title: The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats.
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 mm(2)); 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 mm(2)); 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.
authors: Universidade Federal do Piauí, Núcleo de Pesquisa em Produtos Naturais, Departamento de Farmacologia, TeresinaPI, Brasil.
authors: L A D
authors: LA
authors: Nicolau
authors: R O
authors: RO
authors: Silva
authors: S R B
authors: SR
authors: Damasceno
authors: N S
authors: NS
authors: Carvalho
authors: N R D
authors: NR
authors: Costa
authors: K S
authors: KS
authors: Aragão
authors: A L R
authors: AL
authors: Barbosa
authors: P M G
authors: PM
authors: Soares
authors: M H L P
authors: MH
authors: Souza
authors: J V R
authors: JV
authors: Medeiros
mesh_terms: D019386:Alendronate / Q000037:antagonists & inhibitors*; D000704:Analysis of Variance; D000818:Animals; D003542:Cystathionine gamma-Lyase / Q000032:analysis; D003936:Diagnosis, Computer-Assisted; D003981:Diazoxide / Q000008:administration & dosage; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D005978:Glutathione / Q000032:analysis; D005905:Glyburide / Q000008:administration & dosage; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007202:Indicators and Reagents / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000032:analysis; D054086:KATP Channels / Q000494:pharmacology; D008315:Malondialdehyde / Q000032:analysis; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D009195:Peroxidase / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013272:Stomach Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D007202:Indicators and Reagents; D053583:Interleukin-1beta; D054086:KATP Channels; D009946:Organothiophosphorus Compounds; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; C029887:2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide; D009195:Peroxidase; D003542:Cystathionine gamma-Lyase; D005978:Glutathione; D003981:Diazoxide; D005905:Glyburide; D019386:Alendronate; D006862:Hydrogen Sulfide
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