Involvement of adenosine triphosphate-sensitive potassium channels in the neuroprotective activity of hydrogen sulfide in the 6-hydroxydopamine-induced animal model of Parkinson’s disease

Abstract

Studies have shown that hydrogen sulfide (H2S) exerts a neuroprotective effect and may have a therapeutic value for treating neurodegenerative diseases including Parkinson's disease. However, little is known about the mechanisms underlying the neuroprotective activity of H2S in vivo. Here, we evaluated the effect of glibenclamide, an ATP-sensitive potassium channel blocker, on the neuroprotective activity of H2S in the 6-hydroxydopamine (6-OHDA) animal model of Parkinson's disease. 6-OHDA was administered by stereotaxic surgery into the medial forebrain bundle. Sodium hydrosulfate (NaHS, 3 and 5.6 mg/kg), as a donor of H2S, alone or in combination with glibenclamide (5 mg/kg), was daily injected for 7 days starting 1-2 h before the stereotaxic surgery. After an apomorphine-induced rotational test, the number of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta was determined by immunofluorescence. The striatal dopamine level and oxidative stress markers were also measured in brain homogenates. Pretreatment with NaHS significantly attenuated 6-OHDA-induced motor asymmetry in the rotational test. Histological and biochemical evaluations demonstrated that NaHS, especially at high dose, increased the survival of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta and reduced the decreasing effect of 6-OHDA on striatal dopamine levels. However, co-administration of glibenclamide reversed the antiparkinsonian and neuroprotective effects of NaHS. However, glibenclamide did not change the reducing effect of NaHS on 6-OHDA-induced overproduction of malondialdehyde. Our data show that ATP-sensitive potassium channels are involved in the antiparkinsonian and neuroprotective effects of H2S in the 6-OHDA animal model of Parkinson's disease.

Extracellular Signal-Regulated Kinase 1/2 Pathway Is Insufficiently Involved in the Neuroprotective Effect by Hydrogen Sulfide Supplement in Experimental Glaucoma

“…17 Thus there exists a strong demand for exploration of neuroprotective strategies independent of IOP lowering to ameliorate glaucomatous neuropathy, and in this respect, H 2 S apparently tends to perform effectively, considering significant findings in the treatment of other neurodegenerative diseases in the central nervous system. [18][19][20] In line with expectations, H 2 S has shown profound involvement in various retinal neuropathy processes, while exogenous donors exhibited therapeutic potential in conditions of several retinal diseases. It has been confirmed that CBS, CSE, and 3-MST all existed in mammalian retina and positively correlated with the endogenous H 2 S level in retina under different pathological situations.…”

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

“…Sarookhani et al (2018) administered 4 µL (4 µg/µL) of 6-OHDA unilaterally into two sites and examined the sodium hydrosulfate (5.6 mg/kg) activity in male Wistar rat models. They used apomorphine (0.5 mg/kg, intraperitoneally) before the behavioral tests and found the motor defects contralateral rotations in all 6-OHDA-induced groups, revealed that pretreatment with sodium hydrosulfate did not protect 6-OHDA-induced PD impairments [ 97 ]. Romero-Sánchez et al (2020) administered 6, 10, and 16 µg of 6-OHDA in 2 µL (at 0.1 µL/min) unilaterally into left substantia nigra to induce the lesion and revealed that the impaired nigrostriatal dopaminergic pathway in male Wistar rat models.…”

NaSH increases SIRT1 activity and autophagy flux through sulfhydration to protect SH-SY5Y cells induced by MPP~+

“…NaHS reduced the apoptosis rate and the accumulation of cytotoxic substances MDA and 4-HNE, while increased the autophagy flux and expression of LC3 II/I and Beclin1 in SH-SY5Y cells induced by MPP~+. Exogenous application of H 2 S protected the SH-SY5Y cells against 6-hydroxydopamine-induced or rotenone-induced cell apoptosis and death [24]. In addition, inhaled NaHS or H 2 S was presented to show neuroprotection in rodent models of PD induced by neurotoxins [10].…”