scholarly journals 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

2016 ◽  
Vol 94 (7) ◽  
pp. 699-708 ◽  
Author(s):  
Dalia K. Mostafa ◽  
Nesrine M. El Azhary ◽  
Rasha A. Nasra

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.

2021 ◽  
Vol 3 (2) ◽  
pp. 30-32
Author(s):  
Hiroshi Bando

Various discussion exists concerning ketone bodies (KB) for beneficial effects. In 2021, the American College of Cardiology (ACC) has presented the therapeutic potential of KB for cardiovascular (CV) disease. KB cover 10-15% of cardiac production of ATP, elevation of cardiac energetics, and reduction of cardiac remodeling, inflammation, and oxidative stress.


2020 ◽  
Vol 42 ◽  
pp. e50588
Author(s):  
Stephanie Carvalho Borges ◽  
Lia Mara Teobaldo Tironi ◽  
Luísa Mota da Silva ◽  
Nilza Cristina Buttow

 In addition to several local pathophysiological consequences, intestinal injury that is caused by ischemia and reperfusion can result in the development of lesions in remote organs. Curcumin has therapeutic potential because of its antiinflammatory and antioxidant effects. The present study evaluated the effects of curcumin on oxidative and inflammatory parameters in the liver and kidneys in rats that were subjected to intestinal ischemia and reperfusion. The rats were subjected to 45 min. of ischemia followed by 7 days of reperfusion and treated daily with 60 mg kg-1 curcumin. The liver and kidneys were collected, weighed, and biochemically analyzed. Intestinal ischemia and reperfusion increased levels of lipid hydroperoxide (LOOH), decreased levels of reduced glutathione (GSH), and increased the enzymatic activity of superoxide dismutase (SOD), glutathione S-transferase (GST), and myeloperoxidase (MPO) in the liver. Intestinal ischemia and reperfusion decreased kidney weight and increased GST activity in the kidneys. Curcumin prevented these changes in the liver and kidneys. Intestinal ischemia and reperfusion mainly affected the liver, promoting inflammation and oxidative stress. The kidneys underwent repair much earlier than the liver, in which they did not present alterations of MPO or main parameters of oxidative stress after 7 days of reperfusion. Treatment with curcumin had beneficial effects, ameliorating or even preventing injury that was caused by intestinal ischemia and reperfusion in the liver and kidneys in rats


2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Feng Zhang ◽  
Huanhuan Jin ◽  
Li Wu ◽  
Jiangjuan Shao ◽  
Xiaojing Zhu ◽  
...  

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.


2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Ryo Hayashida ◽  
Kazuhisa Kondo ◽  
Satoshi Shintani ◽  
Toyoaki Murohara

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.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1311
Author(s):  
Shu-Ju Wu ◽  
Chian-Jiun Liou ◽  
Ya-Ling Chen ◽  
Shu-Chen Cheng ◽  
Wen-Chung Huang

Fucoxanthin is isolated from brown algae and was previously reported to have multiple pharmacological effects, including anti-tumor and anti-obesity effects in mice. Fucoxanthin also decreases the levels of inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. The purpose of the present study was to investigate the effects of fucoxanthin on the oxidative and inflammatory responses in inflammatory human tracheal epithelial BEAS-2B cells and attenuated airway hyperresponsiveness (AHR), airway inflammation, and oxidative stress in asthmatic mice. Fucoxanthin significantly decreased monocyte cell adherence to BEAS-2B cells. In addition, fucoxanthin inhibited the production of pro-inflammatory cytokines, eotaxin, and reactive oxygen species in BEAS-2B cells. Ovalbumin (OVA)-sensitized mice were treated by intraperitoneal injections of fucoxanthin (10 mg/kg or 30 mg/kg), which significantly alleviated AHR, goblet cell hyperplasia and eosinophil infiltration in the lungs, and decreased Th2 cytokine production in the BALF. Furthermore, fucoxanthin significantly increased glutathione and superoxide dismutase levels and reduced malondialdehyde (MDA) levels in the lungs of asthmatic mice. These data demonstrate that fucoxanthin attenuates inflammation and oxidative stress in inflammatory tracheal epithelial cells and improves the pathological changes related to asthma in mice. Thus, fucoxanthin has therapeutic potential for improving asthma.


Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4210
Author(s):  
Yan Zhou ◽  
Chunxiu Zhou ◽  
Xutao Zhang ◽  
Chi Teng Vong ◽  
Yitao Wang ◽  
...  

Coptisine is the major bioactive protoberberine alkaloid found in Rhizoma Coptidis. Coptisine reduces inflammatory responses and improves glucose tolerance; nevertheless, whether coptisine has vasoprotective effect in diabetes is not fully characterized. Conduit arteries including aortas and carotid arteries were obtained from male C57BL/6J mice for ex vivo treatment with risk factors (high glucose or tunicamycin) and coptisine. Some arterial rings were obtained from diabetic mice, which were induced by high-fat diet (45% kcal% fat) feeding for 6 weeks combined with a low-dose intraperitoneal injection of streptozotocin (120 mg/kg). Functional studies showed that coptisine protected endothelium-dependent relaxation in aortas against risk factors and from diabetic mice. Coptisine increased phosphorylations of AMPK and eNOS and downregulated the endoplasmic reticulum (ER) stress markers as determined by Western blotting. Coptisine elevates NO bioavailability and decreases reactive oxygen species level. The results indicate that coptisine improves vascular function in diabetes through suppression of ER stress and oxidative stress, implying the therapeutic potential of coptisine to treat diabetic vasculopathy.


Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 507
Author(s):  
Rosaria Meccariello ◽  
Stefania D’Angelo

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3442
Author(s):  
Yaowared Chulikhit ◽  
Wichitsak Sukhano ◽  
Supawadee Daodee ◽  
Waraporn Putalun ◽  
Rakvajee Wongpradit ◽  
...  

The effects of the phytoestrogen-enriched plant Pueraria mirifica (PM) extract on ovari-ectomy (OVX)-induced cognitive impairment and hippocampal oxidative stress in mice were investigated. Daily treatment with PM and 17β-estradiol (E2) significantly elevated cognitive behavior as evaluated by using the Y maze test, the novel object recognition test (NORT), and the Morris water maze test (MWM), attenuated atrophic changes in the uterus and decreased serum 17β-estradiol levels. The treatments significantly ameliorated ovariectomy-induced oxidative stress in the hippocampus and serum by a decrease in malondialdehyde (MDA), an enhancement of superoxide dismutase, and catalase activity, including significantly down-regulated expression of IL-1β, IL-6 and TNF-α proinflammatory cytokines, while up-regulating expression of PI3K. The present results suggest that PM extract suppresses oxidative brain damage and dysfunctions in the hippocampal antioxidant system, including the neuroinflammatory system in OVX animals, thereby preventing OVX-induced cognitive impairment. The present results indicate that PM exerts beneficial effects on cognitive deficits for which menopause/ovariectomy have been implicated as risk factors.


2010 ◽  
Vol 51 (1) ◽  
pp. 284 ◽  
Author(s):  
Neville N. Osborne ◽  
Dan Ji ◽  
Aman S. Abdul Majid ◽  
Rebecca J. Fawcett ◽  
Anna Sparatore ◽  
...  

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