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, 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.

Prevalence and Clinical Characterization of Gastric Helicobacter Species Infection of Dogs and Cats in Korea

This study was carried out to evaluate the prevalence and clinical characterizations of gastric Helicobacter spp. infection of dogs and cats in Korea. The prevalence of Helicobacter spp. infection of dogs and cats determined by urease test was 78.4% and 64%, respectively, although Helicobacter genus-specific PCR assay showed that it was 82.3% and 84%. Urease mapping results based on urease test showed that total positive rate of tested tissues from clinically abnormal dogs was significantly higher than that from clinically normal dogs (p=0.0018; Odds ratio = 6.118; 95% Confidence Interval = 1.96~19.103). These findings were consistent with the results of Helicobacter genus-specific PCR assay which showed that positive rate of the fundus (100%) and the antrum (100%) of clinically abnormal dogs was significantly higher than that of same gastric regions of clinically normal dogs (77.5 and 67.5% respectively). In comparison of gastric regions between clinically normal dogs and abnormal dogs, positive rate of urease test for the fundus (100%) and body (90.9%) in clinically abnormal dogs was significantly higher than that of abnormal dogs (72.5% and 57.5% respectively; p<0.05). The results of urease mapping in dogs and cats also indicated that Helicobacter colonization in the fundus was more dense compared with the density in the body and antrum. In Helicobacter species-specific PCR assay for dogs, 32 of 42 fundic tissues (76.2%) were positive for H. heilmannii and two (4.8%) were positive for H. felis. In cats, 18 of 21 fundic tissues (85.7%) were positive for H. heilmannii and 2 (9.5%) were positive for H. felis. Gastritis scores of fundic tissues from clinically abnormal infected dogs were similar to that from noninfected dogs and evidence of upregulation of IL-1beta, IL-8, and TNF-alpha mRNA was not detected in gastric fundic tissues from clinically abnormal infected dogs. This study suggested that Helicobacter spp. infection in domestic dogs including private owned pet dogs and cats is highly prevalent usually with no clinical sign but high density of colonization can be related to gastrointestinal signs