may be a useful pharmacological agent in alleviating LPS-induced oxidative stress and acute hepatic injury.