## 3 Results and Discussion
### Hematoprotective Effect of Jabuticaba Wine Extracts  
Jabuticaba wine extracts were evaluated as hematoprotective (antioxidant) agents against the oxidative stress induced by AAPH-derived free radicals. For this, we first determined the half-maximal oxidative concentration (OC\({}_{50}\)) of AAPH. This was an important step since the effective concentration of AAPH reported in previous studies is controversial. Effective concentrations varying from 20 to 200 mM were used to lead erythrocytes to oxidative damage [57; 58; 59; 60; 61]. In the present study, an OC\({}_{50}\) of 7 mM was determined after erythrocyte exposure to AAPH (Figure S2), which allowed a better observation of the oxidative progress and cell lysis. In addition, ascorbic acid maximal (50 uM) and submaximal concentrations (6 uM) were also determined as antioxidant controls (Figure S3). All the extracts displayed antioxidant activity by preventing RBC lysis in a dose-dependent manner (Figure 2). In addition, the partitioning procedure increased the hematoprotective effect of samples. After 4 h exposure to AAPH, we observed that JWF2 and JWF3 were the most active extracts. The maximal hematoprotective effect against oxidative stress was observed at 7.8 and 31 ug/mL, respectively. The result displayed by JWF2 was similar to that for ascorbic acid. The reference antioxidant agent showed maximal hematoprotective effect at 50 uM (8.8 ug\(\cdot\)mL\({}^{-1}\)). The less active extracts, JWE and JWF1, displayed maximal hematoprotective effects at 250 and 62 ug\(\cdot\)mL\({}^{-1}\), respectively. The fruits of different _Plini_ species have been investigated as sources of antioxidants. Previously, [PERSON] et al. (2015) demonstrated that jabuticaba (_M. jaboticaba_) peel powder and its aqueous extract increased the antioxidant mechanisms of Wistar rats, including catalase activity and GSH levels [55]. Recently, extracts derived from _M. cauliflora_ seeds were reported as hematoprotective agents since they were able to attenuate the oxidative damage induced by AAPH on human RBC [57]. Both studies highlighted phenolics, especially flavonoids, as responsible for antioxidant bioactivity. Despite the hematoprotective effect of jabuticaba peels and seeds, it is worth mentioning that the fermentation process enhances the antioxidant properties of plant-based products through the biotransformation of phenolics into more active compounds [62], which turns fermented jabuticaba products (wine or its derived extracts) into an interesting source of bioactives. To the best of our knowledge, this is the first report on the hematoprotective effect of jabuticaba wine-derived extracts. JWF2 and JWF3 were the most effective antioxidant agents. Thus, their effect on RBCs' total antioxidant power was determined from the hematoprotective assay (Figure 3). After the AAPH challenging, JWF3 displayed a similar TCAP level (52 \(\pm\) 3 uM Fe\({}^{2+}\)-ug\({}^{-1}\) protein) to that of untreated cells (52 \(\pm\) 1 uM Fe\({}^{2+}\)-ug\({}^{-1}\) protein). This result suggests that this fraction maintained the intracellular antioxidant status of RBCs. In turn, JWF2 increased the TCAP levels of RBCs when compared to controls and JFW3. A significant difference (\(p\) < 0.05) was observed between this fraction (73 \(\pm\) 10 uM Fe\({}^{2+}\)-ug\({}^{-1}\) protein) and the AAPH-challenged RBCs (40 \(\pm\) 9 uM Fe\({}^{2+}\)-ug\({}^{-1}\) protein). [PERSON] et al. (2022) demonstrated that grape juice and wine (0.15 mL/mL erythrocytes) can protect RBC from oxidative damage by increasing the cellular antioxidant mechanisms (total thiol group amount and catalase activity) and total antioxidant power after 24 h of treatment [63]. Interestingly, jabuticaba peel extract was reported as an inducer of catalase and glutathione s-transferase mRNA expression in muscle cells [64]. Here, we demonstrated that jabuticaba wine-derived fractions, especially JFW2, can protect RBCs from free radical attack and maintain the TCAP at levels that prevent cellular oxidative damage.