Serum concentrations of selected adipokines in virus-related liver cirrhosis and hepatocellular carcinoma.

AIM OF THE STUDY: Hepatotropic viruses cause metabolic disturbances such as insulin resistance and hepatosteatosis. Moreover, metabolic factors, such as insulin resistance, obesity, and type 2 diabetes mellitus, increase the risk for hepatocellular carcinoma (HCC) in patients with virus-related liver cirrhosis. Cytokines secreted by the adipose tissue (adipokines) may be implicated in these metabolic disturbances, but there is little evidence regarding the role of adipokines in virus-related cirrhosis and HCC. Thus, we studied whether serum concentrations of selected adipokines were altered in patients with virus-related liver cirrhosis, including patients with HCC. MATERIAL AND METHODS: We included 43 patients with liver cirrhosis due to chronic hepatitis B or chronic hepatitis C. Of these patients, 36 had HCC and 7 did not have any malignant lesions. In addition to routine clinical and laboratory variables, we analyzed serum concentrations of betatrophin, insulin, vaspin, visfatin, and irisin. RESULTS: Compared with healthy controls, patients with HCC had significantly increased vaspin concentrations and significantly reduced irisin concentrations. Compared with controls, patients with virus-related cirrhosis, with or without HCC, had significantly increased concentrations of insulin and betatrophin. The serum visfatin concentration was non-significantly higher in patients with virus-related cirrhosis than in controls. None of the studied adipokines was a significant predictor of HCC. Serum concentrations of the studied adipokines were not related to cirrhosis severity or HCC stage. CONCLUSIONS: Metabolic parameters, including serum adipokine concentrations, are altered in patients with virus-related liver cirrhosis. Adipokines might be related to the HCC risk in these patients.

Serum visfatin and vaspin levels in hepatocellular carcinoma (HCC).

Hepatocellular carcinoma (HCC) is the most common liver cancer, accountable for 90% cases. Visfatin and vaspin are adipocytokines with various suggested functions and proven significant correlations between BMI and percentage of body fat. The aim was to assess visfatin and vaspin serum levels in HCC patients and controls, compare their levels in patients with different cancer etiology and grade assessed according to the Barcelona-Clinic Liver Cancer (BCLC) staging system. The additional aim was to analyze relationship between analyzed adipokines and metabolic abnormalities and liver disfunction severity. The study was performed on 69 cirrhotic patients (54 males/15 females) with HCC, aged 59.0 ± 12.1 years, and with BMI 29.0 ± 4.5 kg/m2 compared to 20 healthy volunteers. Serum visfatin and vaspin concentrations were significantly increased in HCC patients compared to controls (p = 0.01 and p = 0.02, respectively). Serum vaspin was significantly higher in HCC patients with viral compared to those with non-viral etiology (p = 0.02), with more evident increase in chronic hepatitis C patients (CHC). Serum visfatin levels were significantly higher in patients with higher insulin resistance (p = 0.04) and with platelets count > 100 000/mm3 (p<0.001). Patients with BMI >30 kg/m2 had markedly up-regulated vaspin levels (p = 0.04). There was no difference in vaspin and visfatin serum levels with respect to liver dysfunction and BCLC classification. In conclusion, our study revealed serum vaspin and visfatin to be significantly increased in HCC patients independently of cancer etiology compared to controls. Additionally, serum vaspin was elevated in viral disease, especially in CHC. Vaspin up-regulation can be a compensatory mechanism against IR in HCC patients. Serum visfatin and vaspin, although up-regulated, seem not to be associated with cancer grade and cirrhosis severity.

Inhibitory actions of selected natural substances on formation of advanced glycation endproducts and advanced oxidation protein products.

BACKGROUND: Advanced glycation endproducts (AGE) and advanced oxidation protein products (AOPP) arise as a result of excessive glycation and oxidation processes of proteins in hyperglycemia and oxidative stress conditions respectively, both in vivo and in vitro. In vivo these processes are especially intensified in patients with diabetes, and the adverse effects of AGE and AOPP are particularly unfavorable for the pathogenesis and aggravate the biochemical disturbances and clinical complications of diabetes. Total AGE and AOPP (T-AGE and T-AOPP) are heterogeneous groups of compounds, and they can be divided into two main fractions: high- and low-molecular-weight, i.e. HMW-AGE and HMW-AOPP as well as LMW-AGE and LMW-AOPP. Therefore it is important to find natural substances that will prevent formation of total AGE and AOPP and their high- and low-molecular-weight fractions and thereby reduce their adverse effects on tissues and organs. METHOD: Selected natural substances and dietary supplements such as vitamin C, aminoguanidine, quercetin and green tea as well as the multicompound formulations Padma Circosan and Padma 28 were tested in an in vitro model using bovine serum albumin (BSA). Fluorescence of T-, HMW- and LMW-AGE and concentration of T-, HMW- and LMW-AOPP were measured after incubation with these substances. RESULTS: In the examined concentrations quercetin showed the greatest degree of inhibition for T-AGE (60.5 %) as well as for HMW-AGE (79.5 %), while in the case of LMW-AGE the greatest degree of glycation inhibition was shown by Padma Circosan (74.9 %). T-AOPP and HMW-AOPP were best inhibited by vitamin C (87.3 and 89.1 % respectively). The results obtained for LMW-AOPP are atypical, but the lowest concentration was observed in a sample with Padma 28. CONCLUSION: The results show that all tested natural compounds have inhibitory activity towards the formation of total and low- and high-molecular-weight forms of AGE and AOPP in vitro. That suggest a possible role in the prevention of diabetic complications, especially the multiherbal compound Padma preparations, which are especially effective in lowering the most dangerous, i.e. LMW fractions.

The Tibetan herbal medicines Padma 28 and Padma Circosan inhibit the formation of advanced glycation endproducts (AGE) and advanced oxidation protein products (AOPP) in vitro.

BACKGROUND: Advanced glycation endproducts (AGE) and advanced oxidation protein products (AOPP) play a pivotal role in the development of diabetes associated diseases. The herbal medicines Padma 28 and Padma Circosan have shown effectiveness in symptoms of diabetes associated diseases and have antioxidant effects. It is not known whether inhibition of AGE and AOPP formation is a mechanism of their action. METHOD: BSA was subjected to glycation or oxidation with or without 70% ethanolic extracts of Padma 28, Padma Circosan or with an active control. AGE and AOPP concentrations were analyzed fluorimetrically or spectrophotometrically respectively and by ELISA. RESULTS: Compared to the positive control Padma 28, Padma Circosan and the active control significantly reduced AGE levels by 58.6%, 56.7%, and 8.14% (fluorimetry) and by 35.48, 34.19, and 19.68% (ELISA). AOPP were reduced by 57.28/66.78% (30'/60' incubation), by 67.08/71.99%, and by 81.68/86.54% (spectrophotometry) or by 79.98/86.97%, 79.3/84.3% and 77.07/90.31% (ELISA). All results are significantly different (p < 0.001). No difference was found between the effects of the two preparations. CONCLUSION: Both formulas significantly inhibited the formation of AGE and AOPP to a similar extent as the active controls. This suggests a possible role for both Padma preparations in the treatment and prevention of diabetes associated diseases.

[Glycoxidative modification of albumin in medical research]. / Modyfikacje glikooksydacyjne albuminy w badaniach medycznych.

Human albumin is a major, multi-functional serum protein. As the other protein is subjected to many modifications, including glycation and oxidation, which occurs physiologically in low intensity, however, are significantly increased in various pathological conditions. They often co-occur with each other, reinforcing its negative effects, and therefore are referred to common name - glycoxidative processes. Glycation, increased especially in diabetes, causes structural and functional changes of many proteins, both short-and long-lived, and it may result in increased oxidative stress and protein oxidation, which secondarily may increase their susceptibility to glycation. Studies in vivo and in vitro processes of oxidation and glycation of albumin and other proteins allowed us to identify biochemical markers that are routinely used in the diagnosis and monitoring of diseases (ischemia modified albumin, fructosamine) and those commonly used in research (e.g. AGE, CML, SH and CO groups, AOPP), which in perspective could be used in clinical trials (especially AGEs and AOPP). The study presents current state of knowledge on the mechanisms, the importance and the possibility of using glycoxidative modified albumin in medical science.

Advanced glycation end-products and cathepsin cysteine protease in type 2 diabetic patients.

INTRODUCTION: In type 2 diabetes, chronic hyperglycemia induces multi-faceted disturbances and contributes to late diabetic complications. Nonenzymatic glycation, leading to formation of advanced glycation end-products (AGEs), is one of the most important consequences of hyperglycemia. Alterations in the function of some proteolytic enzymes are also observed in diabetes. OBJECTIVES: The aim of the study was to assess the changes in and correlations between the plasma levels of AGEs and the activity of a proteolytic enzyme - cysteine cathepsin B - in plasma and neutrophils derived from patients with type 2 diabetes. PATIENTS AND METHODS: In 102 patients with type 2 diabetes and 55 healthy adults, the plasma levels of total AGEs, low-molecular-weight AGEs (LWM-AGEs), and high­molecular-weight AGEs (HWM-AGEs) as well as cathepsin B activity in plasma and neutrophils were measured by fluorescence methods. Diabetic complications in patients were also evaluated. RESULTS: Diabetic patients had significantly higher levels and activities of all the parameters compared with the control group. Moreover, in these patients, HMW-AGEs correlated negatively with plasma cathepsin B and LMW-AGEs with neutrophil cathepsin B. In the quartiles of the increasing levels of HMW-AGEs and LMW-AGEs, a successive decrease of cathepsin B in plasma and neutrophils, respectively, was observed. In patients with different late diabetic complications only the plasma level of LMW-AGEs was significantly different. CONCLUSIONS: Our study showed a significant increase of all forms of AGEs and corresponding changes in the activity of cathepsin B, both in plasma and neutrophils. A significant correlation between AGEs and cathepsin B as well as the ambiguous character of their alterations in patients with late diabetic complications indicate that they exert a complex effect on the course of diabetes.