RESUMO
Aims: This study aims at investigating possible means of reducing cyanide toxicity by blocking NMDA R1 via ketamine (an NMDA R1 antagonist). This is to provide a template for quick arrest of cyanide toxicity in neurons under oxygen deprived condition. Place and Duration of Study: Bingham University, Department of Anatomy, Karu, Nigeria. The duration of the study was100 minutes. Methodology: Freshly harvested cortical tissue blocks were perfused in accessory cerebrospinal fluid (ACSF) containing all the necessary salts and glucose. The cultures were treated with ACSF (Control), ACSF+KCN (potassium cyanide), ACSF+KCN+Ketamine and ACSF+Ketamine for a total duration of 100 minutes at 37ºC. Results: The Ketamine had a protective and reversal effects on the tissues both for oxygen deprivation and cyanide toxicity, The cells in tissues treated with ACSF+KCN+Ketamine showed normal appearance of cell body and axonal projections, the cells treated with ACSF+Ketamine showed fewer degenerating cells compared to those treated with cyanide. Conclusion: Ketamine, an NMDA R1 antagonist is neuroprotective against the toxicity of cyanide.
RESUMO
Mitochondrial mechanism of oxidative stress and matrix metalloproteinase (MMP) activation was unclear. Our recent data suggested that MMPs are localized to mitochondria and activated by peroxynitrite, which causes cardiovascular remodeling and failure. Recently, we have demonstrated that elevated levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy) increase oxidative stress in the mitochondria. Although HHcy causes heart failure, interestingly, it is becoming very clear that Hcy can generate hydrogen sulfide (H2S), if the enzymes cystathionine β-synthase (CBS) and cystathionine -lyase (CGL) are present. H2S is a strong anti-oxidant and vasorelaxing agent. Paradoxically, it is interesting that Hcy, a precursor of H2S can be cardioprotective. The CGL is ubiquitous, while the CBS is not present in the vascular tissues. Therefore, under normal condition, only half of Hcy can be converted to H2S. However, there is strong potential for gene therapy of CBS to vascular tissue that can mitigate the detrimental effects of Hcy by converting it to H2S. This scenario is possible, if the activities of both the enzymes (CBS and CGL) are increased in tissues by gene therapy.