Dimerumic acid as an antioxidant from the mold, Monascus anka: the inhibition mechanisms against lipid peroxidation and hemeprotein-mediated oxidation

This study aimed to investigate the antioxidant mechanism of dimerumic acid isolated as the active component with a radical scavenging action from the mold Monascus anka, traditionally used for the fermentation of foods. Dimerumic acid inhibited NADPH- and iron(II)-dependent lipid peroxidation (LPO) of rat liver microsomes at 20 and 200 microM, respectively. When ferrylmyoglobin was incubated with dimerumic acid, the myoglobin was scavenged and an electron spin resonance (ESR) signal with nine peaks was observed. The spin adduct was identified as a nitroxide radical by analysis of hyperfine structure. Similar ESR signal was also detected by incubation of dimerumic acid with peroxyl radicals. Thus, it was clarified that the antioxidant action of dimerumic acid is due to one electron donation of the hydroxamic acid group in the dimerumic acid molecule toward oxidants resulting in formation of nitroxide radical.     

慢性乙肝硬化B超图像与胆汁酸、前白蛋白、胆碱酯酶临床价值的研究

目的明确慢性乙肝肝硬化B超分级与肝功指标:胆汁酸(TBA)、前白蛋白(PAB)、胆碱酯酶(CHE)判断肝纤维化分期的价值。方法检测78例经肝活检证实的慢性乙肝肝硬化患者声像图改变与TBA、PAB及CHE水平,并与肝活检组织纤维化分期进行对照研究。结果肝脏病理组织纤维化分为S1 -S4期78例。中代偿期(S1 -S2)38例,失代偿期(S3 -S4)40例。B超诊断符合率,代偿期90.6 %,失代偿期为97.3 %。随着纤维化程度的加重,PAB、CHE逐渐下降,TBA逐渐升高。TBA、CHE与纤维化分期存在良好的相关性(P<0.01) ,PAB与纤维化分期存在较弱的相关性(P<0.05)。结论肝脏B超的声像图改变与TBA、PAB、CHE指标在一定程度上可以提示早期肝硬化。     

alpha 2u-Globulin nephropathy, renal cell proliferation, and dosimetry of inhaled tert-butyl alcohol in male and female F-344 rats.

tert-Butyl alcohol (TBA) has been shown to cause kidney tumors in male rats following chronic administration in drinking water. The objective of the present study was to determine whether TBA induces alpha 2u-globulin (alpha 2u) nephropathy (alpha 2u-N) and enhanced renal cell proliferation in male, but not female, F-344 rats, and whether the dosimetry of TBA to the kidney is gender specific. Male and female F-344 rats were exposed to 0, 250, 450, or 1750 ppm TBA vapors 6 h/day for 10 consecutive days to assess alpha 2u-nephropathy and renal cell proliferation and for 1 and 8 days to evaluate the dosimetry of TBA following a single and repeated exposure scenario. Protein droplet accumulation was observed in kidneys of male rats exposed to 1750 ppm TBA, with alpha 2u-globulin immunoreactivity present in these protein droplets. A statistically significant increase in alpha 2u concentration in the kidney, as measured by an enzyme-linked immunosorbent assay, was observed in male rats exposed to 1750 ppm TBA with a exposure-related increase in renal cell proliferation. Renal alpha 2u concentration was positively correlated with cell proliferation in male rat kidney. No histological lesions or increased renal cell proliferation was observed in female rats exposed to TBA compared to controls. The TBA kidney:blood ratio was higher at all concentrations and time points in male rats compared with female rats, which suggests that TBA is retained longer in male rat kidney compared with female rat kidney. Together these data suggest that TBA causes alpha 2u-N in male rats, which is responsible for the male rat-specific increase in renal cell proliferation.     

病毒性肝炎患者血清总胆汁酸测定及临床意义

目的 探讨血清总胆汁酸（TBA）测定在病毒性肝炎诊断中的价值。方法 用酶比色法对213例病毒性肝炎患及30例正常对照进行测定，并对结果进行统计处理。结果 正常对照组TBA为11.11±3.64umol/L。病毒性肝炎组急性期（或活动期）的TBA与正常对照组相比差异均有显（P＜0.01）各组中急性期（或活动）与恢复期相比差异亦具有显性（P＜0.01），在恢复期组中，慢性肝炎中度及肝硬变组与急性黄疸期比较差异具有显性（P＜0.05）。结论 血清TBA的含量与肝病的病变相关，对肝炎的诊断，预后判断及辅助鉴别诊断具有一定的价值。     

Antihyperglycemic and antioxidative potential of Psidium guajava fruit in streptozotocin-induced diabetic rats

Psidium guajava Linn. (family Myrtaceae; PG) is a tropical fruit with a blood-glucose-lowering effect in diabetic rats, but its mechanism of action is still unknown. We investigated the antihyperglycemic efficacy and mechanisms of action of PG in streptozotocin (STZ)-induced diabetic rats. After 4 weeks of PG supplementation (125 and 250 mg/kg), PG significantly restored the loss of body weight caused by STZ and reduced blood glucose levels in a dose-dependent manner compared with that in diabetic control rats. Mechanistically, PG protected pancreatic tissues, including islet β-cells, against lipid peroxidation and DNA strand breaks induced by STZ, and thus reduced the loss of insulin-positive β-cells and insulin secretion. Moreover, PG also markedly inhibited pancreatic nuclear factor-kappa B protein expression induced by STZ and restored the activities of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase. We conclude that PG has a significant antihyperglycemic effect, and that this effect is associated with its antioxidative activity.     

妊娠晚期检测血清总胆汁酸的临床意义

目的探讨妊娠晚期检测总胆汁酸的临床意义。方法将400例妊娠晚期孕妇按总胆汁酸值的高低分为观察组(总胆汁酸值>20μmol/L,n=125)和对照组(总胆汁酸值≤20μmol/L,n=275),比较两组孕妇的妊娠结局。结果观察组胎儿窘迫及早产儿的发生率高于对照组,两组比较差异有统计学意义(P<0.01),两组宫内发育迟缓、新生儿中度窒息及产后出血的发生率比较差异无统计学意义(P>0.05)。结论血清总胆汁酸增高是妊娠期肝内胆汁淤积症早期诊断的敏感指标,加强对血清总胆汁酸的检测,有助于妊娠期肝内胆汁淤积症的早期诊断。从而为早期选择合适的分娩方式以及预防胎儿窘迫和早产的发生提供依据。     

血清TBA、ALP联合测定在妊娠期肝内胆汁淤积症诊断中的意义

探讨血清TBA、ALP联合测定在妊娠期肝内胆汁淤积症（ICP）诊断中的临床应用价值,对60例正常孕妇及47例ICP孕妇,分别使用全自动生化分析仪和R IA法检测其血清TBA、ALP、CG含量。结果表明,ICP孕妇组血清TBA、ALP水平显著高于正常孕妇组,且与CG检测结果相关性较好（P〈0.05）。妊娠期妇女TBA、LAP水平是反映ICP的良好指标,与血清CG具有较好的相关性,并且其生化自动化检测方法相对于放射免疫测定CG更为简单、快捷,有利于临床实验室的广泛应用。     

Inhibitory effect of Lysichiton camtschatcense extracts on Fe2+/ascorbate-induced lipid peroxidation in rat kidney and brain homogenates

Lysichiton camtschatcense is a well-known plant in Japan where it has been used as a traditional medicine by the “Ainu” people for the treatment of acute nephritis. It is presumed that L. camtschatcense has an inhibitory effect against nephritis caused by reactive oxygen species (ROS) owing to its antioxidant activities. Consequently, the antioxidant effect of L. camtschatcense extracts was assessed against Fe²⁺/ascorbic acid (AsA)-induced lipid peroxidation in rat kidney and brain homogenates. The antioxidant effect of the chloroform extract (CE) was more potent than that of the methanol extract (ME) for both homogenates. The antioxidant effect of both extracts was similar to those of α-tocopherol, a lipid-soluble antioxidant, and glutathione (GSH), a water-soluble antioxidant, which were used as reference compounds. Although CE showed a low radical-scavenging effect for superoxide anion radicals (O₂^·−) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, assessed by using an electron spin resonance (ESR) method, hydroxyl radicals (·OH) were markedly scavenged by more than 80%. On the other hand, ME showed more significant scavenging effect for DPPH radicals and O₂^·− than CE. These results suggest that the inhibitory effects of the L. camtschatcense extract on lipid peroxidation in rat kidney and brain are based on its high radical-scavenging effect against ·OH, O₂^·−, and lipid-derived radicals generated from the cell membrane.     

Gel entrapment culture of rat hepatocytes for investigation of tetracycline-induced toxicity

This paper aimed to explore three-dimensionally cultured hepatocytes for testing drug-induced nonalcoholic steatohepatitis. Gel entrapped rat hepatocytes were applied for investigation of the tetracycline-induced steatohepatitis, while hepatocyte monolayer was set as a control. The toxic responses of hepatocytes were systematically evaluated by measuring cell viability, liver-specific function, lipid accumulation, oxidative stress, adenosine triphosphate content and mitochondrial membrane potential. The results suggested that gel entrapped hepatocytes showed cell death after 96 h of tetracycline treatment at 25 μM which is equivalent to toxic serum concentration in rats, while hepatocyte monolayer showed cell death at a high dose of 200 μM. The concentration-dependent accumulation of lipid as well as mitochondrial damage were regarded as two early events for tetracycline hepatotoxicity in gel entrapment culture due to their detectability ahead of subsequent increase of oxidative stress and a final cell death. Furthermore, the potent protection of fenofibrate and fructose-1,6-diphosphate were evidenced in only gel entrapment culture with higher expressions on the genes related to β-oxidation than hepatocyte monolayer, suggesting the mediation of lipid metabolism and mitochondrial damage in tetracycline toxicity. Overall, gel entrapped hepatocytes in three-dimension reflected more of the tetracycline toxicity in vivo than hepatocyte monolayer and thus was suggested as a more relevant system for evaluating steatogenic drugs.     

Glycyrrhizic acid modulates t-BHP induced apoptosis in primary rat hepatocytes

Glycyrrhizic acid (GA) is the main bioactive ingredient of licorice (Glycyrrhiza glabra). The object of this study was to evaluate the protective effects of GA on tert-butyl hydroperoxide (t-BHP) induced oxidative injury leading to apoptosis in cultured primary rat hepatocytes. Throughout the study silymarin was used as positive control. Molecular mechanisms involved in apoptotic pathways induced in hepatocytes by t-BHP at 250 μM were explored in detail. DNA fragmentation, activation of caspases and cytochrome c release were demonstrated. In addition, changes in the mitochondrial membrane potential and ROS generation were detected confirming involvement of mitochondrial pathway. Pre-treatment with GA (4 μg) protected the hepatocytes against t-BHP induced oxidative injury and the results were comparable to the pre-treatment with positive control, i.e. silymarin. The protective potential against cell death was achieved mainly by preventing intracellular GSH depletion, decrease in ROS formation as well as inhibition of mitochondrial membrane depolarization. GA was found to modulate critical end points of oxidative stress induced apoptosis and could be beneficial against liver diseases where oxidative stress is known to play a crucial role.