Aggravating effect of atorvastatin on indomethacin-induced gastric injury: Focus on PGE2, TNF-α, neutrophils and iNOS

Yıldırım, Funda; Uyanik, Özge; Özyoğurtçu, Hande; Gürel, Aydın; Atukeren, Pınar; Gümüştaş, Koray; Özdemir, Osman; Uydeş-Doğan, Sönmez

doi:10.1016/j.prostaglandins.2015.07.002

Cited by 11 publications

(4 citation statements)

References 43 publications

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“…Experimental evidence indicated that the upregulation of NF-κB also induces the transcriptional activation of iNOS. 74 In the current study, we confirmed that HCl/EtOH- or INDO/HCl-induced gastric ulceration increased mucosal iNOS expression. In contrast, SR-5 administration effectively suppressed iNOS expression.…”

Section: Discussionsupporting

confidence: 82%

SR-5, the specific ratio of Korean multi-herbal formula: An evaluation of antiulcerogenic effects on experimentally induced gastric ulcers in mice

Kim¹,

Kim²,

Kang³

et al. 2021

Dose-Response

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Purpose Previously, we demonstrated that the specific ratio of Korean multi-herbal formula (SR-5) exhibits hepatoprotective properties against ethanol-induced hepatic damage in rats. Chronic and excessive alcohol consumption is a major etiological factor involved in gastric disease and ulcer development induced by the inflammatory response and oxidative stress. Methods The present study evaluated the gastroprotective effects of SR-5 (100, 150, and 200 mg/kg) against hydrochloride acid/ethanol (HCl/EtOH)-induced and indomethacin/hydrochloride acid (INDO/HCl)-induced gastritis in a mouse model and the mechanisms involved. Results All the tested doses of SR-5 significantly inhibited gastric lesions in the HCl/EtOH-induced ulcer model mice. Similarly, all the tested doses of SR-5 significantly inhibited gastric lesions in the INDO/HCl-induced ulcer model mice. Furthermore, mice pretreated with SR-5 had significantly increased gastric levels of enzymatic and nonenzymatic antioxidants, namely, catalase (CAT) and glutathione (GSH), with concomitant reductions in malondialdehyde (MDA) and reactive oxygen species (ROS) levels compared with those in the HCl/EtOH or INDO/HCl group. SR-5 suppressed the expression of nuclear factor-kappa B (NF-κB)/p65, inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) to their normal values. Conclusion These findings are the first to demonstrate the powerful protective effect of SR-5 against gastric injury development and provide hope for clinical application.

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Section: Discussionsupporting

confidence: 82%

SR-5, the specific ratio of Korean multi-herbal formula: An evaluation of antiulcerogenic effects on experimentally induced gastric ulcers in mice

Kim¹,

Kim²,

Kang³

et al. 2021

Dose-Response

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“…This inhibition of cyclooxygenase activity and PGE2 synthesis in gastric tissue is believed to be one of the main reasons for gastric injury induced by IND (Suleyman et al, 2010;Yadav et al, 2012). PGE2, a metabolite of arachidonic, participates in maintaining gastric mucosal defense and various gastrointestinal functions (Yildirim et al, 2015). After the administration of IND, the gastric tissue was obviously damaged, and COX-1 and COX-2 activities and PGE2 contents in gastric tissue decreased significantly.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Anwulignan on Gastric Injury Induced by Indomethacin in Mice

Liu

Fang

Zhang

et al. 2022

J Pharmacol Exp Ther

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Anwulignan (AN) is a monomer lignan from Schisandra sphenanthera Rehd. et Wits (Schisandra sphenanthera fructus, Schisandra sphenanthera). The protective effect of AN against the indomethacin (IND)-induced gastric injury to mice and the related mechanism of action was investigated in this study. The effect of AN was mainly assessed by observing the gastric tissue morphology, gastric ulcer index (GUI), ulcer inhibition rate (UIR), gastric juice volume (GJV) and pH value. Chemical colorimetry, immunofluorescence, ELISA, and Western blot were used to detect related factors in the gastric tissue. The results showed that AN reduced the GUI, increased the UIR, inhibited the GJV, and increased the gastric pH value. AN significantly increased cyclooxygenase-1, cyclooxygenase-2, and prostaglandin E2 expression levels in the gastric tissue, activated nuclear factor (erythroid-derived 2)-like 2 (Nrf2), increased heme oxygenase-1 expression, enhanced the activity of superoxide dismutase and glutathione peroxidase, and decreased the malondialdehyde content. AN reduced the phosphorylation of nuclear factor-k gene binding (NF-kB) p65 and its nuclear translocation, the key protein of NF-kB signaling pathway in the gastric tissue, and the content of the pathway downstream signaling molecules, including interleukin-6, interleukin-1b, and tumor necrosis factor-a, to play an anti-inflammatory role. AN inhibited the downstream signals B-cell lymphoma 2associated x protein and cleaved caspase-3 in gastric tissue, and activated B-cell lymphoma 2, to play an antiapoptotic role, which were further verified by Hoechst staining. Therefore, AN has a significant protection against the gastric injury induced by IND in mice, and the mechanism may be concerned in its activation of Nrf2, inhibition of NF-kB signaling pathway, and antiapoptotic effect. SIGNIFICANCE STATEMENTAnwulignan (AN) significantly reduced the indomethacininduced gastric injury in mice, and its antioxidation, antiinflammation, and antiapoptosis were considered to be involve in the effect, suggesting that AN should be a potential drug or food supplement for gastric injury induced by indomethacin.

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“…The link between oxidative stress and gastric ulcer is well recognized 23,24 . It is known that a reduction in blood supply to the gastric mucosa, accompanied by a build‐up of neutrophils in the gastric vascular endothelium, are triggered by NSAIDs resulting in ROS production and tissue necrosis 25,26 . Consequently, high levels of ROS contribute to lipid/protein/DNA oxidative damage, characterized by relevant biomarkers of NSAID‐induced lesions 9,27,28 and disruption of the integrity of epithelial and glandular gastric cells 29 .…”

Section: Discussionmentioning

confidence: 99%

Sildenafil attenuates nonsteroidal anti‐inflammatory‐induced gastric ulceration in mice via antioxidant and antigenotoxic mechanisms

Alves

Aires

Santos

et al. 2020

Clin Exp Pharma Physio

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Sildenafil (SIL) has potential as an interesting gastroprotective drug. However, the pathways of its protective effect still needs to be clarified, and its use as a potential gastroprotective agent validated. This study aims to evaluate the effects of SIL via modulation of oxidative stress in a NSAID‐induced gastric lesion model. Male Swiss mice were divided into six groups: control (CON, water), nonsteroidal anti‐inflammatory drug (NSAID, water), proton pump inhibitor (PPI, 30 mg/kg of lansoprazole), SIL 5 (5 mg/kg), SIL 25 (25 mg/kg) and SIL 50 (50 mg/kg). The animals were treated by gavage (a single dose) after 24 hours of fasting, and gastric lesions were performed after 30 minutes, with indomethacin (40 mg/kg, by gavage). After 6h, the animals were killed and the stomach was removed to evaluate reactive oxygen species (ROS) production, oxidation of macromolecules, quantification of antioxidant enzymes, DNA fragmentation, apoptosis and macroscopic and histologic analysis of gastric lesions. SIL exerts a dose‐dependent gastroprotective effect against NSAID‐induced mucosal injury, also reducing cytoplasmic levels of ROS and consequent oxidative damage to macromolecules. In addition, SIL increases nitric oxide bioavailability, antioxidant enzymes and gastric cellular viability, as well as restoring important factors involved in gastroprotection. Our results demonstrate that different doses of SIL prevent indomethacin‐induced gastric ulcer in mice via different, but complementary antioxidant, antigenotoxic and antiapoptotic mechanisms.

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Aggravating effect of atorvastatin on indomethacin-induced gastric injury: Focus on PGE2, TNF-α, neutrophils and iNOS

Cited by 11 publications

References 43 publications

SR-5, the specific ratio of Korean multi-herbal formula: An evaluation of antiulcerogenic effects on experimentally induced gastric ulcers in mice

SR-5, the specific ratio of Korean multi-herbal formula: An evaluation of antiulcerogenic effects on experimentally induced gastric ulcers in mice

Protective Effect of Anwulignan on Gastric Injury Induced by Indomethacin in Mice

Sildenafil attenuates nonsteroidal anti‐inflammatory‐induced gastric ulceration in mice via antioxidant and antigenotoxic mechanisms

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