Abstract 229: Hydrogen sulfide donor, the Organic Polysulfide Diallyl Trisulfide Augments Ischemia-induced Angiogenesis by Upregulation of VEGF-Akt-eNOS Pathway

Introduction: Hydrogen sulfide (H2S) upregulates anti-oxidant, anti-apoptosis, anti-inflammatory, and cell survival. H2S plays an extremely important role in the homeostasis of the cardiovascular system and in the pathogenesis of cardiovascular disease. The diallyl trisulfide (DATS) is a polysulfide constituent found in garlic oil, and known as H2S donor that is able to release H2S continuously. Peripheral artery disease (PAD) causes considerable morbidity and mortality. The aim of this study was investigate whether the DATS would augment ischemia-induced angiogenesis. Methods: The unilateral permanent femoral artery ligation was performed in C57BL/6J mice (8-10 weeks old, n=8-10/group) and eNOS KO mice (8-10 weeks old, n=5-8/group), and vehicle or DATS (500 μg/kg/day) was injected intra-peritonealy up to 1 week following the hind limb ischemia (HLI). We evaluated the blood flow recovery using the laser Doppler perfusion image and capillary density stained with CD31 at 3 weeks following HLI. We assessed VEGF level by qPCR analysis and activations of eNOS and Akt by western blot analysis in ischemic tissues. Moreover, we cultured HUVECs in a hypoxic chamber with serum starvation for 24 hour, and then evaluated apoptosis by tunnel staining and oxidative stress by DHE staining with or without DATS (50 μmol). We also evaluated activations of eNOS and Akt in cultured HUVECs with or without DATS. Results: DATS treatment significantly increased blood flow (0.45 vs 0.78,p<0.05) and capillary density (1.57 vs 1.85,p<0.05) at 3 weeks following HLI compared to vehicle. DATS also increased mRNA level of VEGF and activation of Akt and eNOS at 3 days following HLI. On the other hand, DATS treatment failed to increase blood flow and capillary density at 3 weeks following HLI in eNOS KO mice. The DATS treatment inhibited apoptosis and oxidative stress in cultured HUVECs via activation of Akt and eNOS pathway in vitro. Conclusions: Our results indicate that DATS treatment could augment ischemia-induced angiogenesis by upregulation of VEGF-Akt-eNOS pathway that leads to inhibitions of apoptosis and oxidative stress. These results suggest that administration of H2S releasing agents might be efficacious for the treatment of PAD.

Download Full-text

Diallyl Trisulfide Suppresses Oxidative Stress-Induced Activation of Hepatic Stellate Cells through Production of Hydrogen Sulfide

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/1406726 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 13

Author(s):

Feng Zhang ◽

Huanhuan Jin ◽

Li Wu ◽

Jiangjuan Shao ◽

Xiaojing Zhu ◽

...

Keyword(s):

Oxidative Stress ◽

Hydrogen Sulfide ◽

Hepatic Stellate Cells ◽

Lipid Peroxide ◽

Stellate Cells ◽

Cyclin B1 ◽

Diallyl Trisulfide ◽

Fibrotic Liver ◽

Production Of Hydrogen ◽

And Oxidative Stress

Accumulating data reveal that garlic has beneficial effects against chronic liver disease. We previously reported that diallyl trisulfide (DATS), the primary organosulfur compound in garlic, reduced fibrosis and attenuated oxidative stress in rat fibrotic liver. The present study was aimed at elucidating the underlying mechanisms. The primary rat hepatic stellate cells (HSCs) were cultured and stimulated with hydrogen peroxide (H2O2) for inducing HSC activation under oxidative stress. We examined the effects of DATS on the profibrogenic properties and oxidative stress in H2O2-treated HSCs. The results showed that DATS suppressed and reduced fibrotic marker expression in HSCs. DATS arrested cell cycle at G2/M checkpoint associated with downregulating cyclin B1 and cyclin-dependent kinase 1, induced caspase-dependent apoptosis, and reduced migration in HSCs. Moreover, intracellular levels of reactive oxygen species and lipid peroxide were decreased by DATS, but intracellular levels of glutathione were increased in HSCs. Furthermore, DATS significantly elevated hydrogen sulfide (H2S) levels within HSCs, but iodoacetamide (IAM) reduced H2S levels and significantly abrogated DATS production of H2S within HSCs. IAM also abolished all the inhibitory effects of DATS on the profibrogenic properties and oxidative stress in HSCs. Altogether, we demonstrated an H2S-associated mechanism underlying DATS inhibition of profibrogenic properties and alleviation of oxidative stress in HSCs. Modulation of H2S production may represent a therapeutic remedy for liver fibrosis.

Download Full-text

The hydrogen sulfide releasing compounds ATB-346 and diallyl trisulfide attenuate streptozotocin-induced cognitive impairment, neuroinflammation, and oxidative stress in rats: involvement of asymmetric dimethylarginine

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2015-0316 ◽

2016 ◽

Vol 94 (7) ◽

pp. 699-708 ◽

Cited By ~ 15

Author(s):

Dalia K. Mostafa ◽

Nesrine M. El Azhary ◽

Rasha A. Nasra

Keyword(s):

Oxidative Stress ◽

Hydrogen Sulfide ◽

Cognitive Impairment ◽

Asymmetric Dimethylarginine ◽

Therapeutic Potential ◽

Memory Function ◽

Diallyl Trisulfide ◽

Beneficial Effects ◽

Behavioural Performance ◽

And Oxidative Stress

Hydrogen sulfide (H2S) has attracted interest as a gaseous mediator involved in diverse processes in the nervous system, particularly with respect to learning and memory. However, its therapeutic potential in Alzheimer disease (AD) is not fully explored. Therefore, the effects of H2S-releasing compounds against AD-like behavioural and biochemical abnormalities were investigated. Memory deficit was induced by intracerberoventicular injection of streptozotocin (STZ, 3 mg·kg−1). Animals were randomly assigned into 5 groups (12 rats each): normal control, STZ treated, and 3 drug-treated groups receiving naproxen, H2S-releasing naproxen (ATB-346), and diallyl trisulfide in 20, 32, 40 mg·kg−1·day−1, respectively. Memory function was assessed by passive avoidance and T-maze tasks. After 21 days, hippocampal IL-6, malondialdehyde, reduced glutathione (GSH), asymmetric dimethylarginine (ADMA), and acetylcholinestrase activity were determined. ATB-346 and diallyl trisulfide ameliorated behavioural performance and reduced malondialdehyde, ADMA, and acetylcholinestrase activity while increasing GSH. This study demonstrates the beneficial effects of H2S release in STZ-induced memory impairment by modulation of neuroinflammation, oxidative stress, and cholinergic function. It also delineates the implication of ADMA to the cognitive impairment induced by STZ. These findings draw the attention to H2S-releasing compounds as new candidates for treating neurodegenerative disorders that have prominent oxidative and inflammatory components such as AD.

Download Full-text

Endothelial deletion of PKCδ prevents VEGF inhibition and restores blood flow reperfusion in diabetic ischemic limb

Diabetes and Vascular Disease Research ◽

10.1177/1479164121999033 ◽

2021 ◽

Vol 18 (2) ◽

pp. 147916412199903

Author(s):

Laura Croteau ◽

Clément Mercier ◽

Étienne Fafard-Couture ◽

Alexandre Nadeau ◽

Stéphanie Robillard ◽

...

Keyword(s):

Blood Flow ◽

Phosphatase Activity ◽

Capillary Density ◽

Artery Ligation ◽

Vegf Signaling ◽

Post Surgery ◽

Src Homology ◽

Artery Disease ◽

Ischemic Muscle

Aims: Peripheral artery disease is a complication of diabetes leading to critical hindlimb ischemia. Diabetes-induced inhibition of VEGF actions is associated with the activation of protein kinase Cδ (PKCδ). We aim to specifically investigate the role of PKCδ in endothelial cell (EC) function and VEGF signaling. Methods: Nondiabetic and diabetic mice, with ( ec-Prkcd−/−) or without ( ec-Prkcdf/f) endothelial deletion of PKCδ, underwent femoral artery ligation. Blood flow reperfusion was assessed up to 4 weeks post-surgery. Capillary density, EC apoptosis and VEGF signaling were evaluated in the ischemic muscle. Src homology region 2 domain-containing phosphatase-1 (SHP-1) phosphatase activity was assessed in vitro using primary ECs. Results: Ischemic muscle of diabetic ec-Prkcdf/f mice exhibited reduced blood flow reperfusion and capillary density while apoptosis increased as compared to nondiabetic ec-Prkcdf/f mice. In contrast, blood flow reperfusion and capillary density were significantly improved in diabetic ec-Prkcd−/− mice. VEGF signaling pathway was restored in diabetic ec-Prkcd−/− mice. The deletion of PKCδ in ECs prevented diabetes-induced VEGF unresponsiveness through a reduction of SHP-1 phosphatase activity. Conclusions: Our data provide new highlights in mechanisms by which PKCδ activation in EC contributed to poor collateral vessel formation, thus, offering novel therapeutic targets to improve angiogenesis in the diabetic limb.

Download Full-text

ACS67, a Hydrogen Sulfide–Releasing Derivative of Latanoprost Acid, Attenuates Retinal Ischemia and Oxidative Stress to RGC-5 Cells in Culture

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.09-3999 ◽

2010 ◽

Vol 51 (1) ◽

pp. 284 ◽

Cited By ~ 44

Author(s):

Neville N. Osborne ◽

Dan Ji ◽

Aman S. Abdul Majid ◽

Rebecca J. Fawcett ◽

Anna Sparatore ◽

...

Keyword(s):

Oxidative Stress ◽

Hydrogen Sulfide ◽

Retinal Ischemia ◽

Cells In Culture ◽

And Oxidative Stress

Download Full-text

NaHS inhibits NF-κB signal against inflammation and oxidative stress in post-infectious irritable bowel syndrome

RSC Advances ◽

10.1039/c6ra13849g ◽

2016 ◽

Vol 6 (69) ◽

pp. 64208-64214 ◽

Cited By ~ 2

Author(s):

Shenglan Yang ◽

Danfang Deng ◽

Yingying Luo ◽

Yanran Wu ◽

Rui Zhu ◽

...

Keyword(s):

Oxidative Stress ◽

Irritable Bowel Syndrome ◽

Hydrogen Sulfide ◽

Murine Model ◽

Irritable Bowel ◽

And Oxidative Stress ◽

Post Infectious

In this study, the alleviating role of hydrogen sulfide (H2S) was investigated in a Post-Infectious Irritable Bowel Syndrome (PI-IBS) murine model and Caco-2 cells.

Download Full-text

Effects of SLIRP on Sperm Motility and Oxidative Stress

BioMed Research International ◽

10.1155/2020/9060356 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5

Author(s):

Dan Shan ◽

Samuel Kofi Arhin ◽

Junzhao Zhao ◽

Haitao Xi ◽

Fan Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Protein Expression ◽

Manganese Superoxide Dismutase ◽

Mrna Level ◽

Atp Content ◽

Human Male ◽

Manganese Superoxide ◽

Polymerase Chain ◽

And Oxidative Stress ◽

Relative Mrna Expression

Background. Deficient spermatozoon motility is one of the main causes of male infertility. However, there are still no accurate and effective treatments in a clinical setting for male asthenospermia. Exploring the genes and mechanism of asthenospermia has become one of the hot topics in reproductive medicine. Our aim is to study the effect of SLRIP on human spermatozoon motility and oxidative stress. Methods. Sperm samples were collected including a normospermia group (60 cases) and an asthenospermia group (50 cases). SLIRP protein expression in spermatozoa was examined by western blotting, and relative mRNA expression of SLIRP in spermatozoa was quantified by reverse transcription polymerase chain reaction. Levels of reactive oxygen species (ROS), adenosine triphosphate (ATP) content, and the activity of manganese superoxide dismutase (MnSOD) in spermatozoa were also measured. Results. The mRNA level and protein expression of SLIRP in the asthenospermia group were significantly reduced compared with those in the normospermia group. The ROS active oxygen level in the asthenospermia group significantly increased; however, the ATP content decreased significantly as well as the activity of MnSOD. Conclusion. SLIRP regulates human male fertility, and SLIRP and sperm progressive motility are positively correlated. The expression of SLIRP is declined, oxidative damage is increased, and energy metabolism is decreased in spermatozoa of asthenospermia patients compared to normospermia participants.

Download Full-text