A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile

Abstract

Although epilepsy is one of the most common neurologic disorders, there is still a lack of effective therapeutic drugs for it. Recently, we synthesized a novel hydrogen sulfide (H2S) donor, which is found to reduce seizures in animal models effectively. But it remains to be determined for its mechanism. In the present study, we found that the novel H2S donor could reduce pilocarpine-induced seizures in mice. It alleviated the epileptic behavior, the hippocampal electroencephalography (EEG) activity of seizures, and the damage of hippocampal neurons in status epilepticus mice. In addition, the novel H2S donor could reduce microglial inflammatory response. It not only reduced the upregulation of pro-inflammatory markers [inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2)] in status epilepticus mice, but also increased the levels of microglial anti-inflammatory marker arginase-1 (Arg-1). In lipopolysaccharide-treated microglia BV2 cells, administration of the H2S donor also significantly reduced the lipopolysaccharide-induced upregulation of the expression of the pro-inflammatory markers and increased the expression of the anti-inflammatory markers. Thus, the novel H2S donor regulates microglial inflammatory profile in status epilepticus mice and in vitro. These results suggested that the novel H2S donor can reduce seizures and regulate microglial inflammatory profile, which may be a novel mechanism and potential therapeutic strategy of the H2S donor anti-seizures.

Role of sulfide anion in the development of chronic alcoholic hepatitis under the conditions of modulation of adenosine monophosphate kinase – a correlational study

“…37 The appearance of the relationship with similar direction and strength between H 2 S and arginase activity in the group of chronic alcoholic hepatitis is also related to the biological effects of alcohol, namely its ability to decrease arginase activity, while H 2 S can increase its activity. [38][39] The inversely proportional strong relationship between the concentrations of H 2 S and L-oxyproline under conditions of chronic alcoholic hepatitis can be explained by the origin of free L-oxyproline, which under conditions of excessive accumulation of alcohol is released from collagen fibers during oxidative stress, while H 2 S is a powerful antioxidant. 40 Stimulation of the activation of the AMPK cascade in the background of simulation of alcohol intoxication significantly enhances the effect of H 2 S on the nitric oxide system.…”

Hydrogen Sulphide-Based Therapeutics for Neurological Conditions: Perspectives and Challenges

“…This study demonstrated that SE + H 2 S group had a shorter duration of seizure compared to the SE group. Additionally, this group showed delayed onset of seizure, reduced damage to the hippocampus and reduced pro-inflammatory state in microglia compared to the SE control group [ 62 ].…”