Ameliorative effects of hydrogen sulfide (NaHS) on chronic kidney disease-induced brain dysfunction in rats: implication on role of nitric oxide (NO) signaling
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Chronic kidney disease (CKD) is a major public health problem worldwide and is associated with spatial learning deficits. The aim of the present study was to evaluate the protective effects of hydrogen sulfide (H2S) on CKD-mediated behavioral deficits with emphasis to the role of nitric oxide (NO) in these effects. Fifty rats were randomly allocated to five experimental groups including: sham, Five-sixth (5/6) nephrectomy (Nx), 5/6Nx + NaHS, 5/6Nx + NaHS+L-nitroarginine methyl ester (L-NAME), and 5/6Nx + NaHS+aminoguanidine (AMG). Twelve weeks after 5/6Nx, we evaluated proteinuria, creatinine clearance (CrCl), oxidative/antioxidant status, and hippocampus neuro-inflammation and NO synthase genes in all groups. Furthermore, training trials of all animals were conducted in the Morris water maze (MWM) task one day before animal euthanizing. As predicted, 5/6Nx induced several injuries, including enhancement of proteinuria and reduction of CCr, oxidant/antioxidant imbalance and up-regulation of TNF-α and IL-1β gene expressions in the hippocampus tissues. As predicted, 5/6Nx resulted in learning and memory impairments, and increased escape latency during acquisition trials in the MWM task. Interestingly, NaHS (H2S donor) improved behavioral deficits, renal dysfunction, accelerated anti-oxidant/anti-inflammatory responses and increased eNOS and decreased iNOS. Moreover, these effects of NaHS were prevented by L-NAME but not AMG co-administration. In conclusion, H2S ameliorates CKD-mediated brain dysfunctions, through interaction with NO signaling in the hippocampus.
KeywordsChronic kidney disease Hydrogen sulfide Oxidative stress Inflammation Cognitive dysfunction Nitric oxide
Askari H. and Sanadgol N. contributed to the conception, study design and manuscript preparation. Nouri M., Mirfallah R., Tahmasbi N., Abedi M. and Salarian A. did the data collection. Fatima and MF. Abazari contributed to the critical revision of the article. Askari H. and Belaran M. did the analysis and interpretation of data. Ghoraeian P. and Torabinejad S. assisted on western blot analysis.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This study partially supported by University of Zabol (grant code: UOZ-GR-9517-13).
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