## 3 Discussion
However, in the context of our study, we have observed that repeated exposure to environmental H2S emitted from thermal spring surroundings has demonstrated a beneficial effect without any apparent negative or toxic consequences. It is important to note that exposure to H2S can indeed lead to various negative effects, which can vary depending on the concentration and duration of exposure. Another noteworthy finding indicates that the levels of lipid peroxidation were lower in all groups exposed to H2S compared to non-exposed groups. This effect was particularly pronounced in the low-ferritin group, demonstrating the crucial role of H2S in conferring a protective effect against lipid peroxidation. These findings align with the previous research where administration of H2S donor NaHS at concentration of 10 and 100 M have a protective effect against lipid peroxidation in plasma samples obtained from healthy individuals pre-incubated with 1 mM homocysteine [33]. This correspondence between our findings and prior studies further supports the notion that H2S possesses significant potential in preventing lipid peroxidation and preserving cellular integrity through its antioxidant properties. The use of various H2S donor systems has shown therapeutic potential [34]. For instance, in a phase II clinical trial (NCT01989208), sodium polythionate (SG1002) is being investigated for its ability to improve plasma H2S levels and lower oxidative stress biomarkers in patients with heart failure [35]. Building upon this knowledge, we explored the possibility that inhalation of H2S released by thermal springs can augment the human body's antioxidant defense system and mitigate oxidative stress. Inhalation of H2S offers a controlled method of delivering H2S over time, bypassing challenges associated with intravenous delivery, such as H2S oxidation and volatilization [36]. Previous studies have established a link between increased levels of lipid peroxides and a decrease in the antioxidant defense system in erythrocytes of anemic patients [37; 38]. Specifically, microcytic patients red blood cells exhibited higher production of malonyl dialdehyde and increase the susceptible to oxidants [39]. In a murine model of IDA, oxidative stress was induced by feeding the animals an iron-deficient diet, further supporting the association between IDA and oxidative stress [26]. H2S has been shown to mitigate plasma lipid peroxidation induced by homocysteine and its thiolactone [20]. By accepting excess electrons, H2S facilitates the formation of disulfide bonds from ROS-initiated oxidation reactions, thereby maintaining thiol-disulfide homeostasis, which is crucial for proper enzymatic antioxidant function [27]. We here highlighted that H2S increase thiol levels endogenously as our study results indicate that individuals with low ferritin levels who experienced periodic exposure to environmental H2S exhibited higher levels of thiol, a crucial antioxidant molecule, and lower levels of oxidative stress. H2S mainly can modulate the activity of many enzymes through \(S\)-sulfhydration modification [2]. Furthermore, H2S acts as a potent protector against carbonyl stress and reduces oxidative stress by \(S\)-sulfhydration of numerous protective proteins [28]. These findings highlight the potential of H2S as a therapeutic agent in mitigating oxidative stress-related pathologies associated with IDA and other conditions. In conclusion, our study demonstrates that inhalation of H2S has a differential effect on oxidative homeostasis depending of the ferritin levels on individuals as illustrated in Figure 6. In individuals with normal ferritin levels, the impact of H2S on oxidative balance is minimal, resulting in a slight increase in thiol concentration. However, in individuals with reduced ferritin levels, H2S exhibits a more pronounced influence. Both H2S and thiol levels show a significant increase, indicating a modulation of the oxidative imbalance.