Lactulose ameliorates cerebral ischemia-reperfusion injury in rats by inducing hydrogen by activating Nrf2 expression
by Zhimin Kang, Xue-Jun Sun, Wenwu Liu, Xiao Chen, Xiao Zhai, Zhouheng Ye, Qijin Wang, Jiazi Shi, Duo Shi, Hongda Bi, Ming Li
Abstract:
Molecular hydrogen has been proved effective in ameliorating cerebral ischemia/reperfusion (I/R) injury by selectively neutralizing reactive oxygen species. Lactulose can produce considerable amount of hydrogen through fermentation by the bacteria in the gastrointestinal tract. To determine the neuroprotective effects of lactulose against cerebral I/R injury in rats and explore the probable mechanisms, we carried out this study. The stroke model was produced on Sprague-Dawley(SD) rats through middle cerebral artery occlusion(MCAO). Intragastric administration of lactulose substantially increased hydrogen breath concentration. Behavioral and histopathological verifications matched biochemical findings. Behaviorally, rats in lactulose administration group won higher neurological scores and showed shorter escape latency time in Morris test. Morphologically, 2,3,5-triphenyltetrazolium chloride (TTC) showed smaller infarction volume; Nissl staining manifested relatively clear and intact neurons and TUNEL staining showed less apoptotic neurons. Biochemically, lactulose decreased brain malondialdehyde(MDA) content, caspase-3 activity, 3-nitrotyrosine(3-NT) and 8-hydroxy-2-deoxyguanosine(8-OHdG) concentration and increased superoxide dismutase(SOD) activity. And the effects of lactulose were superior to edaravone. Lactulose orally administered activated the expression of NF-E2-related factor 2(Nrf2) in the brain verified by RT-PCR and Western blot. The antibiotics suppressed the neuroprotective effects of lactulose via reducing hydrogen production. Our study for the first time demonstrated a novel therapeutic effect of lactulose on cerebral ischemia/reperfusion injury and the probable underlying mechanisms. Lactulose intragastrically administered possessed neuroprotective effects on cerebral I/R injury in rats, which could be attributed to hydrogen production by the fermentation of lactulose through intestinal bacteria and Nrf2 activation.
Read more:
https://doi.org/10.1016/j.freeradbiomed.2013.08.004
Related Articles:
Background: Inhaled molecular hydrogen gas (H2) has been shown to improve outcomes in animal models of cardiac arrest (CA). H2 inhalation is safe and feasible in patients after CA. We investigated whether inhaled H2 would improve outcomes after out-of-hospital CA…
Background: We have previously reported the efficacy of post-reperfusion H2 gas treatment in cold storage (CS) and subsequent reperfusion of the rat liver. The present study aimed to evaluate the effect of H2 gas treatment during hypothermic machine perfusion (HMP)…
We previously reported the efficacy of cold storage (CS) using a heavy water-containing solution (Dsol) and post-reperfusion hydrogen gas treatment separately. This study aimed to clarify the combined effects of these treatments. Rat livers were subjected to 48-hour CS and…
Cerebral ischemia/reperfusion (CI/R) injury causes high disability and mortality. Hydrogen (H2) enhances tolerance to an announced ischemic event; however, the therapeutic targets for the effective treatment of CI/R injury remain uncertain. Long non-coding RNA lincRNA-erythroid prosurvival (EPS) (lincRNA-EPS) regulate various…
Background: This study sought to investigate therapeutic effects of hydrogen-rich saline (HRS) combined with hyperbaric oxygen (HBO2) in an experimental rat model of acute lung injury (ALI). Method: Forty male Sprague-Dawley rats were randomly divided into sham, LPS, LPS +…
Cardiac surgery-associated acute kidney injury (CS-AKI) is a common postoperative complication, mostly due increasing oxidative stress. Recently, molecular hydrogen (H2 gas), has also been applied to cardiac surgery due to its ability to reduce oxidative stress. We evaluated the potential…
0 Comments