LASSBio-596 protects gastric mucosa against the development of ethanol-induced gastric lesions in mice.

LASSBio-596 (2-[4-(1,4-thiazinan-4-ylsulfonyl) phenylcarbamoyl] benzoic acid) is a molecular hybrid of anti-tumor necrosis factor α (TNF-α) and phosphodiesterase 5 inhibitors, and its anti-inflammatory effects have been demonstrated in experimental models of inflammation. The aim of this study was to evaluate the gastroprotective effect of LASSBio-596 in an ethanol-induced acute gastritis model. Before induction of gastric damage, mice were pretreated with LASSBio-596 (20 mg per os (p.o.), Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME; 3 mg/kg, intraperitoneally [i.p.]) or with 1400W (10 mg/kg, i.p.) given alone or in their combinations. Thirty minutes later, gastric damage was induced by intragastric instillation of 50% ethanol (0.5 ml/25 g, by gavage). After 1 h, gastric damage (hemorrhagic or ulcerative lesions) was measured by planimetry. Samples of the stomach were also taken for histopathological assessment and for assays of tissue myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), and inflammatory cytokines. Ethanol administration induced the development of gastric lesions in mice. LASSBio-596 reduced gastric damage, epithelial cell loss and hemorrhage, and restored the antioxidant defense system by decreasing the levels of MDA and the consumption of GSH in gastric mucosa. LASSBio-596 also decreased gastric TNF-α and interleukin-1ß (IL-1ß) protein levels, MPO enzymatic activity, and hemoglobin levels. Treatment with the nitric oxide synthase inhibitors L-NAME and 1400W reversed the effects of LASSBio-596 on ethanol-induced gastric lesions. LASSBio-596 did not alter mucus content and pH of gastric secretions. In summary, LASSBio-596 exerts protective effects against ethanol-induced gastric injury. The gastroprotective effects of LASSBio seem to be NO-dependent.

Ximenia americana heteropolysaccharides ameliorate inflammation and visceral hypernociception in murine caerulein-induced acute pancreatitis: Involvement of CB2 receptors.

BACKGROUND: This study aimed to investigate and characterize the anti-inflammatory and anti-hypernociceptive effects of the total polysaccharides of X. americana (TPL-Xa) bark in a mouse model of acute pancreatitis-induced by caerulein and the potential involvement of cannabinoid receptors. METHODS: TPL-Xa was characterized by1H and 13C NMR spectroscopy. Animals received TPL-Xa (10 mg/kg, i.v.) 30 min before and after caerulein (50 µg/kg, 10×, i.p.) administration. To evaluate the involvement of cannabinoid receptors, AM281 (3 mg/kg, s.c.) and AM630 (1 mg/kg, s.c.) were administered 30 min before TPL-Xa. Plasma levels of amylase and lipase, pancreatic myeloperoxidase (MPO), histology, visceral hypernociception and motor coordination were evaluated 11 and 24 h after acute pancreatitis (AP) induction. RESULTS: TPL-Xa, containing a heteropolysaccharide composed of glucose, galactose, arabinose, rhamnose, fucose and galacturonic acid, reduced amylase and lipase levels, MPO activity, acinar cell necrosis, edema and neutrophil infiltration. TPL-Xa increased the threshold of visceral hypernociception, an effect reversed by AM630, an antagonist of cannabinoid receptor type 2 (CB2). In addition, TPL-Xa did not alter the animals' motor coordination. CONCLUSIONS: TPL-Xa contains heteropolysaccharides that inhibit inflammation and hypernociception in the experimental model of caerulein-induced AP, by a mechanism involving type CB2 receptors.