Mitochondrial Dependent Apoptosis: Ameliorative Effect of Flunarizine on Ischemia–Reperfusion of Celiac Artery-Induced Gastric Lesions in the Rat

Muthuraman, Arunachalam; Ramesh, Muthusamy; Chauhan, Ashish

doi:10.1007/s10620-011-1607-0

Cited by 11 publications

(5 citation statements)

References 49 publications

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“…TNF is an important mediator of the acute inflammatory response and is involved in the apoptosis of injured gastric mucosa by various agents, such as other proinflammatory cytokines [ 67 ]. Apoptosis is associated with a loss of mucosal integrity subjected to stress, impairment, and microvascular hemorrhage and plays an important role in the development of ulcers [ 68 ]. HCl/ethanol administration activates the innate immune system and promotes increased TNF levels in gastric tissue [ 69 ].…”

Section: Resultsmentioning

confidence: 99%

Antiulcer Activity and Potential Mechanism of Action of the Leaves of Spondias mombin L.

Brito

Almeida

Santana

et al. 2018

Oxidative Medicine and Cellular Longevity

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Spondias mombin L. is used in folk medicine for the treatment of inflammation and gastrointestinal diseases. Our study investigated the antiulcer activity of S. mombin ethanolic extract (SmEE) and its majority compounds gallic acid (GA) and ellagic acid (EA). Phytochemical characterization was performed by HPLC. The SmEE was screened for in vitro antioxidant activities using phosphomolybdenum, ABTS, DPPH, and FRAP assays. The antiulcer activity of SmEE, GA, EA, or GA + EA was evaluated by gastric lesion models induced by absolute ethanol and indomethacin. Following this, it is capable of stimulating mucus production, antisecretory capacity, and the influence of −SH groups and NO in the effect of SmEE. Its healing activity was demonstrated by acetic acid-induced chronic ulcer model. Anti-Helicobacter pylori activity was assessed by determining the MIC of the SmEE (64–1024 μg/mL). The HPLC results identified the presence of gallic acid and ellagic acid in SmEE. The extract showed antioxidant activity in vitro. SmEE (50, 100, and 200 mg/kg) reduced the area of ulcerative lesions induced by ethanol in 23.8, 90.3, and 90.2%, respectively. In NSAID model, the SmEE induced protection of 36.8, 49.4, and 49.9%, respectively. GA (10 mg/kg) or EA (7 mg/kg) or the association of GA + EA (10 + 7 mg/kg) inhibited the ethanol-induced lesions in 71.8, 70.9, and 94.9%, respectively, indicating synergistic action. SmEE (100 mg/kg) decreased acid secretion and H+ concentration in the gastric contents, increased levels of mucus, and showed to be dependent of −SH groups and NO on the protection of the gastric mucosa. In chronic ulcer model, SmEE reduced the gastric area lesion. SmEE showed anti-H. pylori activity. In conclusion, our study showed that SmEE has antiulcerogenic activity. GA and EA are isolated gastric protectors and, when associated, acted synergistically to protect the gastric mucosa.

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Section: Resultsmentioning

confidence: 99%

Antiulcer Activity and Potential Mechanism of Action of the Leaves of Spondias mombin L.

Brito

Almeida

Santana

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…Apoptosis induction is one of the mechanisms for inducing acute gastric lesion [95]. OME presented antiapoptotic effects (in vivo) associated with reduction of caspase 3 expression [90], as well as reduction of BAX [54] and mitochondrial calcium [96]. Other studies indicate that OME has antiapoptotic activity in 7 Oxidative Medicine and Cellular Longevity the gastric and intestinal tissues, showing reduction of lesions through antioxidant processes and anti-inflammatory activity through expression of Ntrk2 gene (inductor/inhibitor of cell proliferation) [97] and reduction of protein Egr1, which influences the increase of protein p53 [98].…”

Section: Antiapoptotic and Antinecrotic Effectsmentioning

confidence: 99%

“…Mitochondrial permeability transition pore is associated with apoptosis due to free radical production, calcium accumulation [99], and increase in mitochondrial ATP, which is linked to the maintenance of cellular respiration [96] and reduction of mitochondrial cytochrome C [100]. OME in gastric lesion models reduced ulcerative lesions [50], the incidence of gastric hemorrhages [101], prevented visible lesions with edema, erosions, and necrosis in gastric endothelial cells [102,103], and reduced vascular permeability [104].…”

Section: Antiapoptotic and Antinecrotic Effectsmentioning

confidence: 99%

Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer

Paz

Alencar

Lima

et al. 2020

Oxidative Medicine and Cellular Longevity

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Omeprazole (OME) is commonly used to treat gastrointestinal disorders. However, long-term use of OME can increase the risk of gastric cancer. We aimed to characterize the pharmacological effects of OME and to correlate its adverse effects and toxicogenetic risks to the genomic instability mechanisms and cancer-based on database reports. Thus, a search (till Aug 2019) was made in the PubMed, Scopus, and ScienceDirect with relevant keywords. Based on the study objective, we included 80 clinical reports, forty-six in vitro, and 76 in vivo studies. While controversial, the findings suggest that long-term use of OME (5 to 40 mg/kg) can induce genomic instability. On the other hand, OME-mediated protective effects are well reported and related to proton pump blockade and anti-inflammatory activity through an increase in gastric flow, anti-inflammatory markers (COX-2 and interleukins) and antiapoptotic markers (caspases and BCL-2), glycoprotein expression, and neutrophil infiltration reduction. The reported adverse and toxic effects, especially in clinical studies, were atrophic gastritis, cobalamin deficiencies, homeostasis disorders, polyp development, hepatotoxicity, cytotoxicity, and genotoxicity. This study highlights that OME may induce genomic instability and increase the risk of certain types of cancer. Therefore, adequate precautions should be taken, especially in its long-term therapeutic strategies and self-medication practices.

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“…Inflammatory cytokines, including TNF-α, have been postulated to play a role in gastric mucosal apoptosis [11] . Gastric mucosal apoptosis is known to be associated with the loss of mucosal integrity under many critical conditions such as stress, hemorrhage, microvascular leakage and may play an important role in ulcer development [12][13][14] . Endothelin, a 21 amino-acid peptide synthesized mainly by endothelial cells, exists in at least three isoforms: ET-1, ET-2, ET-3 [15,16] .…”

mentioning

confidence: 99%

Study on the antiulcer effects of Veronicastrum axillare on gastric ulcer in rats induced by ethanol based on tumor necrosis factor-α (TNF-α) and endothelin-1 (ET-1)

Du¹,

Zhao²,

Lu³

et al. 2013

Asian Pacific Journal of Tropical Biomedicine

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Mitochondrial Dependent Apoptosis: Ameliorative Effect of Flunarizine on Ischemia–Reperfusion of Celiac Artery-Induced Gastric Lesions in the Rat

Abstract: The gastroprotective effect of flunarizine may be produced due to its inactivation potential of mitochondrial permeability transition pore opening associated with anti-oxidative, calcium regulation along with its anti-apoptotic effect.

Cited by 11 publications

References 49 publications

Antiulcer Activity and Potential Mechanism of Action of the Leaves of Spondias mombin L.

Antiulcer Activity and Potential Mechanism of Action of the Leaves of Spondias mombin L.

Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer

Study on the antiulcer effects of Veronicastrum axillare on gastric ulcer in rats induced by ethanol based on tumor necrosis factor-α (TNF-α) and endothelin-1 (ET-1)

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