Effect of quercetin, flavonoids and α-tocopherol, an antioxidant vitamin on experimental reflux oesophagitis in rats

Rao, Chandana Venkateswara; Vijayakumar, M.

doi:10.1016/j.ejphar.2008.04.062

Cited by 48 publications

(36 citation statements)

References 35 publications

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“…37 Quercetin, another Nrf2 activator, 38 enhanced intestinal barrier function through upregulation of Cldn4 in Caco-2 cells. [39][40][41] In summary, our data suggested that Nrf2 deficiency caused mitochondrial dysfunction, downregulated Cldn4 and ultimately impaired energy-dependent tight junction in the oesophageal epithelium.…”

Section: Discussionmentioning

confidence: 64%

Nrf2 deficiency impairs the barrier function of mouse oesophageal epithelium

Chen

et al. 2013

Gut

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Objective As a major cellular defense mechanism, the Nrf2/Keap1 pathway regulates expression of genes involved in detoxification and stress response. Our previous study revealed activation of the Nrf2/Keap1 pathway at the maturation phase during mouse esophageal development, suggesting a potential function in epithelial defense. Here we hypothesize that Nrf2 is involved in the barrier function of esophageal epithelium, and plays a protective role against gastroesophageal reflux disease (GERD). Design Human esophageal biopsy samples, mouse surgical models and Nrf2-/- mice were used to assess the role of the Nrf2/Keap1 pathway in esophageal mucosal barrier function. Trans-epithelial electrical resistance (TEER) was measured with mini-Ussing chambers. Hematoxylin and eosin (HE) staining and transmission electron microscopy were used to examine cell morphology, while gene microarray, immunohistochemistry, Western blotting and ChIP analysis were used to assess the expression of pathway genes. Results Nrf2 was expressed in normal esophageal epithelium and activated in GERD of both humans and mice. Nrf2 deficiency and gastroesophageal reflux in mice, either alone or in combination, reduced TEER and increased intercellular space diameter in esophageal epithelium. Nrf2 target genes and gene sets associated with oxidoreductase activity, mitochondrial biogenesis and energy production were down-regulated in the esophageal epithelium of Nrf2-/- mice. Consistent with the antioxidative function of Nrf2, a DNA oxidative damage marker (8OHdG) dramatically increased in esophageal epithelial cells of Nrf2-/- mice compared with those of wild-type mice. Interestingly, ATP biogenesis, Cox IV (a mitochondrial protein) and Claudin-4 (Cldn4) expression were down-regulated in the esophageal epithelium of Nrf2-/- mice, suggesting that energy-dependent tight junction integrity was subject to Nrf2 regulation. ChIP analysis confirmed the binding of Nrf2 to Cldn4 promoter. Conclusion Nrf2 deficiency impairs esophageal barrier function through disrupting energy-dependent tight junction. Elucidating the role of this pathway in GERD has potential implications for the pathogenesis and therapy of the disease.

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Section: Discussionmentioning

confidence: 64%

Nrf2 deficiency impairs the barrier function of mouse oesophageal epithelium

Chen

et al. 2013

Gut

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“…The phytochemical composition of MBI (mainly flavonoids) is probably involved in this result because a study by Rao and Vijayakumar (2008) has already described the effect of (+)-catechin, the main flavan-3-ol present in MBI, as an important gastroprotective compound against gastric mucosal injury induced by ischemia-reperfusion in rats.…”

Section: Tablementioning

confidence: 94%

Byrsonima intermedia A. Juss.: Gastric and duodenal anti-ulcer, antimicrobial and antidiarrheal effects in experimental rodent models

Santos

Kushima

Rodrigues

et al. 2012

Journal of Ethnopharmacology

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“…α-tocopherol is the most potent antioxidant that can break the propagation of the free radical chain reaction in the lipid part of the biological membrane. Chandana and Madhavan [20] reported that α-tocopherol has efficacy to esophagitis. Thus, we attempted to determine any anti-esophagitis effects of LF in a rat model of RE induced by pylorus and forestomach ligation.…”

Section: Discussionmentioning

confidence: 99%

Effect of Lonicerae Flos extracts on reflux esophagitis with antioxidant activity

Ku¹,

Seo²,

Park³

et al. 2009

WJG

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AIM:To observe the effects of traditional antiinflammatory medicine Lonicerae Flos (LF) on rat reflux esophagitis (RE) induced by pylorus and forestomach ligation compared with the well-known proton antioxidant, α-tocopherol. M E T H O D S: R a t s w e r e p r e t r e a t e d w i t h t h r e e different dosages of LF (500, 250 and 125 mg/kg) orally, once a day for 14 d before pylorus and forestomach ligation. Nine hours after pylorus and forestomach ligation, changes to the stomach and esophagus lesion areas, gastric volumes, acid and pepsin outputs, antioxidant effects, esophageal lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), myeloperoxidase and glutathione (GSH) levels, and collagen contents (marker of flexibility) were observed on the esophageal and fundic histopathology. The results were compared with an α-tocopherol (once orally, 1 h before operation, 30 mg/kg) treated group in which the effects on RE were already confirmed. RESULTS:Pylorus and forestomach ligations caused marked increases of gross esophageal and gastric mucosa lesion areas, which corresponded with histopathological changes. In addition, increases of esophageal lipid peroxidation, decreases of SOD, CAT, and GSH-free radical scavengers, increases of collagen were observed. However, these pylorus and forestomach ligation induced RE were dose-dependently inhibited by treatment of 500, 250 and 125 mg/kg of LF extract, mediated by antioxidant effects. RE at 250 mg/kg showed similar effects α-tocopherol. CONCLUSION:The results suggest that antioxidant effects of LF could attenuate the severity of RE and prevent the esophageal mucosal damage, and validate its therapeutic use in esophageal reflux disease.

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Effect of quercetin, flavonoids and α-tocopherol, an antioxidant vitamin on experimental reflux oesophagitis in rats

Cited by 48 publications

References 35 publications

Nrf2 deficiency impairs the barrier function of mouse oesophageal epithelium

Nrf2 deficiency impairs the barrier function of mouse oesophageal epithelium

Byrsonima intermedia A. Juss.: Gastric and duodenal anti-ulcer, antimicrobial and antidiarrheal effects in experimental rodent models

Effect of Lonicerae Flos extracts on reflux esophagitis with antioxidant activity

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