Anna Blázovics

Oxidative Stress in the Liver and Biliary Tract Diseases

Oxidative stress plays an important role in the pathogenesis of toxic liver diseases and of other hepatic alterations. We summarize the pathomechanism of free radical reactions in liver diseases and the results of experimental and clinical observations. Most of the hepatoprotective drugs belong in the group of free-radical scavengers, their mechanism of action involving membrane stabilization, neutralization of free radicals and immunomodulation. We demonstrate the effects of the different drugs used in the therapy of liver diseases in animal experiments and in human clinicopharmacological studies. The scavenger effect of these drugs has been demonstrated in the subcellular fractions of liver cells in animal experiments. In vitro incubation with some hepatoprotective drugs inhibit lectin-induced lymphocyte transformation while others decrease the antibody-dependent, spontaneous, and lectin-induced lymphocytotoxicity. Dihydroquinolin-type antioxidants and silymarin enhanced the superoxide dismutase activity of erythrocytes and lymphocytes. In addition, in a 6-month double-blind clinical trial of patients with chronic alcoholic liver disease, we studied the effects of silymarin therapy on liver function tests, on the parameters characterizing the oxidative stress and immune reaction, on serum procollagen III peptide level, and on liver histology. A wide range of methods was used. The silymarin preparate corrected the altered immune reaction and the decreased superoxide-dismutase activity of erythrocytes and lymphocytes in patients with alcoholic liver cirrhosis. The results indicate that these drugs exert hepatoprotective activity and can improve liver functions in alcoholic patients and in toxic liver diseases. We found a correlation between the bilirubin concentration and lipid peroxidation in cases with toxic liver and biliary tract diseases, and assume that there are two kinds of bilirubin, an antioxidant and a prooxidant form, on the basis of diene conjugates in the bile.

The in vitro effect of Helichrysi flos on microsomal lipid peroxidation

Helichrysum arenarium (L.) Moench has long been known as a medicinal plant in Europe for its cholagogue, choleretic, hepatoprotective and detoxifying activities. Antioxidant properties of its main phenolics, flavonoids may be supposed to be responsible for these effects. The aim of this study was to verify the antioxidant properties of lyophilized water extracts with different polyphenol and flavonoid contents from inflorescences. The effects of natural extracts on microsomal fraction of rat liver were examined. Enzymatically induced lipid peroxidation and NADPH cytochrome c reductase activity in liver microsomes were measured by spectrophotometric methods. Results were compared with the activity of silibinin flavonoid, the main agent of well-known milk thistle (Silybum marianum L.). The natural plant extracts diminish the enzymatically induced lipid peroxidation in a concentration-dependent manner and reduce the cytochrome c dose dependently. The sample with higher polyphenol and flavonoid contents showed more stimulation of NADPH cytochrome c reductase. The lyophilized Helichrysi flos extracts proved to be more effective compared to silibinin in examined concentrations.

The Role of Free Radicals in the Pathogenesis of Amiodarone Toxicity

Free Radicals and Amiodarone Toxicity. Introduction: In vitro and in vivo studies were performed to elucidate the pathogenesis of amiodarone toxicity.

In vitro antioxidant properties of Helichrysum arenarium (L.) Moench

The choleretic, hepatoprotective and detoxifying activities of the inflorescence of Helichrysum arenarium (L.) Moench (everlasting, immortelle: Asteraceae-Helichrysi flos syn. Stoechados flos) have been known for a long time from herbal medicine in Hungary. Antioxidant properties of its main phenolics, flavonoids, are supposed to be responsible for these effects. The aim of this study is to verify the antioxidant properties of the lyophilized water extracts from inflorescences, and to define the total polyphenol and flavonoid contents in Helichrysi flos water extracts as well as in lyophilized water extracts. The hydrogen-donating ability and the reducing power property of the lyophilizates were determined spectrophotometrically; their OH&z.rad; scavenging activity was measured, in the H(2)O(2)/OH&z.rad;-luminol-microperoxidase system, by a chemiluminometric method. Results were compared with the activity of the flavonoid silibinin, the main agent of the well-known milk thistle (Silybum marianum L.).

In vitro antioxidant activity of Anthriscus cerefolium L. (Hoffm.) extracts.

Standardised aqueous extracts of chervil (Anthriscus cerefolium L. Hoffm.) (Apiacae) were investigated for antioxidant effect. Numerous in vitro test methods were used to determine whether the extracts, from different vegetative parts (root, herb) had H-donor, metal binding, reductive, free radical scavenging and membrane protective activity. Apiin was used as a reference material. The herb extract showed better activity in all experiments than the root extract. The present results underline that the wateric chervil extracts have antioxidant and anti-lipoperoxidant activity.

Antioxidant and free radical scavenging properties of squeezed juice from black radish (Raphanus sativus l. var niger) root

The in vitro antioxidant properties of squeezed juice from black radish root were investigated by spectrophotometry and luminometry. The sample exhibited strong hydrogen‐donating ability, reducing power, copper(II)‐chelating property and showed a radical scavenging effect in a H2O2/˙OH‐luminol system that points to significant participation in an antioxidant process. According to the HPLC analyses the main active compounds in the juice are not the glucosinolates but probably their degradation products formed by myrosinase hydrolysis. Since a significant amount of polyphenols could be detected in the juice, these compounds could be responsible for the beneficial effect. Copyright

Special wound healing methods used in ancient egypt and the mythological background.

The Egyptian civilisation is one of the oldest in history and was renowned for its scientific and artistic achievements, and medicine was no exception. The ancient Egyptians were masters in applying and arranging bandages, and they recognized the cardinal signs of infection and inflammation. Egyptian drug therapy can be regarded as having evolved from a system rooted in magic and empirical observation. To illustrate how the Egyptian wound healing methods provided a major stimulus for the development of surgery, we conducted a literature search.RésuméLa civilisation d’Egypte est une des plus anciennes de l’histoire et reconnue pour ses accomplissements scientifiques et artistiques: la médecine n’a pas été une exception. Les égyptiens ont bríllés particulièrement en matière d’application et de soins par les pansements; ils reconnaissaient les signes cardinaux de l’infection et de l’inflammation. La thérapeutique médicamenteuse des égyptiens peut être regardée comme ayant évolué à partir d’un système dont les racines relevaient à la fois de la magie et de l’observation empirique. Afin d’illustrer comment la méthode de cicatrisation des égyptiens était un stimulus majeur dans le développement de la chirurgie, nous avons mené une recherche bibliographique.ResumenLa civilización egipcia es una de las más antiguas en la historia de la humanidad y es famosa por sus logros científicos y artísticos, y la medicina no fue excepción. Los antiguos egipcios fueron maestros en la aplicación de vendas, y reconocieron los signos principales de la infección y la inflamación. La terapia farmacológica egipcia se desarrolló a partir de un sistema mágico y de la observación empírica. Hemos realizado una investigación de la literatura con el propósito de ilustrar cómo el método egipcio de cicatrízación de las heridas significó un estímulo mayor para el desarrolló de la cirugía.

Silymarin and vitamin E reduce amiodarone-induced lysosomal phospholipidosis in rats

Several antioxidants have been shown to reduce lysosomal phospholipidosis, which is a potential mechanism of amiodarone toxicity, and prevent amiodarone toxicity by antioxidant and/or non-antioxidant mechanisms. The aim of this study was to test whether the co-administration of two structurally different antioxidants vitamin E and silymarin with amiodarone can reduce amiodarone-induced lysosomal phospholipidosis, and if yes, by reducing the tissue concentration of amiodarone and desethylamiodarone or by their antioxidant action. To this end, male Fischer 344 rats were treated by gavage once a day for 3 weeks and randomly assigned to the following four experimental groups: 1, control; 2, amiodarone (150 mg/(kg per day)); 3, amiodarone (150 mg/(kg per day)) plus vitamin E (100 mg/(kg per day)); 4, amiodarone (150 mg/(kg per day)) plus silymarin (60 mg/(kg per day)) treated groups. Total plasma phospholipid (PL), liver-conjugated diene, thiobarbituric acid reactive substances (TBARSs), amiodarone and desethylamiodarone concentrations were determined and the extent of lysosomal phospholipidosis in the liver was estimated by a semi-quantitative electron microscopic method. Amiodarone treatment increased significantly the liver-conjugated diene (P<0.001), TBARS (P=0.012), plasma total PL (P<0.001) concentrations compared with control. Antioxidants combined with amiodarone significantly decreased the liver-conjugated diene (P<0.001 for both), TBARS (P=0.016 for vitamin E, P=0.053 borderline for silymarin) and plasma total PL (P=0.058 borderline for vitamin E, P<0.01 for silymarin) concentrations compared with amiodarone treatment alone. Silymarin significantly (P=0.021) reduced liver amiodarone, but only tended to decrease desethylamiodarone concentration; however, vitamin E failed to do so. Amiodarone treatment increased lysosomal phospholipidosis (P<0.001) estimated by semi-quantitative electron microscopic method and both antioxidants combined with amiodarone reduced significantly (P<0.001 for both) the amiodarone-induced lysosomal phospholipidosis. In conclusion, silymarin presumably reduced lysosomal phospholipidosis by both antioxidant action and its liver amiodarone concentration decreasing effect, while vitamin E exerted similar effect by antioxidant action alone. Thus, both antioxidant action and inhibition of tissue uptake of amiodarone might have an important role in the preventative effect of antioxidants against amiodarone toxicity.

Free radical scavenging and membrane protective effects of methanol extracts from Anthriscus cerefolium L. (Hoffm.) and Petroselinum crispum (Mill.) Nym. ex A. W. Hill

The antilipoperoxidant activity of Anthriscus cerefolium L. (Hoffm.), chervil, Petroselinum crispum (Mill.) Nym. ex A. W. Hill., parsley extracts were evaluated with ascorbic acid induced lipid peroxidation on rat brain homogenates. These results are completed by the antiradical potential of these extracts against a solution of OH· radical. In all cases luteolin‐7‐O‐glucoside was used as a reference material. Copyright

Effect of silibinin and vitamin E on restoration of cellular immune response after partial hepatectomy

Our aim was to study the antioxidant and immunomodulatory effect of silibinin and vitamin E on the early postoperative course in rats that had undergone a partial hepatectomy (PHX). Male Wistar rats that were treated with silibinin (50 mg/b.w.kg i.p.) and/or vitamin E (500 mg/b.w.kg p.o.) were randomised to undergo 70% PHX. At 72 h after operation, Concanavalin A (Con-A) induced lymphocyte proliferation, and lipopolysaccharide (LPS) induced interleukin-1 (IL-1) mitogenicity and tumour necrosis factor-alpha (TNF-alpha) cytotoxicity were measured in the spleen. In addition, total free radical scavenger capacity of the liver was analysed. In PHX animals, Con-A induced lymphocyte proliferation was significantly decreased, and both LPS induced IL-1 and TNF-alpha activity were significantly increased as compared to Sham treated animals. Treatment with silibinin and vitamin E synergistically restored both lymphocyte proliferation (P<0.01) and cytokine activity (P<0.001) in PHX animals. In addition, silibinin and vitamin E synergistically (P<0.001) restored total hepatic free radical scavenger capacity as well as serum levels of AST and gammaGT, that were all markedly decreased in PHX animals. Our results suggest that preoperative treatment with silibinin and/or vitamin E modulates the cellular immunoresponse and restores impaired liver function following PHX, presumably through their antioxidant capacity. This may explain their beneficial effects on the postoperative course of liver repair.