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Hydrogen sulfide attenuates homocysteine induced neurovascular dysfunction
Author(s) -
Kamat Pradip,
Kalani Anuradha,
Givvimani Srikanth,
Tyagi Suresh C,
Tyagi Neetu
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb728
Subject(s) - cystathionine beta synthase , homocysteine , neurovascular bundle , oxidative stress , hyperhomocysteinemia , cystathionine gamma lyase , chemistry , endothelial dysfunction , nitric oxide , pharmacology , endocrinology , nitric oxide synthase , medicine , biochemistry , pathology , enzyme , cysteine
High levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), are associated with neurovascular diseases such as vascular dementia. Endogenously, hydrogen sulfide (H 2 S) is produced as a metabolite of Hcy by cystathionine β‐synthase, cystathionine γ‐lyase, and 3‐mercaptopyruvate sulfurtransferase. H 2 S is a potent anti‐oxidant, anti‐inflammatory, anti‐hypertensive and vasorelaxing agent. However, the effect of H 2 S has not been explored in Hcy induced neurovascular dysfunction. Therefore, the present study was designed to explore the protective role of H 2 S in neurovascular dysfunction induced by Hcy. To test this hypothesis we employed 8 weeks old male wild type (WT), WT+aCSF WT+ Hcy (5μmol in aCSF) intra‐cerebral injection (one time only prior to NaHS treatment), WT+Hcy +NaHS (sodium hydrogen sulfide, precursor of H 2 S, 30 μmol/L in 0.9% normal saline). NaHS was injected intra‐peritoneally once daily for a period of 7 days after Hcy treatment. Memory function was assessed by novel object recognition test. The brain tissues were analyzed for neuronal loss, oxidative‐nitrosative stress, matrix metalloproteinases, tight junction proteins, tissue inhibitor of matrix metalloproteinases, cell death, neuroinflammatory and synaptic markers by Western Blot, qRT‐PCR and IHC. Hcy administration induced oxidative‐nitrosative stress, apoptosis, neuronal loss, neuro‐inflammation along with vascular dysfunction. Interestingly, administration of NaHS significantly improved neurovascular dysfunction in Hcy treated groups thereby suggesting its potential therapeutic role against HHcy‐related neurovascular diseases.