Hydrogen Sulphide Ameliorates Dopamine-Induced Astrocytic Inflammation And Neurodegeneration In Minimal Hepatic Encephalopathy

It has been demonstrated that the action of dopamine (DA) could enhance the production of tumour necrosis factor-alpha (TNF-alpha) by astrocytes and potentiate neuronal apoptosis in minimal hepatic encephalopathy (MHE). Recently, sodium hydrosulfide (NaHS) has been found to have neuroprotective properties. Our study addressed whether NaHS could rescue DA-challenged inflammation and apoptosis in neurons to ameliorate memory impairment in MHE rats and in the neuron and astrocyte coculture system. We found that NaHS suppressed DA-induced p65 acetylation, resulting in reduced TNF-alpha production in astrocytes both in vitro and in vivo. Furthermore, decreased apoptosis was observed in neurons exposed to conditioned medium from DA + NaHS-challenged astrocytes, which was similar to the results obtained in the neurons exposed to TNF-alpha + NaHS, suggesting a therapeutic effect of NaHS on the suppression of neuronal apoptosis via the reduction of TNF-alpha level. DA triggered the inactivation of p70 S6 ribosomal kinase (S6K1) and dephosphorylation of Bad, resulting in the disaggregation of Bclxl and Bak and the release of cytochrome c (Cyt. c), and this process could be reversed by NaHS administration. Our work demonstrated that NaHS attenuated DA-induced astrocytic TNF-alpha release and ameliorated inflammation-induced neuronal apoptosis in MHE. Further research into this approach may uncover future potential therapeutic strategies for MHE.