Isosteviol and its role in cardioprotection: a study on mitochondrial preservation and its relationship with Akt

HERMANN, ROMINA; REZNIK, FEDERICO JOAQUIN; FERNANDEZ PAZOS, MARIA DE LAS MERCEDES; MARINA PRENDES, MARIA GABRIELA; MESTRE CORDERO, VICTORIA; ZAOBONYJ, TAMARA

Ciudad Autonoma de buenos aires

Congreso; VIi International Congress in Translational Medicine organizado por The International Master in Biomedical Sciences (IMBS); 2024

INTERNATIONAL MASTER PROGRAM IN BIOMEDICAL SCIENCES

Background and aims: Isosteviol (Iso) is a derivative of stevioside, one of the main diterpenoid glycosides with sweetening properties that can be obtained from the leaves of Stevia rebaudiana Bertoni. Recent studies have attributed cardioprotective properties to this compound, however, its underlying mechanisms are still not sufficiently elucidated. Given that mitochondrial dysfunction plays a key role in ischemia-reperfusion (Is-Rs) injury, our objective was to investigate the effects of acute pre-ischemic administration of Iso (5 µM) and its relationship with Akt activation on mitochondrial parameters in Langendorff-perfused rat hearts subjected to Is-Rs. Methods: Hearts from female Wistar rats (200-250 g) fed ad libitum were used. Wortmannin (W, 100 nM), a PI3K/Akt inhibitor, was added 15 min before ischemia and 5 min before Iso. Mitochondrial quantity and size were evaluated by electron microscopy, while isolated mitochondrial function was assessed through ATP synthesis rate, O2 consumption, membrane potential (Δψ), and respiratory complex activities I-III, II-III, and IV. Calcium retention capacity (CRC) was measured using the fluorescent dye Calcium Green-5N. Western blot was used to analyze the levels of PGC1α, TFAM, and the Akt activation profile, considering the p-Akt/Total-Akt ratio. ANOVA n=6. Results: At the end of reperfusion period, the results showed an increase in the mitochondrial ATP synthesis rate in the Isosteviol-treated group compared to controls (p