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. 2025 Oct 31;44:102327. doi: 10.1016/j.bbrep.2025.102327

Effect of Si-based agent on alcohol hangovers and liver damage caused by acute ethanol overdose

Yoshihisa Koyama a,b,⁎,1, Xin Ye a,1, Yuki Kobayashi c, Ikuei Hirota a, Hikaru Kobayashi c, Shoichi Shimada a,b
PMCID: PMC12617789  PMID: 41244151

Abstract

Excessive alcohol consumption induces hangover symptoms such as headaches, sleep disorders, nausea, cognitive and sensory impairments, depression, and autonomic nervous system dysfunction, as well as liver damage. Additionally, alcohol hangovers cause an altered state of consciousness referred to as intoxication, which may lead to decreased work performance and a higher risk of workplace accidents. Furthermore, liver damage resulting from excessive alcohol consumption has significant health implications. Therefore, developing an effective treatment for alcohol hangovers and alcohol-induced liver damage is highly desirable.

A silicon (Si)-based agent reacts with water to continuously generate a substantial amount of hydrogen. In fact, oral administration of the Si-based agent to mice has been shown to increase hydrogen concentration in the intestine. Reports indicate that hydrogen gas alleviates acute alcohol-induced liver injury, suggesting that the Si-based agent could serve as an effective treatment for excessive alcohol consumption.

This study evaluated the Si-based agent's ability to alleviate motor impairment associated with hangover and prevent ethanol-induced liver damage in acute overdose mouse models. A comparative analysis between the Si-based agent-treated group and untreated group demonstrated that the Si-based agent mitigated reductions in spontaneous activity, behavioral performance, and motor coordination associated with alcohol consumption. Moreover, morphological analysis showed that the Si-based agent-treated group exhibited significantly less ethanol-induced liver damage compared to the untreated group. Aldehyde dehydrase activation showed to persist in the untreated group, but not in the Si-based agent-treated group. Furthermore, in the Si-based agent-treated group, antioxidant capacity exhibited a slight increase after ethanol administration; however, this change did not reach statistical significance.

In conclusion, our findings indicate that the Si-based agent alleviates motor impairment associated with hangover and liver damage by alleviating the increase in oxidative stress and promoting the ethanol metabolize caused by excessive alcohol intake. This study suggests that the Si-based agent has potential as an effective treatment for alcohol hangovers and alcohol-induced liver damage in the future.

Keywords: Alcohol hangover, Si-based agent, Antioxidant, Liver injury

Highlights

  • •

    Si-based agent alleviated hangover symptoms following excessive ethanol intake.

  • •

    Si-based agent reduced liver damage caused by excessive ethanol intake.

  • •

    Si-based agent enhanced antioxidant activity against excessive ethanol intake.

1. Introduction

Alcohol consumption is prevalent in modern society because it stimulates appetite, relieves stress, and facilitates social interaction, but it is also linked to liver diseases such as fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma [[1], [2], [3]]. In particular, alcohol hangovers and inflammatory liver disorders caused by excessive alcohol intake not only compromise individual health but also induce an altered state of consciousness known as intoxication, which can lead to reduced work efficiency and an increased risk of workplace accidents. Therefore, there is an urgent need for effective treatments.

Alcohol hangovers present a variety of symptoms, including headaches, sleep disorders, nausea, cognitive and sensory impairments, depression, and autonomic nervous system dysfunction. Symptomatic treatments typically involve intravenous administration of glucose solutions and oral administration of gastrointestinal medications [4]. There are various theories regarding the mechanisms underlying alcohol hangovers, including mild alcohol withdrawal symptoms [4], acidification of bodily fluids [5], increased inflammatory responses [6], gastrointestinal disorders, oxidative stress [6], changes in hormone secretion (e.g., diuretic effects, dehydration, and hypoglycemic states) [5], and acetaldehyde accumulation [4]. However, the precise mechanism of alcohol hangover development remains unclear, and no definitive treatment has been established.

A silicon (Si)-based agent is a novel antioxidant that reacts with water to continuously produce large amounts of hydrogen, which has antioxidant properties [7]. Oral administration of the Si-based agent has been shown to alleviate pathological conditions in various disease model mice, including Parkinson's disease, ulcerative colitis, and interstitial pneumonia [[8], [9], [10], [11]]. Thus, Si-based agent is a potent antioxidant. Additionally, studies have reported that hydrogen gas can alleviate liver damage caused by acute alcohol consumption [12]. Given that the Si-based agent serves as an effective method for in vivo hydrogen administration [9], it may offer a promising therapeutic approach for alcohol hangovers and alcohol-induced liver damage.

In this study, we investigated whether the Si-based agent is effective in alleviating the physical symptoms of alcohol hangovers and preventing liver damage induced by ethanol overdose using acute ethanol overdose mouse models.

2. Materials and methods

2.1. Ethical statement

All animal experiments were conducted following protocols approved by the Committee of Animal Experiments at Osaka University (approval number 01-072-015) and in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. This study also adhered to the ARRIVE guidelines. Every effort was made to minimize the number of mice used and reduce distress. When food and water intake became challenging, food was placed on the bedding, and supplemental agar jelly was provided. Additionally, if abnormalities or humane endpoints (e.g., difficulty feeding or drinking, respiratory distress, self-inflicted injuries, or rapid weight loss ≥20 % within a few days) were observed, the affected mice were promptly euthanized by intraperitoneal injection of pentobarbital (200 mg/kg).

2.2. Animals

Eight- or nine-week-old C57BL/6J male mice (Japan SLC, Shizuoka, Japan) were used in all experiments. They were maintained under controlled temperature conditions (23–25 °C) and provided free access to water and standard rodent pellet. Mice were administered 30 % (v/v) ethanol (EtOH) in distilled water (DW) (3.8 mg/g body weight; EtOH specific gravity 0.8 equivalent) intraperitoneally (i.p.). Control mice received intraperitoneal injections of DW. The mice were randomly divided into four groups: Con (DW i.p.), Si (DW i.p.), Con-EtOH (EtOH i.p.), and Si–EtOH (EtOH i.p.). Previous reports have shown that changes in emotional behavior associated with alcohol intake are observed up to 20 h after intake [13], so behavioral tests, morphological analyses, and blood tests were performed 20 h after injection.

2.3. Preparation for Si-based agent and specialized diet

Si powder (<45 μm) was obtained by sifting, and a Si-based agent was subsequently produced using the previously described bead-milling method [14]. Specifically, the preparation was performed as follows. A mixed solution of ethanol and high-purity Si particle powder was ground using a physical milling method (bead mill). This process reduced the particle size and yielded a more uniform particle size distribution. The ground mixture was then dried to obtain fine Si particles. To render the particle surface hydrophilic, the Si fine particles were mixed with an aqueous hydrogen peroxide solution and stirred, followed by filtration of the mixture. The Si particles containing residual hydrogen peroxide solution were subsequently mixed with ethanol, stirred, and subjected to centrifugation to separate the solid and liquid phases. Finally, the solid fraction obtained after centrifugation was dried to obtain Si-based agent.

Two specialized diets (Oriental Yeast Co., Ltd., Tokyo, Japan) were prepared as previously described [9]. AIN-93 M served as the control diet. For the Si-based agent-containing diet, AIN-93 M was supplemented with 2.5 % of the Si-based agent. Mice were provided with their respective diets one week before the injection of DW or the 30 % EtOH solution.

2.4. Behavior test

2.4.1. Measurement of spontaneous activity using the Supermax system

Spontaneous activity was individually monitored in a home cage using a Supermex photocell beam system (Muromachi Kikai Co., Tokyo, Japan), as previously described [14]. This system featured paired infrared pyroelectric detectors mounted at the center of the chamber ceiling that served as sensors to detect body heat emitted by each mouse. The total spontaneous activity of the mice was recorded over a 10-min period, digitally converted, and stored. Data analysis was performed using CompACT AMS Ver.3 software (Muromachi Kikai Co.).

2.4.2. Open field test

The experimental setup was prepared as previously described [15]. Spontaneous activity in a novel environment was assessed using an open-field apparatus (Muromachi Kikai Co.), consisting of a square arena (500 mm × 500 mm) enclosed by a 400-mm-high wall. The open-field test began with the placement of the mouse at the center of the apparatus. Mouse movements were tracked, and the total travel distance, average speed, and periods of activity and inactivity during the 10-min test were recorded using the video tracking system software ANY-maze (Muromachi Kikai Co.).

2.4.3. Rotarod test

Forelimb and hindlimb motor coordination and balance were assessed using an accelerating rotarod device (MK-610A; Muromachi Kikai Co.), as previously described [15]. Mice were first placed on a rotating rod (3 cm in diameter) operating at a constant low speed of 4 rotations per minute (rpm) for 30 s to allow habituation to walking. The test began at 4 rpm and gradually accelerated to 30 rpm over a 5-min period. The duration each mouse remained on the rod was automatically recorded. Each mouse underwent two trials in a single test session, and statistical comparisons between groups were made using the average performance across the two trials.

2.5. Tissue sample preparation and Hematoxylin-Eosin stain

Mice were perfused with 4 % paraformaldehyde (PFA) in 0.1 M phosphate buffer (PB) under anesthesia using a combined anesthetic mixture (medetomidine: 0.3 mg/kg, midazolam: 4.0 mg/kg, butorphanol: 5.0 mg/kg). The extracted liver was then immersed in the same fixative at 4 °C overnight. The liver samples were dehydrated through a graded ethanol series and embedded in paraffin (T580, FALMA, Tokyo, Japan) using Clear Plus (FALMA). Thin sections (7-μm thick) were prepared using a rotary microtome and mounted on MAS-coated glass slides (Matsunami Glass, Osaka, Japan). The samples were stored at 4 °C until further processing. The paraffin-embedded sections were deparaffinized in xylene, rehydrated through a graded ethanol series, and stained with Hematoxylin and Eosin solution (FUJIFILM Wako Chemicals Corporation, Osaka, Japan). All stained samples were observed using a Keyence microscope (KEYENCE Corporation, Osaka, Japan). Six micrographs of liver tissue from each individual were analyzed using Adobe Photoshop (Adobe Inc., San Jose, CA) to quantify the damaged area, bleeding area, and total tissue area. Damaged areas were defined as regions where hepatocytes were vacuolated or lost, or where bleeding occurred. Bleeding areas were identified by the presence of red blood cells. The average value across the six images was calculated to determine the percentage of damaged or bleeding tissue for each liver.

2.6. Oxidative stress measurement

Oxidative stress measurement was conducted as previously described [9]. Under deep anesthesia, whole blood was collected from the right atrium of DW-injected mice and acute ethanol overdose mouse models. The blood was centrifuged (3000 rpm, 10 min, 4 °C), and the serum was collected. The serum was stored at −80 °C until further analysis. To assess the serum levels of reactive oxygen species (ROS) metabolites and antioxidant capacity, the levels of ROS metabolite-derived compounds (d-ROMs) and biological antioxidant potential (BAP) were measured using REDOXLIBLA (Wismerll Co. Ltd., Tokyo, Japan). The results of the d-ROM test were reported as arbitrary units (U. Carr), where 1 U. Carr corresponds to 0.8 mg/L of hydrogen peroxide. The BAP value reflected the reducing power of blood, with trivalent iron ion (μM) reduction to divalent iron ions serving as an indicator. Comparative analysis was performed using the d-ROMs value, and BAP value.

2.7. Serum biochemical analysis

Serum samples were obtained by centrifuging whole blood collected from the right atrium at 3000 rpm for 10 min at 4 °C. Acetaldehyde levels, aldehyde dehydrogenase (ALDH) activity, and catalase activity were quantified using the Acetaldehyde Assay Kit (Cat. No. EFAC-100; BioAssay Systems, Hayward, California), Aldehyde Dehydrogenase Assay Kit (Cat. No. EADH-100; BioAssay Systems) and Catalase Assay Kit (Cat. No. ECAT-100; BioAssay Systems) respectively, according to the manufacturer's instructions.

2.8. Statistical analysis

For all studies, one-way ANOVA followed by Tukey's post-hoc test was performed to compare differences between four groups. Statistical significance was defined as follows: ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ∗∗∗∗p < 0.0001. Data are expressed as the mean ± standard error of the mean (SEM).

3. Results

We investigated the effectiveness of the Si-based agent in alleviating motor impairment associated with hangover using acute ethanol overdose mouse models. Twenty hours after ethanol administration, several mice in the control diet (Con-EtOH group) exhibited decreased spontaneous activity compared to the ethanol-untreated mice (Con) (Fig. 1a). Conversely, only one mouse in the Si-based agent-containing diet (Si–EtOH group) showed decreased spontaneous activity compared to the ethanol-untreated mice (Si). One-way ANOVA followed by Tukey's post-hoc test revealed significant differences among the four groups (Fig. 1a; p = 0.0097), with the Si–EtOH group showing significantly higher spontaneous activity than the Con-EtOH group (p = 0.0059), indicating that the administration of the Si-based agent significantly alleviates the decrease in spontaneous activity caused by ethanol administration. To further assess locomotor behavior, we analyzed movement in a novel environment using the open-field test. In one-way ANOVA, significant differences were detected among the four groups in all parameters, including travel distance (Fig. 1b; p < 0.0001), travel speed (Fig. 1c; p < 0.0001), and activity time (Fig. 1c; p < 0.0004). In subsequent Tukey's post-hoc test, 20 h after ethanol administration, the Con-EtOH group showed a significant reduction in travel distance (p < 0.0001), travel speed (p < 0.0001), and activity time (p = 0.0013). In contrast, the Si–EtOH group exhibited a significant increase in travel distance (p = 0.0063), travel speed (p = 0.0058), and activity time (p = 0.013) compared to the Con-EtOH group. The Si-based agent significantly inhibited the decrease in activity under a novel environment caused by ethanol administration. Furthermore, motor coordination and balance function were examined using the rotarod test. One-way ANOVA followed by Tukey's post-hoc test revealed significant differences among the four groups (Fig. 1e; p = 0.0281), and the length of retention time of the Si–EtOH group compared with that of Con-EtOH group (p = 0.0247). The Si-based agent mitigated the EtOH-induced decline in motor coordination.

Fig. 1.

Fig. 1

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(a) Bar graph depicting the average measured value of spontaneous activity. White: Con group, red: Con-EtOH group, grey: Si group, and blue: Si–EtOH group. Data are expressed as the mean ± SEM of six DW-injected mice and ten acute ethanol overdose mouse models per group. ∗∗p < 0.01 vs. Con-EtOH group, determined by one-way ANOVA followed by Tukey's post-hoc test.(b–d) Bar graphs showing (b) average travel distance, (c) average travel speed, and (d) activity time. White: Con group, red: Con-EtOH group, grey: Si group, and blue: Si–EtOH group. Data are expressed as the mean ± SEM of six DW-injected mice and ten acute ethanol overdose mouse models per group. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗∗p < 0.0001 vs. Con or Con-EtOH group, determined by one-way ANOVA followed by Tukey's post-hoc test.(e) Bar graph depicting the retention time in the Rotarod test. White: Con group, red: Con-EtOH group, grey: Si group, and blue: Si–EtOH group. Data are expressed as the mean ± SEM of six DW-injected mice and ten acute ethanol overdose mouse models per group. ∗p < 0.05 vs. Con-EtOH group, determined by one-way ANOVA followed by Tukey's post-hoc test.

Taken together, these results demonstrated that the decline in activity and motor function caused by excessive ethanol intake can be significantly improved by administering a Si-based agent.

Next, we analyzed ethanol-induced morphological changes in the liver, particularly those related to detoxification. In the untreated mice, although minor technical artifacts, such as slight cell atrophy due to 4 % PFA fixation, were observed, no significant morphological abnormalities were detected in either group, and no structural differences were noted between the Con and Si groups (Fig. 2). Subsequently, we examined the livers of acute ethanol overdose mouse models (Fig. 3a and b). In the Con-EtOH group, numerous hepatocytes with prominent vacuolation were observed in the parenchymal region of the liver (Fig. 3c–e). In areas of severe damage, particularly around the interlobular veins, some hepatocytes had detached (Fig. 3e). Conversely, in the Si–EtOH group, only a few hepatocytes exhibited mild vacuolation, and no hepatocytes with extensive vacuolation were observed (Fig. 3b–d). The percentage of damaged areas in the entire liver was found to be significantly reduced in the Si–EtOH group compared to the Con-EtOH group (Fig. 3i). Additionally, hepatic hemorrhage was also assessed. In the Con-EtOH group, cell loss near the interlobular veins in the portal tract area, along with infiltration of red blood cells, was observed (Fig. 3g). Hemorrhaging in the Con-EtOH group was localized within the liver parenchyma, whereas the Si–EtOH group exhibited no cell loss or hemorrhage around the interlobular veins (Fig. 3h). Furthermore, bleeding in the Si–EtOH group was restricted to the capsule side (outermost layer) of the liver parenchyma, with no hemorrhage observed in the deeper parenchymal regions. The number of mice exhibiting hepatic hemorrhage was higher in the Con-EtOH group than in the Si–EtOH group (Fig. 3j). The proportion of hemorrhagic areas relative to total liver tissue was also analyzed. Although the Con-EtOH group exhibited substantial individual variation, the Si–EtOH group showed a trend toward reduced hemorrhage (Fig. 3k). Finally, no morphological changes were observed in the coronary artery branches, lymphatic vessels, or bile ducts in either group.

Fig. 2.

Fig. 2

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(a–h) Representative HE-stained liver images from the Con (a, c, e, g; six mice) and Si group (b, d, f, h; six mice). Images depict the overall liver structure (a, b, e, f) and magnified views of specific hepatic regions (c, d, g, h). (c, d, g, h) Low-magnification images (left panels; scale bar: 100 μm) and high-magnification images (right panels; scale bar: 50 μm) of the hepatic parenchyma (upper panels) and regions surrounding the interlobular veins (bottom panels).

Fig. 3.

Fig. 3

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(a–h) Representative HE-stained liver images from the Con-EtOH (a, c, e, g; six mice) and Si–EtOH group (b, d, f, h; six mice). Images depict the overall liver structure (a, b) and magnified views of specific hepatic regions (c–h). (c–h) Low-magnification images (left panels; scale bar: 100 μm) and high-magnification images (right panels; scale bar: 50 μm) of the hepatic parenchyma (upper panels), regions surrounding the interlobular veins (middle panels), and hemorrhagic areas (bottom panels).(i) Bar graph depicting the percentage of damaged liver area. White: Con-EtOH group, grey: Si–EtOH group. Data are expressed as the mean ± SEM of six acute ethanol overdose mouse models per group. ∗p < 0.05 vs. Con-EtOH group, determined by Student's paired t-test.(j) Bar graph depicting the hemorrhage rate in the liver. White: Con-EtOH group, grey: Si–EtOH group.(k) Bar graph depicting the percentage of hemorrhagic area in the liver. White: Con-EtOH group, grey: Si–EtOH group. Data are expressed as the mean ± SEM of six acute ethanol overdose mouse models per group.

Taken together, these results suggest that the Si-based agent reduces ethanol-induced liver damage and hemorrhage.

Furthermore, to determine whether oxidative stress contributes to ethanol-induced liver damage, oxidative stress levels were assessed using the d-ROMs and BAP tests. one-way ANOVA followed by Tukey's post-hoc test revealed no significant differences in d-ROMs values among the four groups (Fig. 4a; p = 0.815); however, BAP values differed significantly (Fig. 4b; p = 0.0058), with the Si–EtOH group tending to be higher than the Si group (p = 0.0575). The Con-EtOH group showed no tendency for an increase in BAP compared with the Con group (p = 0.2805), suggesting that the Si group was more capable of responding to oxidative stress.

Fig. 4.

Fig. 4

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(a, b) Bar graphs depicting (a) the average d-ROMs value and (b) the average BAP value. White: Con group, red: Con-EtOH group, grey: Si group, and blue: Si–EtOH group. Data are expressed as the mean ± SEM of six DW-injected mice and eighteen acute ethanol overdose mouse models per group. one-way ANOVA followed by Tukey's post-hoc test showed (a) ANOVA: p = 0.815 and (b) ANOVA: p = 0.0058, Tukey's post-hoc test: p = 0.0575 (Si vs Si–EtOH group).(c) Bar graph depicting the average blood acetaldehyde levels. White: Con group, red: Con-EtOH group, grey: Si group, and blue: Si–EtOH group. Data are expressed as the mean ± SEM of six DW-injected mice and eighteen acute ethanol overdose mouse models per group. one-way ANOVA followed by Tukey's post-hoc test showed no significant difference (ANOVA: p = 0.240). (d, e) Bar graphs depicting (d) the average ALDH activity and (e) the average catalase activity. White: Con group, red: Con-EtOH group, grey: Si group, and blue: Si–EtOH group. Data are expressed as the mean ± SEM of six DW-injected mice and eighteen acute ethanol overdose mouse models per group. one-way ANOVA followed by Tukey's post-hoc test showed (d) ANOVA: p = 0.0274, Tukey's post-hoc test: p = 0.0571 (Con-EtOH vs Si–EtOH group) and (e) ANOVA: p = 0.0350, Tukey's post-hoc test: ∗p < 0.05 (Si vs Si–EtOH group).

Finally, using mouse serum, we investigated blood acetaldehyde levels, a metabolic byproduct of ethanol breakdown, as well as the activities of two key enzymes involved in ethanol metabolism—ALDH and catalase. As a result, no significant differences in blood acetaldehyde concentrations were observed between the two groups, regardless of ethanol administration (Fig. 4c: p = 0.240). In addition, ALDH activity was elevated in the Con-EtOH group compared with the Con group, whereas it remained nearly unchanged between the Si and Si–EtOH groups. Although the difference did not reach statistical significance, ALDH activity tended to be lower in the Si–EtOH group than in the Con-EtOH group (Fig. 4d; p = 0.0571). Furthermore, catalase activity showed a statistically significant difference between the Si and Si–EtOH groups, but the difference was minimal, and no differences were observed among the other groups (Fig. 4e).

4. Discussion

In this study, behavioral tests using acute ethanol overdose mouse models revealed that the Si-based agent mitigated declines in spontaneous activity, behavioral performance, and motor coordination. Additionally, the Si-based agent alleviated ethanol-induced liver damage and hemorrhage. Furthermore, in the Si-based agent administration group, there was a tendency for the antioxidant capacity to increase with ethanol intake and the ethanol metabolism to promote. In summary, these findings suggest that the Si-based agent may be effective in treating alcohol hangover symptoms and liver damage associated with acute ethanol overdose.

The cognitive and physical impairments experienced following excessive alcohol consumption are collectively referred to as alcohol hangover symptoms, which begin when blood alcohol concentration approaches zero [16,17]. In humans, alcohol hangovers are characterized by headache, thirst, nausea, vomiting, tremors, diarrhea, drowsiness, fatigue, decreased motor coordination, and cognitive impairment [[18], [19], [20]]. Experimental animal models of alcohol hangover have demonstrated neuromuscular impairment, reduced motor strength, decreased locomotor activity, gait disturbances, slowed exploratory behavior, anxiety-like behaviors, fear-related phenotypes, and depressive symptoms [13,21].

In this study, we also observed decreased spontaneous activity, motor strength, and motor coordination—hallmark symptoms of an alcohol hangover—20 h after ethanol overdose. The Si-based agent mitigated this ethanol-induced decline in motor function (Fig. 1). These results indicate that the Si-based agent alleviates the physical symptoms of alcohol hangover.

Oxidative stress is implicated in alcohol-induced hangover symptoms and ethanol-induced liver damage, and various antioxidants, including l-ascorbic acid [22], l-cysteine [23], N-acetylcysteine [24], and ginseng berry kombucha [25], have been reported to be effective. The Si-based agent is a potent antioxidant that has demonstrated efficacy in mouse models of oxidative stress-related diseases, including Parkinson's disease, interstitial pneumonia, small intestinal ischemia-reperfusion injury, and ulcerative colitis [[8], [9], [10], [11]]. We hypothesized that the Si-based agent, as an antioxidant, could be effective in alleviating motor impairment associated with hangover and evaluated oxidative stress levels in the blood during alcohol hangover. Oxidative stress analysis revealed that blood antioxidant capacity tended to increase in the Si-based agent-treated group following acute alcohol intake. In contrast, no such significant increase was observed in the untreated group (Fig. 4b). This enhanced antioxidant capacity is thought to reflect the elevated oxidative stress induced by ethanol consumption. These findings suggest that the Si-based agent may alleviate systemic oxidative stress, thereby reducing not only hangover symptoms but also liver damage.

Ethanol is primarily metabolized in the liver (>90 %) and converted into acetaldehyde via enzyme pathways such as alcohol dehydrogenase, cytochrome P450 2E1 (CYP2E1), and catalase [26]. Excessive ethanol consumption leads to elevated acetaldehyde levels, which contribute to liver damage [27]. Moreover, the neurotoxicity of acetaldehyde significantly disrupts brain function [28] and contributes to motor impairment [29]. However, 20 h after ethanol administration, no increase in blood acetaldehyde levels was observed, and there were no significant differences among the four groups (Fig. 4c). In contrast, ALDH activity was elevated in the Con-EtOH group but returned to baseline levels in the Si–EtOH group. This finding indicates that acetaldehyde metabolism was still ongoing 20 h after ethanol administration in the Con-EtOH group (Fig. 4d). Conversely, since acetaldehyde levels were comparable between the Con-EtOH and Si–EtOH groups, it is likely that metabolism had already been completed in the Si–EtOH group at this time point. This difference in the timing of metabolic completion may have contributed to the attenuation of motor impairment associated with hangover, as well as the mitigation of liver injury, observed in the Si–EtOH group.

In this study, a tendency toward increased antioxidant activity and promoted ethanol metabolism in the blood was observed in the Si-based agent-treated group following acute excessive alcohol intake. These effects contributed to the alleviation of ethanol-induced motor dysfunction and liver damage. Moreover, as no adverse effects have been reported for the Si-based agent or molecular hydrogen [30], the Si-based agent has potential as an effective therapeutic strategy for alcohol hangovers and acute ethanol intoxication.

Data availability statement

All relevant data are included within this paper.

Author contributions

Yo.K and X.Y. designed the study, analyzed the data, and wrote the paper. Yo.K and I.H. performed behavior tests and immunofluorescent staining. Yu.K. and H.K. developed the method for fabrication of Si-based agent. S.S. supervised this study and provided intellectual directions. Yo.K. and X.Y. were the equally-contributed first author. All authors discussed the findings and commented on this manuscript.

Funding details

This work was supported by Center of Innovation Program (COI Program) Grant Number JPMJCE1310 and SPRING Grant Number JPMJSP2138, JST, Japan.

Declaration of competing interest

The authors report no conflict of interest.

Acknowledgements

This research was supported by the Center of Innovation Program (COI Program, Grant Number JPMJCE1310 and SPRING Grant Number JPMJSP2138, JST Japan. We thank Ms. M. Hasegawa for technical assistance. We would like to thank Editage (www.editage.com) for English language editing and the Center for Medical Research and Education, Graduate School for Medicine, The University of Osaka, for technical support.

Footnotes

Appendix A

Supplementary data to this article can be found online at https://doi.org/10.1016/j.bbrep.2025.102327.

Appendix A. Supplementary data

The following is the Supplementary data to this article:

Multimedia component 1
mmc1.pdf (16.5MB, pdf)

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