Protective effects of several drugs on gastric hemorrhagic ulcer in diabetic rats

• Main Authors: Chia-hui Lin, 林佳慧
• Other Authors: Chen-road Hung
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/89658289409244037783

碩士 === 國立成功大學 === 藥理學研究所 === 95 === Patients with diabetes mellitus may suffer from gastrointestinal disturbances, such as dysphagia, abdominal pain, nausea, vomiting, diarrhea and fecal incontinence. The integrity of gastric mucosa is greatly affected by offensive factors, such as increased gastric acid-back diffusion and free radicals generation as well as by decreased defensive substances, including glutathione and mucus production. Gastric mucosa of diabetic rats is highly vulnerable to injury, but little is known about the influence of diabetic conditions on the gastric hemorrhagic ulcers. Therefore, we investigated the pathophysiological mechanisms and several drug protective effects on hemorrhagic ulcer in diabetic rats. The aim is to study hemorrhagic ulcer induced by diabetes mellitus and protective effects of lysozyme, melatonin and garlic oil ,and compared them with traditional drugs famotidine, sucralfate and lansoprazole in diabetic rats. Intravenous streptozotocin (65mg/kg) was used to induced DM in rats. DM caused aggravation of various gastric offensive and defensive parameters in DM rat stomachs irrigated for 3hs with gastric juice. Aggravation of gastric parameters that associated with gastric oxidative stress such as acid back diffusion, hemoglobin content, and lipid peroxide, as well as decreased concentration of defensive substances, including glutathione and mucus content were observed in these DM rats. An increased gastric hemorrhagic ulcer also achieved in DM rats. These ulcerogenic parameters were doses-dependant effectively inhibited by daily administrated lansoprazole, fomatidine, sucralfate, melatonin, lysozyme and garlic oil in those DM rats. A complex system of interacting mediators exists in the gastric mucosa to strengthen its resistance against injury. In this system prostaglandins play an important role. Initially the concept was prostaglandins involved in pathophysiological reactions such as inflammation. Inflammatory cytokines (TNF-alpha, IL-1beta and i-NOS) significantly elevated in gastric mucosa of DM rats. Oral administrated anti-inflammatory drugs(TNF-α inhibitor – Pentoxifylline 20mg/kg; i-NOS inhibitor – Aminoguanidin 20mg/kg; COX inhibitor – Indomethacin 2.5mg/kg and COX-2 inhibitor - celicoxib;5mg/kg)to investigate the pathophysiological mechanisms on hemorrhagic ulcer in diabetic rats. These ulcerogenic parameters were effectively inhibited by daily administrated pentoxifylline and aminoguanidin decreased gastric hemorrhagic ulcer in DM rats. COX inhibitor and a selective COX-2 inhibitor when given added to DM rats the severe gastric damage develops. With the views of mechanisms of COX enzyme was discussed in the present. In conclusion, Indomethacin and celicoxib could produce deeper and more extensive mucosal hemorrhagic ulcer in DM rats than normal rats that is associated with oxidative stress, decreased mucus and inflammation. Exogenous insulin leading to hyperinsulinemia could decreased ulcer produced in DM rats.