Krisztina Hagymási

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.

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.).

Update on the pharmacogenomics of proton pump inhibitors

Proton pump inhibitors (PPIs) are widely used for the treatment of gastroesophageal reflux disease as well as other acid-related disorders. PPIs are metabolized primarily via the CYP2C19 and CYP3A4 isoenzymes; their activity is influenced both by exogenous and endogenous (pharmacogenetic) factors. The CYP2C19 polymorphism affects the metabolism of PPIs, causing large individual pharmacokinetic variations. Differences in the CYP2C19-mediated metabolism can produce marked interpatient variability in acid suppression, in drug-interaction potential and in clinical efficacy. Understanding the pharmacokinetic properties of PPIs and examining the pharmacogenetic alterations may help clinicians optimize PPI therapy and administer individual treatment, especially to nonresponder patients with gastroesophageal reflux disease or ulcer or after failed eradication therapy.

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.

Oxidative damage in alcoholic liver disease

Objective The metabolic effects of alcohol are due both to its direct action and to that of its first metabolite, and can also be connected with the changes in redox state. Differences in ethanol distribution, bioavailability and hepatic metabolism can provide insight into the protective and predisposing factors in alcoholism, as well as gender differences of alcohol toxicity. Oxidative stress occurs following various conditions of ethanol consumption. Design Twenty-six Caucasian patients with alcoholism and 32 healthy, abstinent controls of both sexes were investigated with special regard to reduction–oxidation status and ad hoc free-radical–antioxidant balance. Method Plasma free SH-group concentration, H-donating ability, and reducing power property were measured by simple spectrophotometric methods. Total scavenger capacity was determined by a newly developed chemiluminometric method in plasma and erythrocytes. Results Alcoholics showed a decrease of free SH-group concentration, hydrogen-donating ability and an increase of reducing power property in plasma. A decreased total scavenger capacity of erythrocytes and plasma of alcoholic patients, combined with gender differences, could be detected. Conclusions Alcoholic dependence causes gradual exhaustion of the antioxidant capacity of erythrocytes, therefore this non-invasive measurement may be useful as a follow-up of the evolution of alcoholic liver disease. The results also suggest a gender susceptibility of alcohol toxicity.

The in vitro effect of dandelions antioxidants on microsomal lipid peroxidation.

Dandelions have long been used in herbal medicine for their choleretic, diuretic, antiinflammatory, appetite‐stimulating and laxative properties. An antioxidant property can be supposed as a basis of theirtherapeutic effects. To understand the mechanism of the drugs action, the effects of natural extracts on a microsomal fraction of rat liver were examined. The extracts diminished the enzymatically inducedlipid peroxidation and reduced the cytochrome c with and without NADPH in a concentration dependent manner. Copyright

EPIDEMIOLOGY, RISK FACTORS AND MOLECULAR PATHOGENESIS OF PRIMARY LIVER CANCER

Primary liver cancer is the fifth most common cancer worldwide. Hepatocellular carcinoma accounts for 85-90% of primary liver cancers. Distribution of hepatocellular carcinoma shows variations among geographic regions and ethnic groups. Males have higher liver cancer rates than females. Hepatocellular carcinoma occurs within an established background of chronic liver disease and cirrhosis (70-90%). Major causes (80%) of hepatocellular carcinoma are hepatitis B, C virus infection, and aflatoxin exposition. Its development is a multistep process. We have a growing understanding on the molecular pathogenesis. Genetic and epigenetic changes activate oncogenes, inhibit tumorsuppressor genes, which result in autonomous cell proliferation. The chromosomal instability caused by telomere dysfunction, the growth-retrained environment and the alterations of the micro- and macroenvironment help the expansion of the malignant cells. Understanding the molecular mechanisms could improve the screening of patients with chronic liver disease, or cirrhosis, and the prevention as well as treatment of hepatocellular carcinoma.

Helicobacter pylori infection: New pathogenetic and clinical aspects

Helicobacter pylori (H. pylori) infects more than half of the worlds human population, but only 1% to 3% of infected people consequently develop gastric adenocarcinomas. The clinical outcome of the infection is determined by host genetic predisposition, bacterial virulence factors, and environmental factors. The association between H. pylori infection and chronic active gastritis, peptic ulcer disease, gastric cell carcinoma, and B cell mucosa-associated lymphoid tissue lymphoma has been well established. With the exception of unexplained iron deficiency anemia and idiopathic thrombocytopenic purpura, H. pylori infection has no proven role in extraintestinal diseases. On the other hand, there is data showing that H. pylori infection could be beneficial for some human diseases. The unpredictability of the long-term consequences of H. pylori infection and the economic challenge in eradicating it is why identification of high-risk individuals is crucial.

Role of the endocrine system in the pathogenesis of non-alcoholic fatty liver disease

The most frequent liver disorder in metabolic syndrome is the nonalcoholic fatty liver disease. Its pathogenesis is a complex, multifactorial process, characterized by insulin resistance and involvement of the endocrine system. Hypothyroidism may lead to nonalcoholic steatohepatitis via hyperlipidemia and obesity. Adult patients with growth hormone deficiency have a metabolic syndrome-like phenotype with obesity and many characteristic metabolic alterations. The chronic activation of the hypothalamic-pituitary-adrenal axis results in metabolic syndrome as well. Cushings syndrome has also features of metabolic syndrome. Mild elevation of transaminase activities is commonly seen in patients with adrenal failure. Non-alcoholic steatosis is twice as common in postmenopusal as in premenopausal women and hormonal replacement therapy decreases the risk of steatosis. Insulin resistance, diabetes mellitus type 2, sleeping apnoe syndrome, cardiovascular disorders and non-alcoholic fatty liver disease are more frequent in polycystic ovary syndrome. Hypoandrogenism in males and hyperandrogenism in females may lead to fatty liver via obesity and insulin resistance. Adipokines (leptin, acylation stimulating protein, adiponectin) have a potential role in the pathogenesis of nonalcoholic fatty liver. The alterations of endocrine system must be considered in the background of cryptogenic liver diseases. The endocrine perspective may help the therapeutic approaches in the future.