Hydrogen sulfide protects against cognitive impairment induced by hepatic ischemia and reperfusion via attenuating neuroinflammation

Abstract

Previously, hepatic ischemia followed by reperfusion (hepatic I/R) has been found to cause cognitive impairment. Hydrogen sulfide (H 2 S) attenuates hepatectomy induced cognitive deficits and also protects against cognitive dysfunction induced by neurodegenerative diseases. In this study, we aim to determine whether sodium hydrosulfide (NaHS), a H 2 S donor, could alleviate hepatic I/R-induced cognitive impairment and the underlying mechanisms. Rats were injected intraperitoneally with NaHS (5 mg/kg/d) for 11 days. A segmental hepatic I/R model was established on the fourth day. Cognitive function, proinflammatory cytokines levels, and hippocampal ionized calcium-binding adaptor molecule 1 (Iba1) expression was analyzed. We found hepatic I/R increased proinflammatory cytokines levels in serum and hippocampus, up-regulated Iba1 expression, leading to cognitive impairment in rats. However, treatment with NaHS alleviated hepatic I/R induced these neuroinflammatory changes and effectively improved cognitive function. Thus, NaHS appears to protect against cognitive impairment in rats undergoing hepatic I/R by attenuating neuroinflammation in the hippocampus.

Hydrogen Sulfide Protects against Paraquat-Induced Acute Liver Injury in Rats by Regulating Oxidative Stress, Mitochondrial Function, and Inflammation

“…Compared with the control group, ROS levels were not significantly increased in rats treated with NaHS alone (Figures 3 and 2) and Nrf2 nuclear translocation or the increase in SOD, HO-1, and NQO-1 expression was not observed (Figures 2 and 5). These findings above are consistent with previous studies [34,35,38,39]. SIRT3 is a histone deacetylase localized predominantly in mitochondria and regulates mitochondrial enzymatic…”

“…PQ was intraperitoneally administered in rats at a dose of 20 mg/kg which was based on our previous study [10]. With reference to the previous studies [33][34][35], two different doses of NaHS as mentioned above were administered intraperitoneally one hour prior to exposure to PQ. At 12 h, 24 h, and 48 h after PQ administration, the rats (n = 6) were taken from each group and sacrificed after deep anesthesia at each time point.…”

Toxic effects of hydrogen sulfide donor NaHS induced liver apoptosis is regulated by complex IV subunits and reactive oxygen species generation in rats

“…There is evidence that NaHS, which releases H 2 S when in aqueous solution, is protective in a variety of animal models of disease . Tu et al have demonstrated that NaHS (5 mg/kg/day for 11 days, ip) protects against cognitive impairment induced by hepatic ischemia‐reperfusion via attenuating neuroinflammation . Du et al have demonstrated that NaHS (0.78, 1.56, and 3.12 mg/kg, ip) is positively correlated with the dosage provided a protective effect against acute lung injury in the LPS‐induced rat models .…”

Hydrogen sulfide attenuates chronic restrain stress-induced cognitive impairment by upreglulation of Sirt1 in hippocampus

“…H 2 S, a gaseous signaling molecule, scavenges ROS and protects neurons against oxygen stress damage, neurotoxicity, and cell apoptosis [ 33 , 34 ]. Furthermore, H 2 S plays an important role in regulation of learning and memory [ 10 ]. To investigate the beneficial effect of H 2 S on CRS-induced deficits in learning and memory, rats were cotreated with NaHS and CRS for 28 d, and the functions of learning and memory of rats were tested with Y-maze test, Novel object recognition test, and Morris water maze test.…”

“…Hydrogen sulfide (H 2 S), the third gasotransmitter along with nitric oxide (NO) and carbon monoxide (CO) [ 5 ], plays potent protective effects in the central nervous system [ 6 , 7 ]. Accumulating evidences demonstrate that H 2 S facilitates the induction of hippocampal long term potentiation (LTP) [ 8 , 9 ] and attenuates hepatic I/R- or β-amyloid-induced impairment in spatial learning and memory [ 10 - 13 ]. Moreover, our recent study certified that disturbance of endogenous H 2 S generation in hippocampus is involved in deficits in learning and memory [ 14 , 15 ] and that H 2 S antagonizes formalydehyde-exerted deficits in cognitive function [ 16 ].…”