ラクツロースによる腸内細菌発酵を介した水素産生とNrf2活性化が脳虚血再灌流傷害を軽減する
This study examined whether oral lactulose administration could protect against cerebral ischemia-reperfusion (I/R) injury in rats via intestinal bacterial fermentation and hydrogen generation. Using a middle cerebral artery occlusion model in Sprague-Dawley rats, intragastric lactulose significantly elevated breath hydrogen levels. Treated animals demonstrated improved neurological scores, reduced infarct volume on TTC staining, better-preserved neurons on Nissl staining, and fewer TUNEL-positive apoptotic cells. Biochemical analyses revealed decreases in malondialdehyde, caspase-3 activity, 3-nitrotyrosine, and 8-hydroxy-2-deoxyguanosine, alongside increased superoxide dismutase activity. These effects exceeded those of edaravone. RT-PCR and Western blot confirmed upregulation of Nrf2 in brain tissue. Antibiotic co-administration suppressed hydrogen production and abolished the neuroprotective effects, supporting the conclusion that lactulose-derived hydrogen and Nrf2 activation are the principal mediators of the observed protection.
Hydrogen generated by gut bacterial fermentation of lactulose selectively scavenges reactive oxygen species and upregulates Nrf2 expression in brain tissue, thereby suppressing oxidative stress markers and caspase-3-mediated apoptosis following cerebral ischemia-reperfusion.
Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).
See also:
https://h2-papers.org/en/papers/23954468