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Hydrogen Sulfide and Carbon Monoxide Protect Gastric Mucosa Compromised by Mild Stress Against Alendronate Injury.
Dig Dis Sci. 2016 11; 61(11):3176-3189.DD

Abstract

BACKGROUND

Alendronate is an inhibitor of osteoclast-mediated bone resorption, but its clinical utility is limited due to gastrointestinal complications including bleeding erosions.

AIMS

We studied whether potent vasodilators hydrogen sulfide (H2S) and carbon monoxide (CO) can protect against alendronate-induced gastric lesions in rats exposed to mild stress.

METHODS

Three 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.

RESULTS

Alendronate 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.

CONCLUSION

Both 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.

Authors+Show Affiliations

Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Cracow, Poland.Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Cracow, Poland.Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Cracow, Poland.Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Cracow, Poland. Division of Molecular Biology and Clinical Genetics, Department of Medicine, Jagiellonian University Medical College, 8 Skawinska Street, 31-066, Cracow, Poland.Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Cracow, Poland.Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Cracow, Poland.Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Cracow, Poland. mpbrzozo@cyf-kr.edu.pl.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27541924

Citation

Magierowski, Marcin, et al. "Hydrogen Sulfide and Carbon Monoxide Protect Gastric Mucosa Compromised By Mild Stress Against Alendronate Injury." Digestive Diseases and Sciences, vol. 61, no. 11, 2016, pp. 3176-3189.
Magierowski M, Magierowska K, Szmyd J, et al. Hydrogen Sulfide and Carbon Monoxide Protect Gastric Mucosa Compromised by Mild Stress Against Alendronate Injury. Dig Dis Sci. 2016;61(11):3176-3189.
Magierowski, M., Magierowska, K., Szmyd, J., Surmiak, M., Sliwowski, Z., Kwiecien, S., & Brzozowski, T. (2016). Hydrogen Sulfide and Carbon Monoxide Protect Gastric Mucosa Compromised by Mild Stress Against Alendronate Injury. Digestive Diseases and Sciences, 61(11), 3176-3189.
Magierowski M, et al. Hydrogen Sulfide and Carbon Monoxide Protect Gastric Mucosa Compromised By Mild Stress Against Alendronate Injury. Dig Dis Sci. 2016;61(11):3176-3189. PubMed PMID: 27541924.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydrogen Sulfide and Carbon Monoxide Protect Gastric Mucosa Compromised by Mild Stress Against Alendronate Injury. AU - Magierowski,Marcin, AU - Magierowska,Katarzyna, AU - Szmyd,Jakub, AU - Surmiak,Marcin, AU - Sliwowski,Zbigniew, AU - Kwiecien,Slawomir, AU - Brzozowski,Tomasz, Y1 - 2016/08/19/ PY - 2015/12/28/received PY - 2016/08/10/accepted PY - 2016/10/19/pubmed PY - 2017/7/8/medline PY - 2016/8/20/entrez KW - Alendronate KW - Carbon monoxide KW - Gastric blood flow KW - Gastroprotection KW - Hydrogen sulfide KW - Hypoxia-inducible factor-1α SP - 3176 EP - 3189 JF - Digestive diseases and sciences JO - Dig Dis Sci VL - 61 IS - 11 N2 - BACKGROUND: Alendronate is an inhibitor of osteoclast-mediated bone resorption, but its clinical utility is limited due to gastrointestinal complications including bleeding erosions. AIMS: We studied whether potent vasodilators hydrogen sulfide (H2S) and carbon monoxide (CO) can protect against alendronate-induced gastric lesions in rats exposed to mild stress. METHODS: Three 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. RESULTS: Alendronate 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. CONCLUSION: Both 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. SN - 1573-2568 UR - https://www.unboundmedicine.com/medline/citation/27541924/Hydrogen_Sulfide_and_Carbon_Monoxide_Protect_Gastric_Mucosa_Compromised_by_Mild_Stress_Against_Alendronate_Injury_ L2 - https://doi.org/10.1007/s10620-016-4280-5 DB - PRIME DP - Unbound Medicine ER -