ATB 340, A MODULATOR OF SULFITE OXIDASE ACTIVITY, REDUCES OXIDATIVE STRESS IN HYPERGLYCEMIA AND STRESS EXPOSED GASTRIC MUCOSA IN OLD RATS
Introduction. Sulfite oxidase (SO) is one of mitochondrial enzymes involved in H2S-pathway and multiple physiological processes, including oxidative stress. The dominant sulfide oxidation products vary in a tissue-specific manner, whatever SO/oxidative stress involved in gastric mucosa (GM) injury is unclear. Our labs has shown potent cytoprotective and anti-inflammatory effects of H2S-rich compounds, including hybrid nonsteroidal anti-inflammatory drugs (H2S-NSAIDs) but their effects on age-related metabolic dysfunction in GM exposed to long-term postprandial hyperglycemia by high fructose diet (HFD) is still unknown.
Aim. To characterize the activity of sulfite oxidase (SO) and role of oxidative stress in older rats GM exposed to HFD and to assess the therapeutic effect of the recently synthesized H2S donor, hybrid NSAID, H2S-acetylsalicylic acid (H2S-ASA, ATB 340) on adult vs old rat GM.
Material and methods. Adult (n=24) and old (n=43) were divided to control groups with standard diet (SD) and 28-days hypercaloric high-fructose diet (HFD, V. Kozar, 2008) without and with water-immersion stress (WIS) induction (Takagi, 1964). HFD groups on 19-28 day were supplemented per os: a) vehicle (1.0 ml of saline per os),; b) NaHS, 100 μmol/kg/day; c) vehicle and stress induction; d) NaHS, 100 μmol/kg/day and stress induction; e) ASA, 10 mg/kg/day and stress induction; f) conventional aspirin (ASA), 10 mg/kg/day and NaHS, 100 μmol/kg/day and stress induction; g) ATB-340, 17.5 mg/kg/day and stress induction. The integrity of the GM was analyzed by histological scoring based on studies of GM samples. Indicator of oxidative stress, malonic dialdehyde (MDA) and activity of SO in GM were estimated by standard biochemical methods.
Results. We have observed a different SO expression in GM in adult vs old rats with SD and HFD without and with WIS. The effect of HFD resulted in an increase in SO activity in old rats by 15%, whereas in adults by 14%. MDA content changes were similar. In animals that were administered NaHS, adult vs old MDA changes had a similar tendency, while SO activity in older rats was higher in 23%. The stress induction reduced SO activity in old animals by 35%, while in adult ones – by 22%, and the difference in the content of MDA reached 41%. The effect of exogenous NaHS in old rats under stress was highest when combined with ASA, while the MDA content was highest when classical aspirin was used, which coincided with similar changes in HS.
Conclusion. Sulfite oxidase is the essential contributor to age-related oxidative stress in GM that was tested. Supplementation of ATB-340 (H2S-aspirin), which increases the H2S content in the tissues, reduces the symptoms of GM damage associated with a decrease in the activity of SO and the content of MDA, indicating the alleviation of oxidative stress, showing an anti-radical and anti-oxidant effects.
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