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

Abstract

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.

Keywords

• nitrosative stress
• oxidative stress
• renal failure
• rhabdomyolysis
• semicarbazide sensitive amine oxidase
• type i diabetes