Rhabdomyolysis attenuates activity of semicarbazide sensitive amine oxidase as the marker of nephropathy in diabetic rats

Amine oxidases are involved in the progression of many diseases and their complications, including renal failure, due to the generation of the three toxic metabolites (H2O2, aldehydes, and ammonia) in the course of biogenic amines oxidative deamination. The participation of the first two products in kidney pathogenesis was confirmed, whereas the role of ammonia as a potential inducer of the nitrozative stress is not yet understood. The aim of the present study was to test how further intensification of oxidative stress would affect diabetes-mediated metabolic changes. For this purpose, a rat model of glycerol-induced rhabdomyolysis, as a source of powerful oxidative stress due to the release of labile Fe3+ from ruptured myocytes, on the background of streptozotocin-induced diabetes was used. The experimental animal groups were as follows: group 1 – ‘Control’, group 2 – ‘Diabetes’, group 3 – ‘Diabetes + rhabdomyolysis’. A multifold increase in semicarbazide sensitive amine oxidase (SSAO) activity in the kidney and blood, free radicals (FR), MetHb and 3-nitrotyrosine (3-NT) levels in the blood, as well as the emergence of HbNO in plasma and dinitrosyl iron complexes (DNICs) in the liver of animals in group 2 as compared to control were revealed. An additional increase in FR, HbNO levels in the blood, and DNICs in the liver of animals in the diabetes + rhabdomyolysis group as compared to the diabetes group, which correlated with the appearance of a large amount of Fe3+ in the blood of group 3 animals, was detected. Unexpectedly, we observed the positive regulatory effects in animals of the diabetes + rhabdomyolysis group, in particular, a decreased SSAO activity in the kidney and 3-NT level in plasma, as well as the normalization of activity of pro- and antioxidant enzymes in the blood and liver compared to animals of diabetes group. These consequences mediated by rhabdomyolysis may be the result of NO exclusion from the circulation due to the excessive formation of NO stable complexes in the blood and liver. The data obtained allow us to consider SSAO activity as a marker of renal failure in diabetes mellitus. In addition, we suggest a significant role of nitrosative stress in the development of pathology, and, therefore, recommend NO-traps in the complex treatment of diabetic complications

Antitumor efficiency of the natural alkaloid berberine complexed with C₆₀ fullerene in Lewis lung carcinoma in vitro and in vivo

Berberine (Ber) is a herbal alkaloid with pharmacological activity in general and a high anticancer potency in particular. However, due to its low bioavailability, the difficulty in reaching a target and choosing the right dose, there is a need to improve approaches of Ber use in anticancer therapy. In this study, Ber, noncovalently bound to a carbon nanostructure C₆₀ fullerene at various molar ratios of the components, was explored against Lewis lung carcinom

COMPREHENSIVE OVERVIEW OF ADAPTOR PROTEIN RUK/CIN85 ROLES IN CANCER

Aim. This study is focused on a comprehensive overview of mechanisms and processes involved in the acquisition of cancer cell plasticity in a manner dependent on the adapter protein Ruk/CIN85 (in rodents, Ruk — regulator of ubiquitous kinase; in human CIN85 — Cbl-interacting protein of 85 kDa, encoded by SH3KBP1 gene).. Methods. Gene expression was evaluated using RT2-PCR and Western blotting, cell proliferation and survival were analyzed using MTT and/or dye exclusion assays, motility was assessed by scratch test and Transwell assay, enzyme activities were measured using spectrophotometric assays. In vivo metastasis were studies using experimental metastasis model. Conclusion. This study discloses various aspects of cancer cells plasticity, such as EMT, stemness, metabolic changes, ECM components, and drug resistance in dependence on adaptor protein Ruk/CIN85 expression level

Comparison of bioactive aldehydes modifying action on human albumin

Protein’s postsynthetic modifications are a cause and a consequence of many diseases. Endogenous aldehydes are one of the main factors of these modifications formation. The human albumin’s modification under some aldehydes influence in in vitro experiment has been investigated. Human albumin (20 mM) was incubated with following aldehydes: ribose, glyoxal, methylglyoxal and formaldehyde (20 mM each) and their combinations in 0.1 M Na-phosphate buffer (pH 7.4) with 0.02% sodium azide at 37 °C in the dark for up to 30 days. We have determined the fluorescent properties of the samples, the content of protein’s carbonyl groups and the redistribution of protein’s molecular weight. The following ratings of aldehydes from the lowest to the highest effect have been obtained. Fluo­rescent albumin adducts formation: formaldehyde, methylglyoxal, ribose, glyoxal; carbonylation of the protein: ribose, formaldehyde, glyoxal, methyl­glyoxal; polymerization of albumin – the formation of intermolecular crosslinks: ribose, methylglyoxal, glyoxal, formaldehyde. The results indicate that these aldehydes have different capability for protein’s modifications. For example, formaldehyde, having the lowest ability to form fluorescent adducts, shows the highest ability to form protein’s intermolecular crosslinks. Therefore, methods and parame­ters in order to evaluate the protein postsynthetic modification intensity have to be chosen correctly according to carbonyl stress peculiarity in order to evaluate the protein’s postsynthetic modification intensity