The hydrogen sulfide donor,Lawesson's reagent,prevents
alendronate-induced gastric damage in rats |
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Authors: | LAD Nicolau RO Silva SRB Damasceno NS Carvalho NRD Costa KS Arag?o ALR Barbosa PMG Soares MHLP Souza JVR Medeiros |
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Institution: | 1.Núcleo de Pesquisa em Produtos Naturais, Departamento de Farmacologia, Universidade Federal do Piauí, Teresina, PI, Brasil;2.Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI, Brasil;3.Laboratório de Farmacologia da Inflamação e do Câncer, Departamento de Farmacologia, Universidade Federal do Ceará, Fortaleza, CE, Brasil |
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Abstract: | Our objective was to investigate the protective effect of Lawesson''s reagent, an
H2S donor, against alendronate (ALD)-induced gastric damage in rats.
Rats were pretreated with saline or Lawesson''s reagent (3, 9, or 27 µmol/kg,
po) once daily for 4 days. After 30 min, gastric damage was
induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the
animals were killed 4 h after ALD administration. Gastric lesions were measured using
a computer planimetry program, and gastric corpus pieces were assayed for
malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines tumor necrosis
factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were
pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5
mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27
µmol/kg Lawesson''s reagent was administered. After 30 min, 30 mg/kg ALD was
administered. ALD caused gastric damage (63.35±9.8 mm2); increased levels
of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g,
respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels
(180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the
gastric mucosa. Pretreatment with Lawesson''s reagent (27 µmol/kg) attenuated
ALD-mediated gastric damage (15.77±5.3 mm2); reduced TNF-α, IL-1β, and MDA
formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively);
lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric
tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect
of Lawesson''s reagent. However, glibenclamide plus diazoxide did not alter the
effects of Lawesson''s reagent. Our results suggest that Lawesson''s reagent plays a
protective role against ALD-induced gastric damage through mechanisms that depend at
least in part on activation of ATP-sensitive potassium (KATP)
channels. |
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Keywords: | Alendronate Lawesson''s reagent H2S donors Gastric damage |
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