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Start Over Creator Froněk, Jiří Date Unknown

4. Cholesterol efflux and macrophage polarization in human adipose tissue

Creator:
Králová, Anna, Bartušková, Hana, Kauerová, Soňa, Janoušek, Libor, Froněk, Jiří, Králová Lesná, Ivana, and Poledne, Rudolf
Format:
počítač and online zdroj
Type:
model:article and TEXT
Subject:
cholesterol efflux, pro-inflammatory macrophages, conditioned media, visceral adipose tissue, and adipocyte size
Language:
English
Description:
The pro-inflammatory status of adipose tissue (AT) has been found to be related to reverse cholesterol transport (RCT) from peritoneal macrophages. However, this finding was made in experimental models using induced peritonitis and isolated peritoneal macrophages of animals. This experimental relationship is in agreement with RCT changes in man in two extreme situations, sepsis or cardiovascular complications. Given the above, we sought to test RTC in relationship to macrophage polarization in the visceral AT (VAT) of living kidney donors (LKDs) and the effect of conditioned media obtained from their AT. The influence of ATCM on CE capacity was first assessed in an experiment where standard plasma was used as cholesterol acceptor from [14C] cholesterol labeled THP-1 cells. Conditioned media as a product of LKDs’ incubated AT showed no effect on CE. Likewise, we did not find any effect of individual plasma of LKDs on CE when individual plasma of LKDs were used as acceptors. On the other hand, we documented an effect of LKDs’ adipose cell size on CE. Our results indicate that the pro-inflammatory status of human AT is not likely induced by disrupted RCT but might be influenced by the metabolic status of LKDs’ adipose tissue.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

5. Pharmacological stimulation of Wnt/beta-catenin signaling pathway attenuates the course of thioacetamide-induced acute liver failure

Creator:
Koblihová, Eva, Mrázová, Iveta, Vaňourková, Zdenka, Maxová, Hana, Kikerlová, Soňa, Husková, Zuzana, Ryska, Miroslav, Froněk, Jiří, and Vernerová, Zdenka
Format:
počítač and online zdroj
Type:
model:article and TEXT
Subject:
acute liver failure, thioacetamide, and Wnt/β-catenin signaling pathway
Language:
English
Description:
Acute liver failure (ALF) is known for extremely high mortality rate, the result of widespread damage of hepatocytes. Orthotopic liver transplantation is the only effective therapy but its application is limited by the scarcity of donor organs. Given the importance in the liver biology of Wnt/β-catenin signaling pathway, we hypothesized that its stimulation could enhance hepatocyte regeneration and attenuate the course of thioacetamide (TAA)-induced ALF in Lewis rats. Chronic treatment with Wnt agonist was started either immediately after hepatotoxic insult (“early treatment”) or when signs of ALF had developed (“late treatment”). Only 23 % of untreated Lewis rats survived till the end of experiment. They showed marked increases in plasma alanine aminotransferase (ALT) activity and bilirubin and ammonia (NH3) levels; plasma albumin decreased significantly. “Early” and “late” Wnt agonist treatment raised the final survival rate to 69 % and 63 %, respectively, and normalized ALT, NH3, bilirubin and albumin levels. In conclusion, the results show that treatment with Wnt agonist attenuates the course of TAA-induced ALF in Lewis rats, both with treatment initiated immediately after hepatotoxic insult and in the phase when ALF has already developed. Thus, the pharmacological stimulation of Wnt/β-catenin signaling pathway can present a new approach to ALF treatment.
Rights:
http://creativecommons.org/publicdomain/mark/1.0/ and policy:public

6. Sex-linked differences in the course of thioacetamide-induced acute liver failure in Lewis rats

Creator:
Koblihová, Eva, Mrázová, Iveta, Vaňourková, Zdeňka, Maxová, Hana, Ryska, Miroslav, and Froněk, Jiří
Format:
počítač and online zdroj
Type:
model:article and TEXT
Subject:
pohlavní rozdíly, sex differences, acute liver failure, thioacetamide, lewis rats, 14, and 612
Language:
English
Description:
Acute liver failure (ALF) is a clinical syndrome with high mortality rate, resulting from widespread hepatocyte damage. Its pathophysiological background is still poorly understood and preclinical studies evaluating pathophysiology and new potential therapeutic measures are needed. The model of ALF induced by administration of thioacetamide (TAA) in Lewis rats is recommended as optimal; however, the limitation of previous studies was that they were performed predominantly in male rats. In view of the growing recognition that sex as a biological variable should be taken into consideration in preclinical research, we examined its role in the development of TAA-induced ALF in Lewis rats. We found that, first, intact male Lewis rats showed lower survival rate than their female counterparts, due to augmented liver injury documented by higher plasma ammonia, and bilirubin levels and alanine aminotransferase activity. Second, in female rats castration did not alter the course of TAA-induced ALF whereas in the male gonadectomy improved the survival rate and attenuated liver injury, reducing it to levels observed in their female counterparts. In conclusion, we found that Lewis rats show a remarkable sexual dimorphism with respect to TAA-induced ALF, and male rats display dramatically poorer prognosis as compared with the females. We showed that testosterone is responsible for the deterioration of the course of TAA-induced ALF in male rats. In most general terms, our findings indicate that in the preclinical studies of the pathophysiology and treatment of ALF (at least of the TAA-induced form) the sex-linked differences should be seriously considered., Eva Koblihová, Iveta Mrázová, Zdenka Vaňourková, Hana Maxová, Miroslav Ryska, Jiří Froněk., and Obsahuje bibliografii
Rights:
http://creativecommons.org/publicdomain/mark/1.0/ and policy:public