Protective Effects of Simvastatin Against Alendronate-Induced Gastric Mucosal Injury in Rats

Carvalho, Nathalia S.; Silva, Mônica M.; Silva, Renan O.; Nicolau, Lucas A.D.; Araújo, Thiago Souza; Costa, Douglas Soares da; Sousa, Nayara Alves de; Souza, Luan Kelves Miranda de; Soares, Pedro Marcos Gomes; Medeiros, Jand Venes R.

doi:10.1007/s10620-015-3890-7

Cited by 12 publications

(12 citation statements)

References 49 publications

(57 reference statements)

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“…In our study, we adapted experimental model of alendronate-induced gastric damage [ 40 ], and we confirmed that this drug when administered orally in graded concentrations caused macroscopic lesions in the rat stomach. Our results are corroborative with previous observations that various BPs evoke mainly antral lesions accompanied by severe edema, neutrophil accumulation, and epithelial cell loss determined microscopically [ 50 – 52 ].…”

Section: Discussionsupporting

confidence: 93%

Hydrogen Sulfide and Carbon Monoxide Protect Gastric Mucosa Compromised by Mild Stress Against Alendronate Injury

et al. 2016

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BackgroundAlendronate is an inhibitor of osteoclast-mediated bone resorption, but its clinical utility is limited due to gastrointestinal complications including bleeding erosions.AimsWe studied whether potent vasodilators hydrogen sulfide (H2S) and carbon monoxide (CO) can protect against alendronate-induced gastric lesions in rats exposed to mild stress.MethodsThree series (A, B, and C) of Wistar rats received alendronate (150–700 mg/kg i.g., series A) with or without NaHS (5 mg/kg), H2S donor or CORM-2 (5 mg/kg) releasing CO administered i.g. 30 min before alendronate administration (series B) in rats exposed for 3 days before alendronate administration to mild stress (series C). The area of gastric lesions was assessed by planimetry, the gastric blood flow (GBF) was determined by H2-gas clearance technique, and H2S production via CSE/CBS/3-MST activity and the gastric expression of HO-1, HO-2, HIF-1α, NF-κB, iNOS, COX-2, IL-1β, TNF-α, GPx-1 and SOD-2 were analyzed by qPCR or Western blot.ResultsAlendronate dose-dependently produced gastric mucosal lesions and significantly decreased GBF, and these effects were exacerbated by mild stress. NaHS and CORM-2 significantly reduced the alendronate-induced gastric lesions in non-stressed and stressed animals, but only NaHS but not CORM-2 raised H2S production. NaHS and CORM-2 inhibited gastric expression of HIF-1α protein and HO-1, HIF-1α, NF-κB, COX-2, iNOS, IL-1β, TNF-α mRNAs but failed to affect those of HO-2, GPx-1, and SOD-2.ConclusionBoth H2S and CO released from their donors, NaHS and CORM-2, protect gastric mucosa compromised by stress against alendronate-induced gastric damage via mechanism involving downregulation of HIF-1α, NF-κB and proinflammatory factors COX-2, iNOS, IL-1β, and TNF-α.

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Section: Discussionsupporting

confidence: 93%

Hydrogen Sulfide and Carbon Monoxide Protect Gastric Mucosa Compromised by Mild Stress Against Alendronate Injury

et al. 2016

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“…In addition, alendronate induces TNF-α and IL-1ß response and pro-inflammatory cytokines in the mucosa resulting in inflammation, subepithelial edema and sloughing of the epithelium or ulcer formation. Moreover, when alendronate is applied to the mucosa, it decreases trans-mucosal potential difference which is suggestive of a direct disruption of the surface epithelial cells [27] . In the present study, marked depletion of mucus secretion in the duodenal mucosa of Fosamax-treated group occurred, as evidenced by marked depletion of PAS-positive material.…”

Section: Discussionmentioning

confidence: 97%

“…Lipid peroxidation induced by reactive oxygen metabolites and glutathione depletion is believed to be an important cause of gastrointestinal mucosal damage. It has been reported that at pH<2, alendronate is converted to alendronic acid, which is more irritating to mucosa than the alendronate [9,27] . Since in the present work, Fosamax was administered orally in fasted rats, it seems likely that the mucosal damage is due to the direct irritating effect of alendronate in its acid form.…”

Section: Discussionmentioning

confidence: 99%

Effect of Fosamax on the duodenal mucosa in adult male albino rats and the possible protection by nigella sativa oil: a histological and immunohistochemical study

Kassab

2019

Egyptian Journal of Histology

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Background: Fosamax, an oral bisphosphonate, is the most commonly prescribed drug for the treatment of various bones diseases. However, Fosamax therapy is associated with gastrointestinal toxicity that influences the treatment compliance. Nigella sativa (N sativa) is an annual herbaceous plant and have been safely used as a natural remedy in Egypt. It has a wide range of pharmacological activities and a proposed role in combating many gastrointestinal disorders. Aim: This work aimed to study the effect of Fosamax on the histological structure of the duodenal mucosa of albino rats and to evaluate the possible protective role of nigella sativa oil. Materials and methods: Forty adult male albino rats were divided into four equal groups: the control group, the N sativa oil-treated group (2.5 ml/kg), the Fosamax-treated group (0.05mg/kg), and both Fosamax and N sativa oil-treated group. Treatments were given orally once weekly for 13 weeks. Specimens from the duodenum were processed for light microscopy. Immunohistochemical study was carried out using antibodies against nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and Ki67 protein. Results: Specimens from Fosamax-treated rats showed a statistically significant decrease in the duodenal mucosal thickness. The lining epithelium showed nuclear alteration and vacuolated cytoplasm and there was mononuclear cellular infiltration. The immunohistochemical study of Fosamax-treated group showed a significant increase in NF-kB, COX-2 and Bax immunoreaction and a significant decrease in Bcl-2 and Ki67 expression. In contrast, minimal changes were observed in rats treated concomitantly with both Fosamax and N sativa oil with non-significant changes in the immunoreactions compared with the control group. Conclusion: Fosamax induced structural changes in the duodenal mucosa of adult albino rats, which could be ameliorated by concomitant treatment with nigella sativa oil.

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“…Regarding the occurrence of cytoplasmic vacuolations of acinar and duct cells; many authors documented that alendronate reduce the mitochondrial membrane potential leading to generation of Reactive Oxygen Species (ROS) and free radicals resulting in lipid peroxidation and damage of cell membranes as well as membranes of the cell organelles ending in failure of the energy-dependent Na+ K + ion pumps in the cell [29][30][31] .…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the abnormal shaped mitochondria with lost cristae and dilated intercellular space were observed as an EM results in the present work. These findings may be attributed to the release of ROS, causing disturbance of the plasma membrane integrity, and consequently beside edema, could disrupt the intercellular junctions [29,37] . Too, electron dense bodies of variable sizes and heterogeneous consistency in the cytoplasm of acinar and duct cells were recorded.…”

Section: Discussionmentioning

confidence: 99%

Histological and Immunohistochemical Study of the Effect of Alendronate on the Submandibular Salivary Gland of Adult Male Albino Rat and the Possible Protective Effect of Propolis

El-Yazed¹,

El-Sayed

Elbakary

et al. 2018

The Medical Journal of Cairo University

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Background: Alendronate is an anti-bone-resorptive drug used in the treatment of post-menopausal osteoporosis. Its long administration induced organ damage especially the submandibular salivary glands. Propolis is a natural resinous substance with an antioxidant and anti-inflammatory actions. Aim of Study:This work was performed to study the effect of alendronate on the histological structure of the submandibular salivary gland of adult male albino rat and the possible protective effect of propolis.Material and Methods: 40 adult male albino rats were divided into 4 groups (10 rats each); control group, Group A: Rats received 100mg/kg body weight propolis, Group B: Rats received 2.5mg/kg body weight alendronate and Group C: Rats received propolis 30 minutes before alendronate. Doses were given orally for consecutive 30 days then gland specimens were taken for histological and immunohistochemical studies using light and electron microscopes.Results: H & E and toluidine blue results of Group B revealed disturbed architecture, separated lobules and acini, cytoplasmic vacuolations, dark nuclei, irregular ducts and congested blood vessels. PAS-AB showed significant increase in its mean color intensity as compared with control group while a-SMA glandular myoepithelial cells immunostaining expressed significant decrease in its mean color intensity in comparison to control group. Electron microscopic examination of acinar and duct cells revealed cytoplasmic vacuolations, rarefaction, abnormal shaped mitochondria with lost cristae, electron dense bodies, dilated RER and Golgi apparatus, apparently increased secretory granules with coalescence, compressed shrunken hyperchromatic nuclei, nuclear membrane irregularities, and dilated perinuclear and intercellular spaces. Group C showed moderate improvement of the previous pathological findings.Conclusion: Alendronate induced damaging effects on the histological structure of submandibular salivary gland in Egypt rats and the administration of propolis could moderately improve such damage through its anti-oxidant and antiinflammatory effects.

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Protective Effects of Simvastatin Against Alendronate-Induced Gastric Mucosal Injury in Rats

Cited by 12 publications

References 49 publications

Hydrogen Sulfide and Carbon Monoxide Protect Gastric Mucosa Compromised by Mild Stress Against Alendronate Injury

Hydrogen Sulfide and Carbon Monoxide Protect Gastric Mucosa Compromised by Mild Stress Against Alendronate Injury

Effect of Fosamax on the duodenal mucosa in adult male albino rats and the possible protection by nigella sativa oil: a histological and immunohistochemical study

Histological and Immunohistochemical Study of the Effect of Alendronate on the Submandibular Salivary Gland of Adult Male Albino Rat and the Possible Protective Effect of Propolis

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