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1.
Physiol Res ; 64(Suppl 5): S627-36, 2015.
Article in English | MEDLINE | ID: mdl-26674288

ABSTRACT

In vitro models serve as a tool for studies of steatosis. Palmitic and oleic acids can induce steatosis in cultured hepatocytes. The aim of our study was to verify steatogenic and cytotoxic effects of palmitic acid (PA), oleic acid (OA) and their combinations as well as their impact on functional capacity of rat primary hepatocytes. Hepatocytes were exposed to OA or PA (0.125-2 mmol/l) or their combination at ratios of 3:1, 2:1 or 1:1 at the final concentrations of 0.5-1 mmol/l. Both OA and PA caused a dose-dependent increase in triacylglycerol content in hepatocytes. PA was more steatogenic at 0.25 and 0.5 mmol/l while OA at 0.75 and 1 mmol/l. PA exhibited a dose-dependent cytotoxic effect associated with ROS production, present markers of apoptosis and necrosis and a decrease in albumin production. OA induced a damage of the cytoplasmic membrane from 1 mM concentration. Mixture of OA and PA induced lower cytotoxicity with less weakened functional capacity than did PA alone. Extent of steatosis was comparable to that after exposure to OA alone. In conclusion, OA or combination of OA with PA is more suitable for simulation of simple steatosis than PA alone.


Subject(s)
Hepatocytes/drug effects , Non-alcoholic Fatty Liver Disease/chemically induced , Oleic Acid/toxicity , Palmitic Acid/toxicity , Albumins/metabolism , Animals , Apoptosis/drug effects , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Hepatocytes/metabolism , Hepatocytes/pathology , Male , Membrane Potential, Mitochondrial/drug effects , Mitochondria, Liver/drug effects , Mitochondria, Liver/metabolism , Mitochondria, Liver/pathology , Necrosis , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Primary Cell Culture , Rats, Wistar , Reactive Oxygen Species/metabolism , Triglycerides/metabolism
2.
J Physiol Pharmacol ; 66(6): 863-73, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26769836

ABSTRACT

The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor, important for combating electrophilic and oxidative stress in the liver and other organs. This encompasses detoxification of hepatotoxic drugs, including acetaminophen (APAP). Recently, an association between apolipoprotein E (ApoE) genotype and Nrf2 expression was described. We compared the toxicity of APAP on primary culture hepatocytes isolated from transgenic mice carrying two different human ApoE alleles and wild-type controls. The cells were exposed to APAP in concentrations from 0.5 to 4 mM for up to 24 hours. APAP led to a dose-dependent hepatotoxicity from 1 mM after 16 h exposure in all mice tested. The toxicity was higher in hepatocytes isolated from both transgenic strains than in wild-type controls and most pronounced in ApoE3 mice. Concurrently, there was a decline in mitochondrial membrane potential, especially in ApoE3 hepatocytes. The formation of reactive oxygen species was increased after 24 hours with 2.5 mM APAP in hepatocytes of all strains tested, with the highest increase being in the ApoE3 genotype. The activity of caspases 3 and 7 did not differ among groups and was minimal after 24 hour incubation with 4 mM APAP. We observed higher lipid accumulation in hepatocytes isolated from both transgenic strains than in wild-type controls. The expression of Nrf2-dependent genes was higher in ApoE3 than in ApoE4 hepatocytes and some of these genes were induced by APAP treatment. In conclusion, transgenic mice with ApoE4 and ApoE3 alleles displayed higher susceptibility to acute APAP toxicity in vitro than wild-type mice. Of the two transgenic genotypes tested, ApoE3 allele carriers were more prone to injury.


Subject(s)
Acetaminophen/toxicity , Analgesics, Non-Narcotic/toxicity , Apolipoproteins E/genetics , Hepatocytes/drug effects , Alleles , Animals , Cells, Cultured , Female , Gene Expression/drug effects , Genotype , Glutathione/metabolism , Hepatocytes/metabolism , Hepatocytes/physiology , Lipid Metabolism/drug effects , Membrane Potential, Mitochondrial/drug effects , Mice, Inbred C57BL , Mice, Transgenic , NF-E2-Related Factor 2/genetics , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism
4.
Cas Lek Cesk ; 143(11): 766-9; discussion 770, 2004.
Article in Czech | MEDLINE | ID: mdl-15628573

ABSTRACT

BACKGROUND: Measurements of anthropometric parameters are widely used in clinical practice as a convenient index of intraabdominal fat. The paper is aimed to reveal correlations between ultrasound measurement of intraabdominal depth (IAAT) and selected anthropometric and biochemical parameters in childhood. METHODS AND RESULTS: In 69 obese children (38 boys, BMI28.3+/-3.2, aged 12.8+/-0,52 and 31 girls with BMI27.4+/-5.02, 12.4+/-0.51), anthropometry, IAAT and laboratory tests were evaluated. Height, weight, BMI, waist and hip circumferences, 10 skinfolds and blood pressure were measured. Blood glucose, uric acid, lipids, inzulín and C-peptide levels were determined. Pearson's partial correlation coefficients after adjusting for age were calculated. In boys, the following significant correlations of IAAT were revealed: with BMI (r=0.44, p<0.06), chest (r=0.45, p<0.005) and hip (r=0.65, p<0.0001) circumferences, waist/hip ratio (WHR, r=0.61, p< or =0.0001), subscapular (r=0.45, p< or =0.005), axillary (r=0.55, p<0.0004), suprailiac (r=0.51, p< or =0.001) and abdominal (r=0.54, p=0.0004) skinfolds. However, among biochemical indexes only triglyceride level was associated with IAAT (r=0.41, p< or =0.01). In girls, the following significant correlations of IAAT were observed: with BMI (r=0.42, p< or =0.01), chest (r=0.42, p< or =0.01) and waist (r=0.46, p<0.009) circumferences, subscapular (r=0.46, p<0.009) and abdominal (r=0.52, p<0.003) skinfolds. In girls, no significant correlation of IAAT with WHR and metabolic parameters was found. CONCLUSIONS: IAAT in children is associated with anthropometric indexes of body fat distribution and in boys also with serum triglyceride level.


Subject(s)
Abdomen/diagnostic imaging , Adipose Tissue/diagnostic imaging , Obesity/diagnostic imaging , Adolescent , Anthropometry , Child , Female , Humans , Male , Obesity/metabolism , Ultrasonography
5.
Bratisl Lek Listy ; 91(8): 658-63, 1990 Aug.
Article in Slovak | MEDLINE | ID: mdl-2207739

ABSTRACT

The paper presents a survey of the incidence of notified malignant intraocular tumors, code 190 of the International Classification of Diseases (ICD-9). It analyzes the incidence, aspecific incidence and mortality rate also according to the 4th subclass of code 190 (ICD-9), covering the territory of the Slovak Republic in the period from 1968-1985. The incidence of intraocular tumors over the period studied was found to be 8.2/100,000 inhabitants. The recorded data correspond to values given for other regions.


Subject(s)
Eye Neoplasms/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Czechoslovakia/epidemiology , Eye Neoplasms/mortality , Female , Humans , Male , Middle Aged , Prevalence
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