Protection against stress-induced acute gastric mucosal injury by free radical scavengers

Salim, Aws S.

doi:10.1007/bf01690766

Cited by 32 publications

(20 citation statements)

References 21 publications

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“…However, ischemia may also cause apoptosis through other mechanisms such as involvement of Bcl-2, Bax, and c-Fos proteins (74,75). Excessive generation of nitric oxide by gastric mucosal-inducible nitricoxide synthase by stress also promotes apoptosis through increased formation of ROS (76,77). That ROS can cause oxidative damage of DNA isolated from both rat and human gastric mucosal epithelial cells has been evident from our in vitro studies where incubation of DNA with an ⅐ OH-generating system (22,59,78) causes extensive DNA degradation, which is sensitive to catalase and DMPO.…”

Section: Discussionmentioning

confidence: 99%

A Novel Antioxidant and Antiapoptotic Role of Omeprazole to Block Gastric Ulcer through Scavenging of Hydroxyl Radical

Biswas¹,

Bandyopadhyay²,

Chattopadhyay³

et al. 2003

Journal of Biological Chemistry

257

199

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The mechanism of the antiulcer effect of omeprazole was studied placing emphasis on its role to block oxidative damage and apoptosis during ulceration. Dose-response studies on gastroprotection in stress and indomethacin-induced ulcer and inhibition of pylorus ligation-induced acid secretion indicate that omeprazole significantly blocks gastric lesions at lower dose (2.5 mg/kg) without inhibiting acid secretion, suggesting an independent mechanism for its antiulcer effect. Time course studies on gastroprotection and acid reduction also indicate that omeprazole almost completely blocks lesions at 1 h when acid inhibition is partial. The severity of lesions correlates well with the increased level of endogenous hydroxyl radical ( ⅐ OH), which when scavenged by dimethyl sulfoxide causes around 90% reduction of the lesions, indicating that ⅐ OH plays a major role in gastric damage. Omeprazole blocks stress-induced increased generation of ⅐ OH and associated lipid peroxidation and protein oxidation, indicating that its antioxidant role plays a major part in preventing oxidative damage. Omeprazole also prevents stress-induced DNA fragmentation, suggesting its antiapoptotic role to block cell death during ulceration. The oxidative damage of DNA by ⅐ OH generated in vitro is also protected by omeprazole or its analogue, lansoprazole. Lansoprazole when incubated in a ⅐ OH-generating system scavenges ⅐ OH to produce four oxidation products of which the major one in mass spectroscopy shows a molecular ion peak at m/z 385, which is 16 mass units higher than that of lansoprazole (m/z 369). The product shows no additional aromatic proton signal for aromatic hydroxylation in 1 H NMR. The product absorbing at 278 nm shows no alkaline shift for phenols, thereby excluding the formation of hydroxylansoprazole. The product is assigned to lansoprazole sulfone formed by the addition of one oxygen atom at the sulfur center following attack by the ⅐ OH. Thus, omeprazole plays a significant role in gastroprotection by acting as a potent antioxidant and antiapoptotic molecule.

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Section: Discussionmentioning

confidence: 99%

A Novel Antioxidant and Antiapoptotic Role of Omeprazole to Block Gastric Ulcer through Scavenging of Hydroxyl Radical

Biswas¹,

Bandyopadhyay²,

Chattopadhyay³

et al. 2003

Journal of Biological Chemistry

257

199

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“…The fact that DMSO significantly reduced the bacterial load and enhanced the survival rate of the burned mice infected with P. aeruginosa is remarkable. DMSO has been used to treat many illnesses in humans, including dermatologic diseases (21), gastrointestinal disorders (24)(25)(26)(27), wound healing (6), pulmonary conditions (28,29), and interstitial cystitis (IC) (62). However, its usefulness has, in most cases, been controversial, and the only FDA-approved use is for the treatment of interstitial cystitis.…”

Section: Figmentioning

confidence: 99%

“…Besides its cryoprotective and tissue penetration-enhancing actions, DMSO has been used to treat numerous conditions and ailments in preclinical research and, in some cases, clinical situations. The conditions treated include dermatologic diseases (21), pain (22), chronic prostatitis (23), gastrointestinal disorders (24)(25)(26)(27), wound healing (6), pulmonary fibrosis and amyloidosis (28,29), and interstitial cystitis (IC) (30), even though in most cases the pharmacological mechanisms are unknown.…”

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confidence: 99%

Potential Use of Dimethyl Sulfoxide in Treatment of Infections Caused by Pseudomonas aeruginosa

Qiao

Bai

et al. 2016

Antimicrob Agents Chemother

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c Dimethyl sulfoxide (DMSO) is commonly used as a solvent to dissolve water-insoluble drugs or other test samples in both in vivo and in vitro experiments. It was observed during our experiment that DMSO at noninhibitory concentrations could significantly inhibit pyocyanin production in the human pathogen Pseudomonas aeruginosa. Pyocyanin is an important pathogenic factor whose production is controlled by a cell density-dependent quorum-sensing (QS) system. Investigation of the effect of DMSO on QS showed that DMSO has significant QS antagonistic activities and concentrations of DMSO in the micromolar range attenuated a battery of QS-controlled virulence factors, including rhamnolipid, elastase, and LasA protease production and biofilm formation. Further study indicated that DMSO inhibition of biofilm formation and pyocyanin production was attained by reducing the level of production of an autoinducer molecule of the rhl QS system, N-butanoyl-L-homoserine lactone (C 4 -HSL). In a mouse model of a burn wound infection with P. aeruginosa, treatment with DMSO significantly decreased mouse mortality compared with that for mice in the control group. The capacity of DMSO to attenuate the pathogenicity of P. aeruginosa points to the potential use of DMSO as an antipathogenic agent for the treatment of P. aeruginosa infection. As a commonly used solvent, however, DMSO's impact on bacterial virulence calls for cautionary attention in its usage in biological, medicinal, and clinical studies. Pseudomonas aeruginosa is a prevalent opportunistic pathogen capable of causing various infections in humans, including pneumonia and urinary tract infections, bloodstream infections, and infections in burn patients (1). The chronic infection caused by P. aeruginosa and the associated pulmonary inflammation are ultimately responsible for the majority of cases of mortality in patients with cystic fibrosis (2). The ability of P. aeruginosa to cause diverse infections is attributed to its myriad virulence factors and biofilm-forming capability, which are controlled by the intercellular quorum-sensing (QS) communication system (3-5).P. aeruginosa has two acyl-homoserine lactone (AHL)-mediated QS systems, known as the las and rhl QS systems. The las and rhl systems consist of the transcriptional activators LasR and RhlR, respectively, and the signal synthases LasI and RhlI, respectively. The major signals in the las and rhl systems are N-(3-oxododecanoyl)-HSL (3-oxo-C 12 -HSL) and N-butanoyl-L-homoserine lactone (C 4 -HSL), respectively (5). P. aeruginosa employs these QS systems to control a wide range of extracellular virulence factors, including pyocyanin, elastase, and rhamnolipid (7-12). The AHL-mediated QS systems also play a crucial role in biofilm formation by P. aeruginosa, a common cause of resistance to antibiotics and the difficulties with the treatment of infections (13). The las system influences the activation of pel and, accordingly, biofilm matrix formation (14), and the rhl system contributes to the maintenance of the bio...

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“…23,24 In order to explore the potential involvement of antioxidant defenses in the gastroprotective property of PO, the antioxidant activities (SOD, CAT, and GSH) and lipid peroxidation levels (MDA) were probed. The data are summarized in Table 2.…”

Section: Antioxidant Activitymentioning

confidence: 99%

The gastroprotective effect of pogostone from Pogostemonis Herba against indomethacin-induced gastric ulcer in rats

Chen

Liu

et al. 2015

Exp Biol Med (Maywood)

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Pogostemonis Herba, known as ''Guang-Huo-Xiang'' in Chinese, has been widely used in the treatment of gastrointestinal dysfunction. Pogostone is one of the major constituents of Pogostemonis Herba. The aim was to scientifically evaluate the possible gastroprotective effect and the underlying mechanisms of pogostone against indomethacin-induced gastric ulcer in rats. Rats were orally treated with vehicle, lansoprazole (30 mg/kg) or pogostone (10, 20 and 40 mg/kg) and subsequently exposed to acute gastric lesions induced by indomethacin. Gross evaluation, histological observation, gastric mucosal superoxide dismutase activity, glutathione content, catalase activity, malonaldehyde level and prostaglandin E2 production were performed. Immunohistochemistry and reverse transcription polymerase chain reaction for cyclooxygenase-1 and cyclooxygenase-2, as well as terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay, immunohistochemistry for heat-shock protein 70, B-cell lymphoma-2 and Bax were conducted. Results indicated that rats pretreated with pogostone showed remarkable protection from the gastric mucosa damage compared to vehicle-treated rats based on the ulcer index and inhibition percentage. Histologically, oral administration of pogostone resulted in observable improvement of gastric injury, characterized by reduction of necrotic lesion, flattening of gastric mucosa and alleviation of submucosal edema with hemorrhage. Pogostone pretreatment significantly raised the depressed activities of superoxide dismutase, glutathione and catalase, while reduced the elevated malonaldehyde level compared with indomethacin-induced group. Pogostone-pretreated group induced a significant increase in gastric mucosal prostaglandin E2 level and obvious up-regulation of protein levels and mRNA expressions of cyclooxygenase-1 and cyclooxygenase-2. Furthermore, antiapoptotic effect of pogostone was verified by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay, and the apoptotic process triggered by pogostone involved the up-expression of heat-shock protein70 and B-cell lymphoma-2 protein, and suppression of Bax protein expressions in the ulcerated tissues. It is speculated that the gastroprotective effect of pogostone against indomethacin-induced gastric ulceration might be associated with its stimulation of cyclooxygenase-mediated prostaglandin E2, antioxidant and antiapoptotic effect.

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Protection against stress-induced acute gastric mucosal injury by free radical scavengers

Cited by 32 publications

References 21 publications

A Novel Antioxidant and Antiapoptotic Role of Omeprazole to Block Gastric Ulcer through Scavenging of Hydroxyl Radical

A Novel Antioxidant and Antiapoptotic Role of Omeprazole to Block Gastric Ulcer through Scavenging of Hydroxyl Radical

Potential Use of Dimethyl Sulfoxide in Treatment of Infections Caused by Pseudomonas aeruginosa

The gastroprotective effect of pogostone from Pogostemonis Herba against indomethacin-induced gastric ulcer in rats

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