Species-specific toxicity of troglitazone on rats and human by gel entrapped hepatocytes

Troglitazone, despite passing preclinical trials on animals, was shortly withdrawn from market due to its severe hepatotoxicity in clinic. As rat hepatocyte monolayer consistently showed sensitive troglitazone toxicity as human hepatocyte monolayer in contrast to the species-specific toxicity in vivo, this paper utilized both hepatocytes in three-dimensional culture of gel entrapment to reflect the species difference on hepatotoxicity. Rat hepatocytes in gel entrapment did not show obvious cellular damage even under a long-term exposure for 21 days while gel entrapped human hepatocytes significantly displayed oxidative stress, steatosis, mitochondrial damage and cell death at a short exposure for 4 days. As a result, the detected species-specific toxicity of troglitazone between gel entrapped rat and human hepatocytes consisted well with the situation in vivo but was in a sharp contrast to the performance of two hepatocytes by monolayer culture. Such contradictory toxicity of rat hepatocytes between monolayer and gel entrapment culture could be explained by the fact that troglitazone was cleared more rapidly in gel entrapment than in monolayer culture. Similarly, the differential clearance of troglitazone in rat and human might also explain its species-specific toxicity. Therefore, gel entrapment of hepatocytes might serve as a platform for evaluation of drug toxicity at early stage of drug development by reducing costs, increasing the likelihood of clinical success and limiting human exposure to unsafe drugs.     

Prophylactic effect of α-linolenic acid and α-eleostearic acid against MeHg induced oxidative stress,DNA damage and structural changes in RBC membrane

The present study was undertaken to evaluate under in vivo condition the effects of α-linolenic acid and α-eleostearic acid against methyl mercury (MeHg) induced oxidative stress. Male albino rats were divided into six groups. Group 1 was under normal control and Group 2 was treated with methyl mercury chloride (MeHgCl; 5 mg/kg BW/day). Groups 3, 4, 5 and 6 were orally treated with different doses of the two fatty acids (0.5% and 1.0% of total lipid given for each kind of linolenic acid isomer) along with MeHgCl (5 mg/kg BW). Comet assay of blood lymphocytes showed that administration of α-linolenic acid reduced DNA damage significantly (P < 0.05). Results also showed that activity of antioxidant enzymes of plasma and brain tissue and total antioxidant capacity in plasma decreased significantly due to oxidative stress generated by MeHgCl. Administration in higher dose of both kind of linolenic acid restored all the activities of the antioxidant enzymes and also reduced lipid peroxidation and increased total antioxidant capacity in plasma. Both kinds of linolenic acid successfully maintained the RBC membrane integrity which was totally disrupted and became flat due to MeHgCl stress. α-Linolenic acid was more efficient antioxidant than α-eleostearic acid against oxidative DNA damage.     

Ameliorating effect of curcumin on sodium arsenite-induced oxidative damage and lipid peroxidation in different rat organs

The present study was conducted to investigate the antioxidative effect of curcumin against sodium arsenite-induced oxidative damage in rat. Animals were divided into four groups, the first group was used as control. Groups 2, 3 and 4 were orally treated with curcumin (15 mg/kg BW), sodium arsenite (Sa, 5 mg/kg BW) and sodium arsenite plus curcumin, respectively. Rats were orally administered their respective doses daily for 30 days. Results showed that Sa increased thiobarbituric acid-reactive substances (TBARS) in plasma, liver, kidney, lung, testes and brain. While, the activities of glutathione S-transferase, superoxide dismutase and catalase and the content of sulfhydryl groups (SH-groups) were significantly decreased in plasma and tissues compared to control. Treatment with curcumin alone reduced the levels of TBARS, while induced the activities of the antioxidant enzymes, and the levels of SH-groups. The presence of curcumin with Sa reduced the induction in the levels of TBARS and induced the decrease in the activities of antioxidant enzymes and the levels of SH-groups. Results indicated that treatment with Sa decreased body weight and increased liver weight compared to control. The presence of curcumin with Sa alleviated its toxic effects. It can be concluded that curcumin has beneficial influences and could be able to antagonize Sa toxicity.     

血清总胆汁酶与部分心脑血管疾病的关系探讨

目的探讨血清总胆汁酸（TBA）与部分心脑血管疾病的关系。方法分别对50例高血压患者、35例冠心病患者、20例中风患者和60例健康人血清中TBA、TC、TG、HDL—C、LDL—C的含量进行检测,以健康人为对照组,将结果进行比对分析。结果对照组、原发性高血压、冠心病和中风组血清TBA值（单位：mmol／L）分别为（5．14±1．87）、（14．7±6．8）、（14．1±6．4）、（13．38±6．36）,组间比较P〈0．01,具有统计学意义。TC分别为（4．12±0．49）、（5．56±0．90）、（5．44±0．84）、（5．66±0．80）;TG分别为（0．80±0．20）、（2．14±1．06）、（1．86±0．90）、（1．94±0．91）;HDL—C分别为（1．44±0．30）、（1．42±0．42）、（1．53±0．34）、（1．54±0．55）;LDL—C分别为（2．14±0．16）、（3．16±0．65）、（3．14±0．74）、（3．01±0．50）。结论血清TBA测定对原发性高血压病、冠心病和中风的诊断具有一定的参考价值。     

肝病患者血清前白蛋白、胆碱酯酶和总胆汁酸测定的临床价值

目的 探讨血清前白蛋白（PA）、胆碱酯酶（CHE）和总胆汁酸（TBA）的测定在肝病诊断中的临床价值。方法检测150例（4组）不同肝病患者和50例正常对照组血清PA、TBA、CHE、ALB、TBIL、ALT的含量,并进行统计学分析。结果各组肝病患者的PA、CHE均显著低于对照组（P〈0．05或P〈0．01）,TBA明显高于对照组（P〈0．01）,且随着肝功能损伤程度的加重,PA、CHE逐渐下降,TBA逐渐升高。各组肝病患者的PA、CHE和TBA的阳性率均明显高于同组的ALB、TBIL、ALT的阳性率。结论联合检测血清PA、CHE和TBA对各型肝炎的早期诊断和预后、早期判断有重要的临床价值。     

血清总胆汁酸、胆碱酯酶及前白蛋白检测在各种肝病诊断中的应用

目的 探讨总胆汁酸(TBA)、胆碱酯酶(CHE)及前白蛋白(PA)在肝病诊断中的临床应用. 方法采用AU-400生化分析仪,对62例健康人和各种肝病患者268例检测TBA、CHE及PA,并对结果进行比较. 结果各种肝病患者血清TBA与对照组相比,除轻度慢性肝炎外,其它各组均显著高于正常对照组(P＜0.01);血清CHE与对照组相比,急性肝炎组、慢性肝炎轻度组和肝癌组差异无统计学意义(P＞0.05),慢性肝炎中、重度组及肝炎后肝硬化组,其含量明显降低(P＜0.01);PA 与对照组比较,除急性肝炎组和慢性肝炎轻度组,其它各组结果均显著低于对照组(P＜0.01). 结论血清TBA、CHE及PA是反映肝脏损害程度的较敏感指标,将其综合评价可提高诊断率,且对肝病鉴别诊断以及预后判断有着重要的临床意义.     

Enzymatically synthesized glycogen reduces lipid accumulation in diet-induced obese rats

Based on a recent study indicating that enzymatically synthesized glycogen (ESG) possesses a dietary, fiber-like action, we hypothesized that ESG can reduce the risk of obesity. In this study, the antiobesity effects of ESG were investigated in a model of diet-induced obesity. Male Sprague-Dawley rats were divided into 4 groups and fed a normal or high-fat diet, with or without 20% ESG, for 4 weeks. Body weight, food intake, lipid deposition in the white adipose tissues and liver, fecal lipid excretion, and plasma lipid profiles were measured. At week 3, the body fat mass was measured using an x-ray computed tomography system, which showed that ESG significantly suppressed the high-fat diet–induced lipid accumulation. Similar results were observed in the weight of the adipose tissue after the experiment. Moreover, ESG significantly suppressed the lipid accumulation in the liver but increased fecal lipid excretion. The plasma concentrations of triacylglycerol and nonesterified fatty acid were lowered after a high-fat diet, whereas the total bile acid concentration was increased by ESG. However, the hepatic messenger RNA (mRNA) levels of enzymes related to lipid metabolism were not affected by ESG. Conversely, the mRNA levels of long-chain acyl-CoA dehydrogenase and medium-chain acyl-CoA dehydrogenase were up-regulated by ESG in the muscle. These results suggest that the combined effects of increased fecal lipid excretion, increased mRNA levels of enzymes that oxidize fatty acids in the muscle, and increased total bile acid concentration in the plasma mediate the inhibitory effect of ESG on lipid accumulation.     

Biological effects of bacterial pigment undecylprodigiosin on human blood cells treated with atmospheric gas plasma in vitro

It is known that some bacterial species are more resilient to different kinds of irradiation due to the naturally developed protective mechanisms and compounds such as pigments. On the other hand, reasoned tissue engineering using plasma remains a critical task and requires very precise control of plasma parameters in order to mitigate its potential detrimental effects. Here we isolated a natural protective agent, microbially produced undecylprodigiosin ((5′Z)-4′-methoxy-5′-[(5-undecyl-1H-pyrrol-2-yl)methylene]-1H,5′H-2,2′-bipyrrole), and investigated its effects on human blood cells independently and in combination with plasma. Two approaches were applied; the first, undecylprodigiosin (UP pigment) was added to the blood cultures, which then were exposed to plasma (pre-treatment); and the second- the blood cultures were exposed to plasma and then treated with pigment (post-treatment). The interactions of plasma and UP pigment with blood cells were investigated by conducting a series of biological tests providing the information regarding their genotoxicity, cytotoxicity and redox modulating activities. The exposure of cells to plasma induced oxidative stress as well as certain genotoxic and cytotoxic effects seen as elevated micronuclei incidence, decreased cell proliferation and enhanced apoptosis. In blood cultures treated with UP pigment alone, we found that both cytotoxic and protective effects could be induced depending on the concentration used. The highest UP pigment concentration increased lipid peroxidation and the incidence of micronuclei by more than 70% with maximal suppression of cell proliferation. On the contrary, we found that the lowest UP pigment concentration displayed protective effects. In combined treatments with plasma and UP pigment, we found that UP pigment could provide spatial shielding to plasma exposure. In the pre-treatment approach, the incidence of micronuclei was reduced by 35.52% compared to control while malondialdehyde level decreased by 36% indicating a significant mitigation of membrane damage induced by plasma. These results open perspectives for utilizing UP pigment for protection against overexposures in the field of plasma medicine.     

胎盘FIC1 mRNA的表达及其与ICP关系的研究

目的通过研究妊娠期肝内胆汁淤积症(ICP)胎盘胆盐载体家族性肝内胆汁淤积相关蛋白-1(FIC1)mRNA的表达,以及母胎血中总胆汁酸(TBA)和甘胆酸(CG)水平的变化,探讨胎盘胆盐载体在ICP胎儿病理机制中的作用。方法纳入ICP患者(ICP组)及正常孕妇(对照组)各20例。采用速率法测定母体静脉、脐静脉血中TBA水平;测定放射免疫法CG水平;RT-PCR法测定胎盘组织中胆盐载体FIC1 mRNA表达;另采用原位杂交法对随机选取的两组各两例胎盘组织进行FIC1 mRNA的定位检测。结果1ICP组母血和脐血中的TBA、CG水平均高于对照组,差异有统计学意义(P<0.05)。ICP组母血中TBA、CG水平均高于脐血(25.77±16.64)μmol/Lvs(8.55±5.48)μmol/L;(3416.09±1986.04)μg/dLvs(821.84±673.17)μg/dL,差异有统计学意义(P<0.05);对照组母血和脐血中TBA水平(3.40±2.51)μmol/Lvs(4.37±3.26)μmol/L、CG水平(342.74±234.88)μg/dLvs(309.32±145.20)μg/dL比较,差异无统计学意义(P>0.05)。2ICP组、对照组胎盘组织中均有FIC1 mRNA的表达,且均定位于合体滋养细胞。ICP组FIC1 mRNA表达量低于对照组(0.76±1.22vs37.28±75.03),差异有统计学意义(P<0.05)。3ICP组和对照组胎盘组织中FIC1 mRNA表达量与母血、脐血中TBA和CG水平均无相关性(r=-0.229~0.163,P>0.05)。结论胎盘FIC1 mRNA表达降低,这可能是导致胎盘对胆汁酸的转运障碍,引起ICP胎儿体内胆淤的因素之一。     

乙型病毒性肝炎临床检验结果分析

目的探讨乙型病毒性肝炎患者临床检验结果。方法选取我院2014年1~10月收治的76例乙型病毒性肝炎患者作为观察组,同时收集同期在我院门诊行健康体检的54例健康人群为对照组。比较两组丙氨酸氨基转移酶(AIT)、门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、谷氨酰基转移酶(GGT)、血清胆碱酯酶(CHE)、白蛋白(ALB)、血清胆醇(CHO)、总胆汁酸(TBA)水平变化。结果两组AIT、AST、ALP、GGT、CHE、ALB、CHO、TBA水平比较,P0.05,差异具有统计学意义。结论乙型病毒性肝炎患者临床检验结果表明,AIT、AST、ALP、GGT、CHE、ALB、CHO、TBA水平均出现异常,可作为临床诊断指标。