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Synthesis and effects of pyrazolines and isoxazoles on the phagocytic chemotaxis and release of reactive oxygen species by zymosan stimulated human neutrophils

Bukhari SN, Jantan I, Wai LK, Lajis NH, Abbas F, Jasamai M

Med Chem, 2013 Dec;9(8):1091-8.
PMID: 23092331

A series of novel isoxazole and pyrazoline derivatives has been synthesized and evaluated for their effects on the chemiluminescence and chemotactic activity of human phagocytes. Their effects on the chemotactic migration of isolated polymorphonuclear leukocytes (PMNs) and on the release of reactive oxygen species (ROS) during respiratory burst of human whole blood and PMNs were carried out using the Boyden chamber technique and luminol-based chemiluminescence assay, respectively. Of the compounds tested, compounds 8, 9, 11 and 12 exhibited higher inhibitory activity on the release of ROS (with IC50 values ranging from 5.6 to 8.4 μM) than acetylsalicylic acid (IC50 = 9.5 μ M). These compounds also showed strong inhibitory activity on the migration of PMNs with compound 8 exhibiting an IC50 value lower than that of ibuprofen. The results suggest that some of these isoxazole and pyrazoline derivatives have ability to modulate the innate immune response of phagocytes at different steps, indicating their potential as a source of new immunomodulatory agents.

Matched MeSH terms: Reactive Oxygen Species/metabolism*
Influence of agitation speed on tannase production and morphology of Aspergillus niger FETL FT3 in submerged fermentation

Darah I, Sumathi G, Jain K, Lim SH

Appl Biochem Biotechnol, 2011 Dec;165(7-8):1682-90.
PMID: 21947762 DOI: 10.1007/s12010-011-9387-8

Agitation speed was found to influence the tannase production and fungal growth of Aspergillus niger FETL FT3. The optimal agitation speed was at 200 rpm which produced 1.41 U/ml tannase and 3.75 g/l of fungal growth. Lower or higher agitation speeds than 200 rpm produced lower enzyme production and fungal growth. Based on the SEM and TEM micrograph observation, there was a significant correlation between agitation speed and the morphology of the fungal mycelia. The results revealed an increase of the enzyme production with the change of the fungal growth morphology from filamentous to pelleted growth forms. However, the exposure to higher shear stress with an increasing agitation speed of the shaker also resulted in lower biomass yields as well as enzyme production.

Matched MeSH terms: Oxygen/metabolism
Neuroprotection of α-synuclein under acute and chronic rotenone and maneb treatment is abolished by its familial Parkinson's disease mutations A30P, A53T and E46K

Choong CJ, Say YH

Neurotoxicology, 2011 Dec;32(6):857-63.
PMID: 21658409 DOI: 10.1016/j.neuro.2011.05.012

α-Synuclein (α-Syn) plays a crucial role in the pathophysiology of Parkinson's disease (PD). α-Syn has been extensively studied in many neuronal cell-based PD models but has yielded mixed results. The objective of this study was to re-evaluate the dual cytotoxic/protective roles of α-Syn in dopaminergic SH-SY5Y cells. Stable SH-SY5Y cells overexpressing wild type or familial α-Syn mutants (A30P, E46K and A53T) were subjected to acute and chronic rotenone and maneb treatment. Compared with untransfected SH-SY5Y cells, wild type α-Syn attenuated rotenone and maneb-induced cell death along with an attenuation of toxin-induced mitochondrial membrane potential changes and Reactive Oxygen Species level, whereas the mutant α-Syn constructs exacerbated environmental toxins-induced cytotoxicity. After chronic treatment, wild type α-Syn but not the mutant variants was found to rescue cells from subsequent acute hydrogen peroxide insult. These results suggest that the fundamental property of wild type α-Syn may be protective, and such property may be lost by its familial PD mutations.

Matched MeSH terms: Reactive Oxygen Species/metabolism
A videoendoscopic evaluation of the upper airway in South East Asian adults with obstructive sleep apnea

Abdullah B, Rajet KA, Abd Hamid SS, Mohammad WM

Sleep Breath, 2011 Dec;15(4):747-54.
PMID: 20957444 DOI: 10.1007/s11325-010-0431-7

OBJECTIVES: We aimed to evaluate the severity of upper airway obstruction at the retropalatal and retroglossal regions in obstructive sleep apnea (OSA) patients.
METHODOLOGY: This is a descriptive cross-sectional study at the Sleep Clinic, Department of Otorhinolaryngology-Head and Neck Surgery. Flexible nasopharyngolaryngoscopy was performed in seated erect and supine position. Retropalatal and retroglossal regions were continuously recorded during quiet breathing and Mueller's maneuver in both positions. Captured images were measured using Scion Image software and narrowing rate was calculated. Level of each site was classified based on Fujita classification and severity of obstruction using Sher scoring system for Mueller's maneuver.
RESULTS: A total of 59 patients participated in this study. Twenty-nine (49.2%) participants had type 1 (retropalatal) obstruction, 23 (38.9%) had type 2 (retropalatal and retroglossal), and seven (11.9%) in type 3 (retroglossal) obstruction. Fifty (84.7%) of the patients have severe obstruction at the retropalatal region in supine position (SRP) followed by 35 (59.3%) at retropalatal region in erect position (ERP), 27 (45.8%) at retroglossal region in supine position (SRG) and eight (13.5%) at retroglossal region in erect position (ERG). The average oxygen saturation showed significant association in ERP (P = 0.012) and SRP (P < 0.001), but not significant in ERG and SRG.
CONCLUSIONS: Videoendoscopy utilizing flexible nasopharyngolaryngoscopy and Scion Image software is reliable, minimally invasive, and useful as an office procedure in evaluating the multilevel obstruction of upper airway in OSA patients. The retropalatal region has more severe obstruction compared with retroglossal region either in erect or supine position.

Matched MeSH terms: Oxygen/blood
Spatial assessment of Langat River water quality using chemometrics

Juahir H, Zain SM, Aris AZ, Yusoff MK, Mokhtar MB

J Environ Monit, 2010 Jan;12(1):287-95.
PMID: 20082024 DOI: 10.1039/b907306j

The present study deals with the assessment of Langat River water quality with some chemometrics approaches such as cluster and discriminant analysis coupled with an artificial neural network (ANN). The data used in this study were collected from seven monitoring stations under the river water quality monitoring program by the Department of Environment (DOE) from 1995 to 2002. Twenty three physico-chemical parameters were involved in this analysis. Cluster analysis successfully clustered the Langat River into three major clusters, namely high, moderate and less pollution regions. Discriminant analysis identified seven of the most significant parameters which contribute to the high variation of Langat River water quality, namely dissolved oxygen, biological oxygen demand, pH, ammoniacal nitrogen, chlorine, E. coli, and coliform. Discriminant analysis also plays an important role as an input selection parameter for an ANN of spatial prediction (pollution regions). The ANN showed better prediction performance in discriminating the regional area with an excellent percentage of correct classification compared to discriminant analysis. Multivariate analysis, coupled with ANN, is proposed, which could help in decision making and problem solving in the local environment.

Matched MeSH terms: Oxygen/analysis
Facial profile shape, malocclusion and palatal morphology in Malay obstructive sleep apnea patients

Banabilh SM, Samsudin AR, Suzina AH, Dinsuhaimi S

Angle Orthod, 2010 Jan;80(1):37-42.
PMID: 19852637 DOI: 10.2319/011509-26.1

To test the null hypothesis that there is no difference in facial profile shape, malocclusion class, or palatal morphology in Malay adults with and without obstructive sleep apnea (OSA).

Matched MeSH terms: Oxygen/blood
Strategies adopted by the mudskipper Boleophthalmus boddaerti to survive sulfide exposure in normoxia or hypoxia

Ip YK, Kuah SS, Chew SF

Physiol Biochem Zool, 2004 Sep-Oct;77(5):824-37.
PMID: 15547800

The effects of sulfide on the energy metabolism of Boleophthalmus boddaerti in normoxia and hypoxia were examined. The 24-, 48-, and 96-h LC50 values of sulfide for B. boddaerti with body weight ranging from 11.6 to 14.2 g were 0.786, 0.567, and 0.467 mM, respectively. The tolerance of B. boddaerti to sulfide was not due to the presence of a sulfide-insensitive cytochrome c oxidase. There was no accumulation of lactate in the muscle and liver of specimens exposed to sulfide in normoxia. In addition, the levels of ATP, AMP, and energy charge in both the muscle and the liver were unaffected. These results indicate that B. boddaerti was able to sustain the energy supply required for its metabolic needs via mainly aerobic respiration when exposed to sulfide (up to 0.4 mM) in normoxia. Exposure of B. boddaerti simultaneously to hypoxia and 0.2 mM sulfide for 48 h resulted in decreases in the ATP levels in the muscle and liver. However, the energy charge in both tissues remained unchanged, and the level of lactate accumulated in the muscle was too low to have any major contribution to the energy budget of the fish. Our results reveal that B. boddaerti possesses inducible mechanisms to detoxify sulfide in an ample supply or a lack of O2. In normoxia, it detoxified sulfide to sulfate, sulfite, and thiosulfate. There were significant increases in the activities of sulfide oxidase in the muscle and liver of specimens exposed to sulfide, with that in the liver being >13-fold higher than that in the muscle. However, in hypoxia, sulfide oxidase activity in the liver was suppressed in response to environmental sulfide. In such conditions, there were significant increases in the activities of sulfane sulfur-forming enzyme(s) in the muscle and liver that were not observed in specimens exposed to sulfide in normoxia. Correspondingly, there were no changes in the levels of sulfate or sulfite in the muscle or liver. Instead, B. boddaerti detoxified sulfide mainly to sulfane sulfur in hypoxia. In conclusion, B. boddaerti was able to activate different mechanisms to detoxify sulfide, producing different types of detoxification products in normoxia and hypoxia.

Matched MeSH terms: Oxygen/metabolism*
Fulltext New Peptide-Conjugated Chlorin-Type Photosensitizer Targeting Neuropilin-1 for Anti-Vascular Targeted Photodynamic Therapy

Kamarulzaman EE, Gazzali AM, Acherar S, Frochot C, Barberi-Heyob M, Boura C, et al.

Int J Mol Sci, 2015 Oct 12;16(10):24059-80.
PMID: 26473840 DOI: 10.3390/ijms161024059

Photodynamic therapy (PDT) is a cancer treatment modality that requires three components, namely light, dioxygen and a photosensitizing agent. After light excitation, the photosensitizer (PS) in its excited state transfers its energy to oxygen, which leads to photooxidation reactions. In order to improve the selectivity of the treatment, research has focused on the design of PS covalently attached to a tumor-targeting moiety. In this paper, we describe the synthesis and the physico-chemical and photophysical properties of six new peptide-conjugated photosensitizers designed for targeting the neuropilin-1 (NRP-1) receptor. We chose a TPC (5-(4-carboxyphenyl)-10,15, 20-triphenyl chlorine as photosensitizer, coupled via three different spacers (aminohexanoic acid, 1-amino-3,6-dioxaoctanoic acid, and 1-amino-9-aza-3,6,12,15-tetraoxa-10-on-heptadecanoic acid) to two different peptides (DKPPR and TKPRR). The affinity towards the NRP-1 receptor of the conjugated chlorins was evaluated along with in vitro and in vivo stability levels. The tissue concentration of the TPC-conjugates in animal model shows good distribution, especially for the DKPPR conjugates. The novel peptide-PS conjugates proposed in this study were proven to have potential to be further developed as future NRP-1 targeting photodynamic therapy agent.

Matched MeSH terms: Oxygen/chemistry
The Molecular Concept of Atheromatous Plaques

Thent ZC, Chakraborty C, Mahakkanukrauh P, Nik Ritza Kosai Nik Mahmood N, Rajan R, Das S

Curr Drug Targets, 2017;18(11):1250-1258.
PMID: 27138760 DOI: 10.2174/1389450117666160502151600

BACKGROUND: Recently, there are scientific attempts to discover new drugs in the biotechnology industry in order to treat various diseases including atherosclerosis.
OBJECTIVE: The main objective of the present review was to highlight the cellular, molecular biology and inflammatory process related to the atheromatous plaques.
METHODS: A thorough literature search of Pubmed, Google and Scopus databases was done.
RESULTS: Atherosclerosis is considered to be a leading cause of death throughout the world. Atherosclerosis involves oxidative damage to the cells with production of reactive oxygen species (ROS). Development of atheromatous plaques in the arterial wall is a common feature. Specific inflammatory markers pertaining to the arterial wall in atherosclerosis may be useful for both diagnosis and treatment. These include Nitric oxide (NO), cytokines, macrophage inhibiting factor (MIF), leucocytes and Pselectin. Modern therapeutic paradigms involving endothelial progenitor cells therapy, angiotensin II type-2 (AT<sub>2</sub>R) and ATP-activated purinergic receptor therapy are notable to mention.
CONCLUSION: Future drugs may be designed aiming three signalling mechanisms of AT<sub>2</sub>R which are (a) activation of protein phosphatases resulting in protein dephosphorylation (b) activation of bradykinin/nitric oxide/cyclic guanosine 3',5'-monophosphate pathway by vasodilation and (c) stimulation of phospholipase A(2) and release of arachidonic acid. Drugs may also be designed to act on ATP-activated purinergic receptor channel type P2X7 molecules which acts on cardiovascular system.

Matched MeSH terms: Reactive Oxygen Species/metabolism
Fulltext Sundarban Honey Confers Protection against Isoproterenol-Induced Myocardial Infarction in Wistar Rats

Afroz R, Tanvir EM, Karim N, Hossain MS, Alam N, Gan SH, et al.

Biomed Res Int, 2016;2016:6437641.
PMID: 27294126 DOI: 10.1155/2016/6437641

The present study was designed to investigate the cardioprotective effects of Sundarban honey (SH) in rats with isoproterenol- (ISO-) induced myocardial infarction. Adult male Wistar Albino rats were pretreated with Sundarban honey (5 g/kg) daily for a period of 6 weeks. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at 24 h intervals for 2 days. ISO-induced myocardial damage was indicated by increased serum cardiac specific troponin I levels and cardiac marker enzyme activities including creatine kinase-MB, lactate dehydrogenase, aspartate transaminase, and alanine transaminase. Significant increases in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol levels were also observed, along with a reduction in the serum high-density lipoprotein-cholesterol level. In addition to these diagnostic markers, the levels of lipid peroxide products were significantly increased. The activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly decreased in the hearts after ISO-induced myocardial infarction. However, pretreatment of ischemic rats with Sundarban honey brought the biochemical parameters to near normalcy, indicating the protective effect of Sundarban honey against ISO-induced ischemia in rats. Histopathological findings of the heart tissues further confirmed the biochemical findings, indicating that Sundarban honey confers protection against ISO-induced oxidative stress in the myocardium.

Matched MeSH terms: Reactive Oxygen Species/metabolism
CD26: A Prognostic Marker of Acute Lymphoblastic Leukemia in Children in the Post Remission Induction Phase

Mehde AA, Yusof F, Adel Mehdi W, Zainulabdeen JA

Asian Pac J Cancer Prev, 2015;16(12):5059-62.
PMID: 26163641

BACKGROUND: ALL is an irredeemable disease due to the resistance to treatment. There are several influences which are involved in such resistance to chemotherapy, including oxidative stress as a result of the generation of reactive oxygen species (ROS) and presence of hypodiploid cells. Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase-4, is a 110 kDa, multifunctional, membrane-bound glycoprotein.
AIM AND OBJECTIVES: The aim of this study was to evaluate the clinical significance of serum CD26 in patients with acute lymphoblastic leukaemia patients in the post remission induction phase, as well as the relationship between CD26 activity and the oxidative stress status.
MATERIALS AND METHODS: CD26, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), in addition to activity of related enzymes myeloperoxidase, glutathione- s-transferase and xanthine oxidase, were analysed in sixty children with acute lymphoblastic leukaemia in the post remission induction phase.
RESULTS: The study showed significant elevation in CD26, TOS and OSI levels in patients with acute lymphoblastic leukaemia in the post remission induction phase in comparison to healthy control samples. In contrast, myeloperoxidase, glutathione-s-transferase and xanthine oxidase activities were decreased significantly. A significant correlation between CD26 concentration and some oxidative stress parameters was evident in ALL patients.
CONCLUSIONS: Serum levels of CD26 appear to be useful as a new biomarker of oxidative stress in children with acute lymphoblastic leukaemia in the post remission induction phase, and levels of antioxidants must be regularly estimated during the treatment of children with ALL.

Matched MeSH terms: Reactive Oxygen Species/metabolism*
Synthetic indole Mannich bases: Their ability to modulate in vitro cellular immunity

Mesaik MA, Khan KM, Rahim F, Taha M, Haider SM, Perveen S, et al.

Bioorg Chem, 2015 Jun;60:118-22.
PMID: 26000491 DOI: 10.1016/j.bioorg.2015.05.003

The synthetic indole Mannich bases 1-13 have been investigated for their ability to modulate immune responses measured in vitro. These activities were based on monitoring their affects on T-lymphocyte proliferation, reactive oxygen species (ROS), IL (interleukin)-2, IL-4, and nitric oxide production. Compound 5 was found to be the most potent immunomodulator in this context. Four of the synthesized compounds, 5, 11, 12, and 13, have significant potent inhibitory effects on T-cell proliferation, IL-4, and nitric oxide production. However, none of the thirteen indole compounds exerted any activity against ROS production.

Matched MeSH terms: Reactive Oxygen Species/immunology
Fulltext Nanotoxic profiling of novel iron oxide nanoparticles functionalized with perchloric acid and SiPEG as a radiographic contrast medium

Mohamed MI, Mohammad MK, Abdul Razak HR, Abdul Razak K, Saad WM

Biomed Res Int, 2015;2015:183525.
PMID: 26075217 DOI: 10.1155/2015/183525

Emerging syntheses and findings of new metallic nanoparticles (MNPs) have become an important aspect in various fields including diagnostic imaging. To date, iodine has been utilized as a radiographic contrast medium. However, the raise concern of iodine threats on iodine-intolerance patient has led to search of new contrast media with lower toxic level. In this animal modeling study, 14 nm iron oxide nanoparticles (IONPs) with silane-polyethylene glycol (SiPEG) and perchloric acid have been assessed for toxicity level as compared to conventional iodine. The nanotoxicity of IONPs was evaluated in liver biochemistry, reactive oxygen species production (ROS), lipid peroxidation mechanism, and ultrastructural evaluation using transmission electron microscope (TEM). The hematological analysis and liver function test (LFT) revealed that most of the liver enzymes were significantly higher in iodine-administered group as compared to those in normal and IONPs groups (P < 0.05). ROS production assay and lipid peroxidation indicator, malondialdehyde (MDA), also showed significant reductions in comparison with iodine group (P < 0.05). TEM evaluation yielded the aberration of nucleus structure of iodine-administered group as compared to those in control and IONPs groups. This study has demonstrated the less toxic properties of IONPs and it may postulate that IONPs are safe to be applied as radiographic contrast medium.

Matched MeSH terms: Reactive Oxygen Species/metabolism
Nitric oxide contamination of hospital compressed air improves gas exchange in patients with acute lung injury

Tan PS, Genc F, Delgado E, Kellum JA, Pinsky MR

Intensive Care Med, 2002 Aug;28(8):1064-72.
PMID: 12185426

We tested the hypothesis that NO contamination of hospital compressed air also improves PaO(2) in patients with acute lung injury (ALI) and following lung transplant (LTx).

Matched MeSH terms: Oxygen/analysis*
Occurrence of the vanA and vanC2/C3 genes in Enterococcus species isolated from poultry sources in Malaysia

Radu S, Toosa H, Rahim RA, Reezal A, Ahmad M, Hamid AN, et al.

Diagn Microbiol Infect Dis, 2001 Mar;39(3):145-53.
PMID: 11337180

Enterococcus species isolated from poultry sources were characterized for their resistance to antibiotics, plasmid content, presence of van genes and their diversity by randomly amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR). The results showed that all isolates were multi-resistance to the antibiotics tested. Ampicillin (15/70) followed by chloramphenicol (37/70) were the most active antibiotics tested against the Enterococcus spp. isolates, while the overall resistant rates against the other antibiotics were between 64.3% to 100%. All vancomycin-resistant E. faecalis, E. durans, E. hirae and E. faecium isolates tested by the disk diffusion assay were positive in PCR detection for presence of vanA gene. All E. casseliflavus isolates were positive for vanC2/C3 gene. However, none of the Enterococcus spp. isolates were positive for vanB and vanC1 genes. Plasmids ranging in sizes between 1.1 to ca. 35.8 MDa were detected in 38/70 of the Enterococcus isolates. When the genetic relationship among all isolates of the individual species were tested by RAPD-PCR, genetic differences detected suggested a high genetic polymorphisms of isolates in each individual species. Our results indicates that further epidemiological studies are necessary to elucidate the role of food animals as reservoir of VRE and the public health significance of infections caused by Enterococcus spp.

Matched MeSH terms: Carbon-Oxygen Ligases/genetics*
The relationship between Helicobacter pylori and oxygen-derived free radicals in the mechanism of duodenal ulceration

Salim AS

Intern. Med., 1993 May;32(5):359-64.
PMID: 8400493

This prospective randomized study investigated the possibility that duodenal ulcer relapse associated with Helicobacter Pylori infection is mediated by oxygen-derived free radicals. To this end, the radical scavengers allopurinol (50 mg 4 times daily) and dimethyl sulphoxide (DMSO, 500 mg 4 times daily) were administered orally. One hundred and forty-six consecutive patients with previous symptomatic endoscopy proven duodenal ulceration, which had been shown endoscopically to have healed in the presence of gastric mucosal infection with Helicobacter Pylori, were randomized to receive for the period of one year either placebo, or cimetidine 400 mg at bedtime, or allopurinol, or DMSO. In one hundred and twenty-six patients evaluable for efficacy, the cumulative relapse at one year was: placebo 47%, cimetidine 24%, allopurinol 6% and DMSO 6%. Cimetidine was significantly effective in preventing the relapse (p < 0.01), however allopurinol and DMSO were superior to cimetidine in this respect (p < 0.05). In the patients who relapsed, ulcer recurrence tended to occur early in those on placebo and cimetidine and to be evenly distributed over the year in those on free radical scavenging therapy. In all groups, ulcer recurrence throughout the maintenance year was more frequently symptomatic than silent. The incidence of infection with Helicobacter Pylori was not influenced by any of the regimens employed and the bacterium was detected with every relapse noted in this study and during the follow-up endoscopy which was carried out at 6 months and at 12 months during the maintenance year. The results suggest that oxygen-derived free radicals are involved in the relapse of duodenal ulceration in patients infected with Helicobacter Pylori.

Matched MeSH terms: Reactive Oxygen Species/metabolism*
Fulltext Evaluation of Anti-proliferative Effects of Barringtonia racemosa and Gallic Acid on Caco-2 Cells

Ho IYM, Abdul Aziz A, Mat Junit S

Sci Rep, 2020 06 19;10(1):9987.
PMID: 32561807 DOI: 10.1038/s41598-020-66913-x

Barringtonia racemosa leaf water extract (BLE) had been shown to have high gallic acid (GA) content and BLE has been postulated to have anti-proliferative effects towards colorectal cancer. This study aims to further investigate the mechanism underlying the anti-proliferative effect of BLE in Caco-2 cells and to determine if GA is responsible for the observed effects. Both BLE and GA inhibited Caco-2 cells in a dose-dependent manner. Cells exposed to IC50 concentration of BLE and GA showed reduced antioxidant activities. GA-treated Caco-2 cells experienced higher oxidative stress compared to cells treated with BLE. Both BLE and GA significantly up-regulated the expression of SLC2A1. BLE but not GA, significantly down-regulated the expression of ADH4. Meanwhile, GA but not BLE, significantly up-regulated AKRIB10 and GLO1 but significantly down-regulated HAGH. Alterations in gene expression were coupled with changes in extracellular glucose and pyruvate levels. While BLE decreased intracellular pyruvate, GA did the opposite. Both intracellular and extracellular D-lactate were not affected by either BLE or GA. GA showed more pronounced effects on apoptosis while BLE irreversibly reduced cell percentage in the G0/G1 phase. In conclusion, this study demonstrates the multiple-actions of BLE against Caco-2 cells, potentially involving various polyphenolic compounds, including GA.

Matched MeSH terms: Reactive Oxygen Species/metabolism
Induction of ROS‑mediated cell death and activation of the JNK pathway by a sulfonamide derivative

Ahmad R, Vaali-Mohammed MA, Elwatidy M, Al-Obeed O, Al-Khayal K, Eldehna WM, et al.

Int J Mol Med, 2019 Jul 23.
PMID: 31364730 DOI: 10.3892/ijmm.2019.4284

The emergence of colorectal cancer in developed nations can be attributed to dietary habits, smoking, a sedentary lifestyle and obesity. Several treatment regimens are available for primary and metastatic colorectal cancer; however, these treatment options have had limited impact on cure and disease‑free survival, and novel agents need to be developed for treating colorectal cancer. Thus, the objective of this study was to explore the anticancer mechanism of a benzo(1,3)dioxol‑based derivative of sulfonamide. The compound's inhibitory effect on cell proliferation was determined using the MTT assay and the xCelligence RTDP machine. Alternations in the expression of Bcl‑2 and inhibitor of apoptosis protein families were detected by western blotting. Apoptotic marker protein expression, including cytochrome c and cleaved poly(ADP‑ribose)polymerase was measured in the cytosolic extract of cells. Apoptosis and necrosis were detected by flow cytometry and immunofluorescence. Reactive oxygen species (ROS), and activation of caspase‑3 and caspase‑7 were measured using flow cytometry. Activation of the JNK pathway was detected by western blotting. We investigated the molecular mechanism of action of the sulfonamide derivative on colorectal cancer cells and found that the compound possesses a potent anticancer effect, which is primarily exerted by inducing apoptosis and necrosis. Interestingly, this compound exhibited little antiproliferative effect against the normal colonic epithelial cell line FHC. Furthermore, our results showed that the compound could significantly increase ROS production. Apoptosis induction could be attenuated by the free oxygen radical scavenger N‑acetyl cysteine (NAC), indicating that the antiproliferative effect of this compound on colorectal cancer cells is at least partially dependent on the redox balance. In addition, JNK signaling was activated by treatment with this derivative, which led to the induction of apoptosis. On the contrary, a JNK inhibitor could suppress the cell death induced by this compound. Our findings thus suggested a novel anticancer mechanism of a benzo(1,3)dioxol‑based derivative of sulfonamide for colorectal cancer cells and may have therapeutic potential for the treatment of colorectal cancer; however, further investigation is required.

Matched MeSH terms: Oxygen; Reactive Oxygen Species
Fulltext Muscle oxygenation during hybrid arm and functional electrical stimulation-evoked leg cycling after spinal cord injury

Hasnan N, Mohamad Saadon NS, Hamzaid NA, Teoh MX, Ahmadi S, Davis GM

Medicine (Baltimore), 2018 Oct;97(43):e12922.
PMID: 30412097 DOI: 10.1097/MD.0000000000012922

This study compared muscle oxygenation (StO2) during arm cranking (ACE), functional electrical stimulation-evoked leg cycling (FES-LCE), and hybrid (ACE+FES-LCE) exercise in spinal cord injury individuals. Eight subjects with C7-T12 lesions performed exercises at 3 submaximal intensities. StO2 was measured during rest and exercise at 40%, 60%, and 80% of subjects' oxygen uptake (VO2) peak using near-infrared spectroscopy. StO2 of ACE showed a decrease whereas in ACE+FES-LCE, the arm muscles demonstrated increasing StO2 from rest in all of VO2) peak respectively. StO2 of FES-LCE displayed a decrease at 40% VO2 peak and steady increase for 60% and 80%, whereas ACE+FES-LCE revealed a steady increase from rest at all VO2 peak. ACE+FES-LCE elicited greater StO2 in both limbs which suggested that during this exercise, upper- and lower-limb muscles have higher blood flow and improved oxygenation compared to ACE or FES-LCE performed alone.

Matched MeSH terms: Oxygen Consumption/physiology*
The methanolic extract of Guibourtia tessmannii (caesalpiniaceae) and selenium modulate cytosolic calcium accumulation, apoptosis and oxidative stress in R2C tumour Leydig cells: Involvement of TRPV1 channels

Defo Deeh PB, Watcho P, Wankeu-Nya M, Ngadjui E, Usman UZ

Andrologia, 2019 Apr;51(3):e13216.
PMID: 30536879 DOI: 10.1111/and.13216

This study evaluated the effects of the methanolic extract of Guibourtia tessmannii (GT) and selenium (Se) on cell viability, intracellular calcium concentration ([Ca2+ ]i ), apoptosis and oxidative stress through transient receptor potential vanilloid 1 (TRPV1) channel activity in CCL-97 (R2C) tumour Leydig cells. The cells were divided into nine groups and treated as follows: (a)-Control, (b)-Capsazepine (CPZ, 0.1 mM, a TRPV1 channel blocker), (c)-Capsaicin (CAP, 0.01 mM, a TRPV1 channel activator), (d)-GT (500 μg/ml), (e)-GT+CPZ, (f)-GT+CAP, (g)-Se (200 nM), (h)-Se+CPZ and (i)-Se+CAP. After treatments, cell viability, [Ca2+ ]i , apoptosis, caspase 3/9, reactive oxygen species (ROS) and mitochondrial membrane depolarisation (MMD) were evaluated. The [Ca2+ ]i , apoptosis, caspase 3/9, MMD and ROS levels were significantly (p

Matched MeSH terms: Reactive Oxygen Species/metabolism

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