Protective effect of D-002, a mixture of beeswax alcohols, against indomethacin-induced gastric ulcers and mechanism of action

Pérez, Yohani; Oyarzábal, Ambar; Más, Rosa; Molina, Vivián; Jiménez, Sònia

doi:10.1007/s11418-012-0670-y

Cited by 36 publications

(43 citation statements)

References 39 publications

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“…It was reported that the oxidative stress in gastric tissue causes damage to key biomolecules such as lipids. In conjunction with the report of [64][65][66], the present study recorded elevations in the levels of the end products of lipid peroxidation, malondialdehyde (MDA) in the gastric tissues following SGU. The elevation in MDA suggests enhanced lipid peroxidation leading to tissue damage and failure of antioxidant defense mechanisms to prevent the formation of excessive free radicals.…”

Section: Discussionsupporting

confidence: 81%

Antiulcerogenic Efficacy of Ethanolic Extract of Vitis Vinifera Leaves in Rats

Sayed

Fahmy

Soliman

et al. 2016

Int J Pharm Pharm Sci

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Objective: The ethanolic extract of Vitis vinifera leaves (VVE) (500 mg/kg body weight), ranitidine (50 mg/kg body weight) and both of them were tested for their gastroprotective and curative effects against the incidence of peptic ulcer. Methods:The antiulcer effects of VVE were investigated using a combination of indomethacin and cold-stress for 2h. To ascertain the mechanism of action of VVE, its protective and curative effects were studied on gastric volume, gastric juice acidity, ulcer index and malondialdehyde (MDA), glutathione (GSH), catalase (CAT), glutathione-S-transferase (GST), superoxide dismutase (SOD), nitric oxide (NO) activities of both stomach and duodenum of rats. Moreover, histopathological effects on stomach and duodenum were determined. Results:The antioxidant activity of VVE was demonstrated using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) test. VVE was found to reduce the ulcer index, gastric volume and the level of gastric juice acidity. Also, VVE showed gastroprotective and curative activities mainly through improvement of antioxidant status and decreasing lipid peroxidation accompanied with amelioration of both stomach and duodenum architectures. Conclusion:The prophylactic and curative effects of VVE proved to be effective in preventing gastric and duodenal ulceration which may be probably due to its antioxidant and anti-acid secretory effects.

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Section: Discussionsupporting

confidence: 81%

Antiulcerogenic Efficacy of Ethanolic Extract of Vitis Vinifera Leaves in Rats

Sayed

Fahmy

Soliman

et al. 2016

Int J Pharm Pharm Sci

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“…The effect of D-002 200 and 400 mg/kg on leukocyte infiltration was greater than that OMP 20 mg/kg, but since only one dose of OMP was tested we cannot conclude that D-002 was more effective than OMP on such regard. These results should not be surprising since both D-002 [24] and OMP [35] have shown to produce anti-inflammatory effects on the gastric mucosa.…”

Section: Discussionmentioning

confidence: 77%

“…Nevertheless, in light of the role of the oxidative damage are critical in pathogenesis of RE [36] the antioxidant effects of D-002 [23,24,27] may contribute to the present results. In such regard, previous studies have demonstrated that the efficacy of D-002 for preventing indomethacin-induced gastric ulcers in rats was associated to the reduction of lipid peroxidation, [23,24] protein oxidation, generation of hydroxyl radical and to the increase of superoxide dismutase and glutathione peroxidase enzyme activities in gastric mucosa.…”

Section: Discussionmentioning

confidence: 97%

“…[20 -24] Devoid of acid suppressant effect, [20,21] the mechanisms of the gastroprotective action of D-002 involves the improved quality (content of proteins, glycoproteins, sulphated macromolecules) and increased secretion of gastric mucus, [21,22] anti-inflammatory and antioxidant effects on the gastric mucosa. [23,24] Oral administration of D-002 has demonstrated to reduce hydroxyl radicals, [21] malondialdehyde (MDA) [23,24] and carbonyl groups concentrations, and myeloperoxidase (MPO) activity in the rat gastric mucosa, and to increase the activity of antioxidant enzymes (glutathione peroxidase, superoxide dismutase and catalase). [24] Also, the ability of D-002 for inhibiting 5-lipoxygenase (5-LOX) [25] and to lower concentrations of leukotriene-B4 (LTB4), a gastrotoxic mediator, [26] could contribute to its gastroprotective effects.…”

Section: Introductionmentioning

confidence: 99%

“…[23,24] Oral administration of D-002 has demonstrated to reduce hydroxyl radicals, [21] malondialdehyde (MDA) [23,24] and carbonyl groups concentrations, and myeloperoxidase (MPO) activity in the rat gastric mucosa, and to increase the activity of antioxidant enzymes (glutathione peroxidase, superoxide dismutase and catalase). [24] Also, the ability of D-002 for inhibiting 5-lipoxygenase (5-LOX) [25] and to lower concentrations of leukotriene-B4 (LTB4), a gastrotoxic mediator, [26] could contribute to its gastroprotective effects.…”

Section: Introductionmentioning

confidence: 99%

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D-002 Ameliorates Histological Changes in Rats with Bile Reflux-Induced Esophagitis

Noa¹,

Más²,

Mendoza³

et al. 2017

IJPPE

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Abstract. Reflux esophagitis, a common gastrointestinal disease, may be induced by duodeno gastroesophageal-reflux, and by duodeno-esophageal reflux (DER), the reflux of the biliary content only. D-002, a mixture of six higher primary alcohols purified from the beeswax, has exhibited gastric and esophageal protection experimentally. The aim of this work was to investigate the effects of D-002 on the esophageal histological changes in rats with DER-induced esophagitis. Rats were randomized into six groups: a negative control and five with DER: a positive control, three D-002-(50, 200 and 400mg/kg, respectively) and one omeprazole (20 mg/kg) group, treated for 14 days. Microscopic studies of esophagus were performed looking for reflux esophagitis indicators, such as basal cell hyperproliferation, papillae elongation, inflammatory cell infiltrates, epithelial erosions and ulcerations. The thickness of esophageal epithelium was measured and leukocytes were counted. Histological characteristics of esophagitis were evaluated. Negative controls had normal esophagus, while positive controls exhibited marked esophagitis. The values of the histological score, thickness of the esophageal epithelium and leukocyte infiltration in the positive control group were higher (p <0.001) than in the negative control. D-002 (50 -400 mg/kg) reduced significantly (p <0.01) the histological scores versus the positive control group. D-002 lowered significantly the epithelium thickness and abolished (p <0.001) leukocytes infiltration versus the positive control. Compared with the positive control, omeprazole reduced (p <0.01) the histological score, the epithelium thickness and leukocytes infiltration. Repeated doses of D-002 ameliorated the histological changes in rats with DER-induced esophagitis.

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Protective activity of crocin against indomethacin-induced gastric lesions in rats

et al. 2015

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The present study was designed to elucidate the mechanism(s) of the gastro-protective effect of crocin against indomethacin-induced gastric lesions. Crocin or pantoprazole was administered to rats 30 min before indomethacin. Five hours later, the animals were killed and their stomachs were removed and examined macroscopically. Samples of gastric mucosa were collected for microscopic evaluation, mRNA expression of caspase-3, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 was quantified by RT-PCR, and protein levels of COX-1, COX-2, iNOS and caspase-3 were assessed by Western blotting. The pH, volume of gastric effluent and antioxidant activity were measured in 5 separate groups of rats following pylorus ligation. Indomethacin induced significant increases in mRNA and protein expression of iNOS and caspase-3 and increased MDA levels, and reduced the pH of the gastric effluent and protein and mRNA expression of COX-2 and protein expression of COX-1 and mucus content associated with gastric ulceration. Crocin and pantoprazole significantly inhibited mRNA and protein expression of iNOS, caspase-3 and MDA, and reduced mucus content induced by indomethacin. However, unlike pantoprazole, crocin failed to increase COX-1 and pH, but had variable increasing effects on mRNA and protein expression of COX-2. Macroscopic and microscopic observations showed that mucosal erosions induced by indomethacin were significantly inhibited by pantoprazole and crocin. These findings suggest that crocin exerts its gastro-protective effects mainly by inhibition of MDA, reduction in iNOS and caspase-3, and inhibition of the reduction in mucus content induced by indomethacin. Crocin is a novel agent that has potential in the prevention of ulceration induced by NSAIDs.

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Protective effect of D-002, a mixture of beeswax alcohols, against indomethacin-induced gastric ulcers and mechanism of action

Cited by 36 publications

References 39 publications

Antiulcerogenic Efficacy of Ethanolic Extract of Vitis Vinifera Leaves in Rats

Antiulcerogenic Efficacy of Ethanolic Extract of Vitis Vinifera Leaves in Rats

D-002 Ameliorates Histological Changes in Rats with Bile Reflux-Induced Esophagitis

Protective activity of crocin against indomethacin-induced gastric lesions in rats

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