Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0149521 (chronic pancreatitis)
 7,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently demonstrated that both lisinopril and candesartan, an angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor blocker, respectively, attenuate pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori (WBN/Kob) rats. The purpose of the present study was to assess whether combination therapy with low doses of both, ineffective when given alone, might synergistically exert protective effects. Lisinopril, candesartan, or a combination of both in drinking water was administered to 10-week-old male WBN/Kob rats for 10 weeks. Parameters of inflammation and fibrosis, positive immunostaining for alpha-smooth muscle actin, and gene expression of cytokine and growth factors were assessed, as well as circulating renin-angiotensin system components. Dose-dependent effects of combination therapy were also investigated. Only combination therapy attenuated gross alterations in the pancreas, as quantitatively confirmed by increases in pancreatic weights and decreases in myeloperoxidase activity, hydroxyproline content, histologic scores, relative fibrosis area, and relative area of alpha-smooth muscle actin-positive cells. Combination therapy suppressed up-regulation of tumor necrosis factor-alpha, platelet-derived growth factor-receptor beta, and transforming growth factor-beta1 mRNA in the pancreas. Dose dependence of combination therapy was recognized with reference to improvement in these parameters. The conclusions are that combination therapy synergistically alleviated pancreatic inflammation and fibrosis in male WBN/Kob rats. This effect may be related to suppression of tumor necrosis factor-alpha, platelet-derived growth factor-receptor beta, and transforming growth factor-beta1 mRNA. Compared with the either therapy alone, combination therapy with an angiotensin-converting enzyme inhibitor and an angiotensin II type 1 receptor blocker may be more beneficial for treating chronic pancreatitis.
 ...
PMID:Combination therapy with an angiotensin-converting enzyme inhibitor and an angiotensin II receptor blocker synergistically suppresses chronic pancreatitis in rats. 1560 84

Lisinopril (angiotensin-converting enzyme inhibitor) attenuates fibrotic changes in pancreas after distal pancreatectomy in rats with experimental alcohol induced chronic pancreatitis. Lisinopril was administered after distal pancreatectomy in rats with experimental alcohol induced chronic pancreatitis. The animals were treated with lisinopril at the dose of 10 mg/kg body weight per day for 21 days after operation. To estimate the efficacy of the treatment on activity and number of pancreatic stellate cells the immunohistochemical investigation was made with alpha-smooth muscle actin (alpha-SMA), desmin, vimentin, glial fibrillary acidic protein (GFAP), matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-2 (TIMP-2) using. The treatment of rats after operation with lisinopril inhibite activity of pancreatic stellate cells and characterized by significant decrease of the alpha-SMA, desmin, GFAP, vimentin and TIMP-2 expression. The ratio of MMP-1/TIMP-2 was greater in the group with treatment then in the control group. This therapy had a trend to alleviate the fibrotic changes in pancreas.
 ...
PMID:[Inhibition of pancreatic stellate cell activation by lisinopril for prevention fibrogenesis in experimental chronic alcoholic pancreatitis]. 2303 81

Complex application of lisinopril (inhibitor of angiotensin-converting enzyme) and lovastatin (inhibitor of HMG-CoA reductase) inhibits pancreatic fibrosis in the rats, having alcoholic chronic pancreatitis after distal pancreatic resection (DPR). Lisinopril and lovastatin were injected to the rats after DPR in dose 10 mg/kg during 3 weeks. Immunohistochemical markets, such as alpha-smooth-muscle actin (alpha-SMA), desmin, glial fibrillary acidic protein (GFAP), vimentin, and expression of matrix metalloproteinase-1 (MMP-1) as well as inhibitor of matrix metalloproteinase-2 (TIMP-2) were detected for estimation of therapeutic impact on activity and quantity of stellate pancreatic cells. Under the influence of lisinopril and lovastatin there were observed lowering in the stellate pancreatic cells activity and in expression of SMA, desmin, GFAP, vimentin and TIMP-2, the MMP-1 and TIMP-2 ratio have had increased significantly and severity of fibrotic pancreatic affection had reduced trustworthy in comparison w such, occurring in a control group.
 ...
PMID:[Inhibition of the stellate cells using lisinopril and lovastatin for prophylaxis of pancreatic stump fibrosis after performance of distal resection in a model of chronic alcoholic pancreatitis]. 2370 87