Mutual anti-oxidative effect of gossypol acetic acid and gossypol–iron complex on hepatic lipid peroxidation in male rats

Gossypol displays anticancer behavior and anti-fertility in males. Male rats were treated with either gossypol acetic acid (GAA) or gossypol–iron complex (GIC). Serum alanine transaminase (ALT) activity elevated of GAA. However, GIC-treated animals showed a decrease in hepatic glutathione (GSH) content with increased malondialdehyde (MDA) content. Whereas, GSH-Px specific activity increased in GAA group. GAA and GIC induce significant increases in the hepatic NEFA with remarkable decrease in the total saturated fatty acids with a significant increase of PUFA.     

In vitro effect of n-nitrosodiethylamine on lipid peroxidation and antioxidant system in human erythrocytes

Human erythrocytes were used in vitro to investigate the effect of the hepatocarcinogen N-nitrosodiethylamine (NDEA) on lipid peroxidation (LPO) and antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR). LPO and erythrocyte haemolysis increased with increasing concentrations of NDEA and with increased exposure time. CAT activity decreased while GR activity increased with both the increasing concentrations of NDEA treatment and exposure time. However, no alteration was observed in SOD enzyme activity. The inhibitory effects of antioxidants and free radical scavengers such as EDTA, succinic acid, sodium benzoate and ascorbic acid were observed. These agents lowered NDEA-induced LPO and haemolysis in erythrocytes. This might indicate that the generation of free radicals and subsequent LPO may play a role, at least in part, in inducing NDEA toxicity.     

肝病患者血清前白蛋白测定的临床意义

目的 通过测定急、慢性乙型病毒性肝炎和肝硬化不同肝病患者血清中前白蛋白、白蛋白、总胆汁酸含量及凝血酶原活动度，探讨上述不同指标在判定肝脏功能，指导临床治疗中的意义。方法 健康对照组20例（A组）；急性无黄疸型乙肝20例（B组）；急性黄疸型乙肝20例（C组）；慢性乙肝20例（D组）；肝硬化患者20例（E组）。所有被检对象均在清晨空腹静脉采血，用ELISA法测定，试剂盒分别由上海海军医学研究所和南京军区总医院提供，按说明书严格操作。结果 从急性乙型肝炎到慢性乙型肝炎至乙肝后肝硬化，患者血清前白蛋白逐渐降低（均值（mg／L）A组：240．4；B组：170．6；C组160．1；D组：120．8；E组：76．1）。急、慢性乙型肝炎明显降低（P〈0．05）。乙肝后肝硬化显著下降（P〈0．01）。TBA急、慢性乙型肝炎，乙肝后肝硬化组与对照组比较有显著性差异（P〈0．05）。而白蛋白、PT仅肝硬化组与对照组比较有显著性差异（P〈0．05）。结论 血清前白蛋白（Preaibumirk PA）含量的改变能敏感、特异、快速的反应肝病患者肝脏功能的变化。     

乙肝感染孕妇血清CG、ALT和TBA检测临床意义探讨

探讨乙肝感染孕妇血清CG、ALT和TBA检测的临床意义。选取70例乙肝感染住院孕妇作为试验组,选取同期行产前检查的70例健康孕妇作为对照组,比较两组血清CG、ALT和TBA阳性率差异。试验组血清CG阳性率明显高于对照组,差异具有显著性(P0.05);大三阳组血清CG、ALT和TBA阳性率均明显高于小三阳组,差异具有显著性(P0.05);大三阳组血清CG、ALT和TBA阳性率和小三阳组血清CG阳性率均明显高于对照组,差异具有显著性(P0.05)。血清CG、ALT和TBA均为肝功能检测敏感指标,能够直观反应机体肝功能受损程度,其中CG敏感度更高,能够为临床诊断提供准确依据。     

血清总胆汁酸检测在慢性肝炎中的应用

血清总胆汁酸（TBA）的测定有利于慢性肝炎的监测，且可代替重复进行的活组织检查。近期对肝胆科36例患者的检测分析报告如下：     

疏肝利胆和清热通下法治疗急性胆道感染的临床观察

目的：探讨降低胆道感染病人血清总胆汁酸值,减少胆汁酸的急、慢性毒性作用的方法。方法：根据中医学“六腑以通为用”学说,采用疏肝利胆、清热通下法治疗１０７例胆道感染病人,同时进行ＡＰＡＣＨＥ－Ⅱ评分和血清总胆汁酸值测定,与６４例常规西医治疗病人比较分析。结果：１中西医结合非手术治疗组和手术治疗组的血清总胆汁酸值降低幅度大,降低速度快,与对应的常规西医治疗组相比有显著差异（Ｐ＜００５）。２经治疗后４组的ＡＰＡＣＨＥ－Ⅱ评分均随总胆汁酸值下降而显著降低（Ｐ＜００５）。３中西医结合治疗组并发症的发生率较常规西医治疗组显著降低（Ｐ＜００５）。结论：１中西医结合治疗能有效地降低血清总胆汁酸,减轻胆汁酸的急、慢性毒性作用,减少并发症发生率。２再次证实血清总胆汁酸值对外科疾病严重程度的评估价值。     

UPLC-MS-based serum metabonomics for identifying acute liver injury biomarkers in Chinese miniature pigs

Metabonomics has emerged as an important technology for exploring the underlying mechanisms of diseases and screening for biomarkers. In this investigation, to comprehensively assess metabolite changes in d-galactosamine (GalN)-induced liver injury in Chinese miniature pigs and to increase our understanding of physiological changes in normal and pathological states, we used ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to analyze metabolites and identify biomarkers in serum. Blood samples were collected both from 18 h after GalN treatment group and control group pigs. We performed multivariate analyses on the metabolite profiles to identify potential biomarkers of acute liver injury, which were then confirmed by tandem MS. Based on “variable of importance in the project” (VIP) values and S-plots, four groups of biomarkers were identified – namely conjugated bile acids, lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs) and fatty acid amides (FAAs) – that were present at significantly different levels in the control and GalN-induced groups. LPCs, PCs, and FAAs showed marked decreases in the GalN-treated group, whereas conjugated bile acids in the treated group showed considerable increases. Taken together, our results suggested that obvious metabolic disturbances occur during acute liver injury, which provided novel insights into the molecular mechanism(s) of d-galactosamine (GalN)-induced liver injury, and will facilitate future research and management of liver injury.     

Amiodarone inhibits tocopherol-mediated human lipoprotein peroxidation

It is unknown whether lipoprotein tocopherol-mediated peroxidation (TMP) is influenced by peculiar drug physicochemical properties such as hydrophobicity. Thus, we studied the effect of the extremely hydrophobic agent amiodarone on human non-HDL TMP. The drug, albeit devoid of specific radical-scavenging effects, inhibited TMP at therapeutic concentrations and with an efficiency similar to that of the physiological co-antioxidant ascorbic acid, showing indeed an IC₅₀ of 5 μM. A comparable efficiency was observed with human LDL, and with a pure LDL-VLDL mixture. TMP was also inhibited by other hydrophobic cationic amphiphiles without radical-scavenging activity, namely desethylamiodarone, chlorpromazine, clomipramine, promethazine, promazine, verapamil, bromhexine, propranolol, mepivacaine, metoprolol, tramadol and ranitidine, whose anti-TMP potency was far lower than that of amiodarone and related to drug hydrophobicity degree. Further, TMP was strongly inhibited by butylhydroxytoluene, a lipophilic radical scavenger. Hydrophobic acidic (diclofenac, indomethacin, ibuprofen and ketoprofen) or neutral (n-hexane, anthracene, o-xylene and toluene) compounds could not instead inhibit TMP, indicating a stringent requirement for drug basicity in the pharmacological inhibition of TMP. Amiodarone effectiveness was lowered by lipoprotein α-tocopherol enrichment, suggesting some drug-α-tocopherol interaction and less lipid pharmacological protection at higher α-tocopheroxyl radical generation. Drug anti-TMP activity may so be related to electrostatic and hydrophobic interactions with lipoprotein α-tocopherol and lipid moiety, resulting in decreased radical phase transfer and lipid propensity to undergo radical-driven peroxidation. In conclusions, primarily drug basicity and then hydrophobicity are solely relevant to TMP inhibition. Amiodarone, at therapeutic concentrations, has anti-TMP properties, which could occur in the clinical setting.     

Antifibrotic effects of Artemisia capillaris and Artemisia iwayomogi in a carbon tetrachloride-induced chronic hepatic fibrosis animal model

Ethnopharmacological relevance

Artemisia capillaris and Artemisia iwayomogi, both members of the Compositae family, have been indiscriminately used for various liver disorders as traditional hepatotherapeutic medicines in Korea for many years.

Aim of the study

In this study, the anti-hepatofibrotic effects of Artemisia capillaris and Artemisia iwayomogi were comparatively analyzed using a carbon tetrachloride (CCl₄)-induced liver fibrosis rat model.

Materials and methods

Hepatic fibrosis was induced via a 10-week course of intraperitoneal CCl₄ injections (50% dissolved in olive oil, 2 mL/kg, twice per week). Water extract of Artemisia capillaris (AC) or Artemisia iwayomogi (AI) was orally administered six times per week from the 5th to the 10th week.

Results

AI (50 mg/kg) significantly attenuated the CCl₄-induced excessive release of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in serum (p < 0.05), and hydroxyproline and malondialdehyde (MDA) contents in liver tissue (p < 0.05). Further, AI markedly ameliorated the depletion of total antioxidant capacity (TAC), glutathione (GSH), and superoxide dismutase (SOD) in liver tissue (p < 0.01). Unexpectedly, AC did not exert any effects on the above parameters. Histopathological and immunohistochemical analyses revealed that AI drastically reduced inflammation, necrosis, fatty infiltration, collagen accumulation, and activation of hepatic satellite cells in liver tissue. These changes were not observed with AC treatment. Several critical genes of fibrosis-related cytokines including transforming growth factor beta (TGF-β), platelet-derived growth factor beta (PDGF-β), and alpha smooth muscle actin (α-SMA) were more prominently downregulated by AI compared to AC treatment.

Conclusion

Our results show that AI exerts greater hepatoprotective and anti-fibrotic effects as compared with AC via enhancing antioxidant capacity and downregulating fibrogentic cytokines.