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| Id: |
lil-684527
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| Autor: |
Brazilian Journal of Medical and Biological Research; Nicolau, L.A.D.; Silva, R.O.; Damasceno, S.R.B.; Carvalho, N.S.; Costa, N.R.D.; Aragao, K.S.; Barbosa, A.L.R.; Soares, P.M.G.; Souza, M.H.L.P.; Medeiros, J.V.R.. |
| Título: |
The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats |
| Fonte: |
Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;46(8):708-714, ago. 2013. tab, graf.
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| Idioma: |
en.
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| Resumo: |
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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| Descritores: |
Alendronato/antagonistas & inibidores
Mucosa Gástrica/efeitos dos fármacos
Sulfeto de Hidrogênio/farmacologia
Indicadores e Reagentes/farmacologia
Compostos Organotiofosforados/farmacologia
Gastropatias/induzido quimicamente
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-Análise de Variância
Cistationina gama-Liase/análise
Diagnóstico por Computador
Diazóxido/administração & dosagem
Mucosa Gástrica/patologia
Glutationa/análise
Glibureto/administração & dosagem
Interleucina-1beta/análise
Canais KATP/farmacologia
Malondialdeído/análise
Peroxidase/análise
Peroxidase/metabolismo
Ratos Wistar
Gastropatias/enzimologia
Gastropatias/patologia
Fator de Necrose Tumoral alfa/análise
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| Limites: |
Animais
Feminino
Ratos
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| Tipo de Publ: |
Research Support, Non-U.S. Gov't
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| Responsável: |
BR1.1 - BIREME
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