Physiological Basis For Novel Drug Hydrogen Sulfide‐Related Therapy Used To Treat Oxidative Stress In The Model Of Fructose‐Induced Injury

Recent extensive research into accelerated aging and age‐related health problems confirmed the key role of metabolic dysfunction in multiple organ functions by overloaded fructose diet. Among important bioregulators of prostaglandin‐independent mechanisms of cytoprotection are sulfur compounds, and the key ones is Hydrogen Sulfide (H2S). However, it is little known about its physiological effects on fructose‐induced gastrointestinal mucosal (GIM) injury. Aim To test the hypothesis whether there is the interplay between H2S catalytic expression and age‐related GIM malfunction and oxidative stress with underlying high fructose diet (HFD), and evaluate effects of ATB 340 [4‐(5‐thioxo‐5H‐dithiol‐3‐yl)phenyl 2‐acetoxybenzoate]. Methods Cystathionine‐γ‐lyase (CSE), cystathionine‐β‐synthase (CBS), and sulfite oxidase (SO) activities in GIM and oxidative stress indicators malonic dialdehyde (MDA) and carbonyl groups of oxide‐modified proteins (COMP) were estimated by standard biochemical methods in adult and old rats with standard diet (SD) and HFD, during stress exposure with vehicle and ATB 340 (17.5 mg/kg per 9 days per os ) treatment. GIM injuries evaluated via histological damage index (DI). EC Approval: Committee on Bioethics of Lviv National Medical University protocol No 4, 23.04.2018. Results Oxidative stress was associated with increased MDA and COMP (р<0,05), and changes in CSE, CBS, fall of SO activities in older vs young rats, while HSD‐induced decline of GIM tolerance and indicators of oxidation were increased (р<0,05), coinciding with decreased SO (р<0,05) expression and DI value of GIM. Preprocessing ATB 340 reduces these description responses of serum MDA and COMP, DI values and increased SO activity (р<0,05) which may be aggravated stress tolerance. Conclusions Physiological basis of GIM injury during aging is associated with SO‐related mitochondrial dysfunction and increased MDA, COMP accumulations. ATB 340 ultimately improves the capacity of oxidative stress tolerance in hyperglycemia in older rats. These findings provide further insights into H2S‐mediated GIM protection and implicate the benefits of using H2S‐based therapies clinically for the treatment of age‐related changes and oxidative stress tolerance. Support or Funding Information We thank Prof. Natalia Zaichko (National Pirogov Memorial Medical University, Vinnytsia, Ukraine), Prof. J. Wallace (Antibes, Canada) for their support of our work. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .