Nitric oxide : biology and chemistry
-
Acute tissue damage is accompanied by synthesis of nitric oxide (NO) in the inflamed tissue as well as in the spinal cord. NO release at the spinal level is likely involved in the neuroplastic changes contributing to pain. Also, previous studies indicate that this could be due to the inducible isoform of the nitric oxide synthase (iNOS) enzyme. ⋯ Also, spinal NO level decreased after i.t. drug administration. Post-incision drug treatment resulted in greater antinociceptive effect at day 1 though not on day 2. These results indicate involvement of NO in postincisional nociception in rats.
-
Mitochondria-targeted hydrogen sulfide donor AP39, [(10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol-5yl)phenoxy)decyl) triphenylphosphonium bromide], exhibits cytoprotective effects against oxidative stress in vitro. We examined whether or not AP39 improves the neurological function and long term survival in mice subjected to cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). ⋯ The current results suggest that administration of mitochondria-targeted sulfide donor AP39 at the time of CPR or after ROSC improves the neurological function and long term survival rates after CA/CPR by maintaining mitochondrial integrity and reducing oxidative stress.
-
Increasing evidence suggests that the pathogenesis of neuropathic pain is mediated through activation of microglia in the spinal cord. Hydrogen sulfide attenuates microglial activation and central nervous system inflammation; however, the role of hydrogen sulfide in neuropathic pain is unclear. In this study, we examined the effects of hydrogen sulfide breathing on neuropathic pain in mice. ⋯ Inhaled hydrogen sulfide prevented the neuropathic pain behavior and attenuated the upregulation of inflammatory cytokines. Sodium sulfide inhibited IL-6-induced activation of primary microglia. These results suggest that inhaled hydrogen sulfide prevents the development of neuropathic pain in mice possibly via inhibition of the activation of microglia in the spinal cord.
-
Oxidative stress plays a role in maintaining high arterial blood pressure and contributes to the vascular changes that lead to hypertension. Consumption of polyphenol-rich foods has demonstrated their beneficial role in the prevention and treatment of hypertension. Curcumin (CUR), a phenolic compound present in the rhizomes of turmeric, possesses cardiovascular protective, anti-inflammatory and antioxidant properties. ⋯ CUR also attenuated hypertension-induced oxidative stress and vascular structural modifications. These effects were associated with elevated plasma nitrate/nitrite, upregulated eNOS expression, downregulated p47phox NADPH oxidase and decreased superoxide production in the vascular tissues. The overall findings of this study suggest the mechanisms responsible for the antihypertensive action of CUR in 2K-1C hypertension-induced endothelial dysfunction and vascular remodeling involve the improvement NO bioavailability and a reduction in oxidative stress.
-
The purpose of the current study was to investigate the effect of the recently synthesized mitochondrially-targeted H2S donor, AP39 [(10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol-5yl)phenoxy)decyl) triphenylphosphonium bromide], on bioenergetics, viability, and mitochondrial DNA integrity in bEnd.3 murine microvascular endothelial cells in vitro, under normal conditions, and during oxidative stress. Intracellular H2S was assessed by the fluorescent dye 7-azido-4-methylcoumarin. For the measurement of bioenergetic function, the XF24 Extracellular Flux Analyzer was used. ⋯ AP39 pretreatment attenuated these responses. Glucose oxidase induced a preferential damage to the mitochondrial DNA; AP39 (100 nM) pretreatment protected against it. In conclusion, the current paper documents antioxidant and cytoprotective effects of AP39 under oxidative stress conditions, including a protection against oxidative mitochondrial DNA damage.