The hydrogen sulfide donor,Lawesson's reagent,prevents alendronate-induced gastric damage in rats

Our objective was to investigate the protective effect of Lawesson''s reagent, anH₂S 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 wasinduced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, theanimals were killed 4 h after ALD administration. Gastric lesions were measured usinga computer planimetry program, and gastric corpus pieces were assayed formalondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosisfactor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups werepretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27µmol/kg Lawesson''s reagent was administered. After 30 min, 30 mg/kg ALD wasadministered. ALD caused gastric damage (63.35±9.8 mm²); increased levelsof 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 thegastric mucosa. Pretreatment with Lawesson''s reagent (27 µmol/kg) attenuatedALD-mediated gastric damage (15.77±5.3 mm²); reduced TNF-α, IL-1β, and MDAformation (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 gastrictissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effectof Lawesson''s reagent. However, glibenclamide plus diazoxide did not alter theeffects of Lawesson''s reagent. Our results suggest that Lawesson''s reagent plays aprotective role against ALD-induced gastric damage through mechanisms that depend atleast in part on activation of ATP-sensitive potassium (K_ATP)channels.