Allopurinol in rat chronic pancreatitis: Effects on pancreatic stellate cell activation
Pancreas, cilt.35, sa.4, ss.366-371, 2007 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 35 Sayı: 4
- Basım Tarihi: 2007
- Doi Numarası: 10.1097/mpa.0b013e31806dbaaa
- Dergi Adı: Pancreas
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.366-371
- Anahtar Kelimeler: Allopurinol, Alpha smooth muscle actin, Chronic pancreatitis, Oxidative stress, Pancreatic stellate cells, Xanthine oxidase
- Trakya Üniversitesi Adresli: Hayır
Özet
OBJECTIVES: Activation of pancreatic stellate cells (PSCs) is a key event in pancreatic fibrosis. Xanthine oxidase-derived free radicals are involved in the mechanism of chronic pancreatitis (CP). We here searched the in vivo effects of allopurinol on PSC activation and its relation to tissue oxidative stress and histological findings in rat CP. METHODS: Rat CP was induced with intraductal trinitrobenzene sulfonic acid in groups 1 (n = 16) and 2 (n = 10). Group 3 (n = 10) received intraductal saline. Four weeks after induction, group 1 received allopurinol (200 mg/kg, SC), and groups 2 and 3 received saline. After 4 weeks, oxidative stress parameters, histological evaluation, and immunostaining for α-smooth muscle actin (+) PSCs were performed in the pancreata. RESULTS: Oxidative stress parameters improved significantly in group 1 compared with groups 2 and 3. Collagen deposition and lobular/sublobular atrophy were significantly lower in group 1 than in group 2. α-smooth muscle actin (+) PSCs counts in group 1 were significantly lower than in group 2, and were in correlation with the degree of fibrosis and atrophy. CONCLUSIONS: Allopurinol inhibits PSC activation in vivo. Pancreatic fibrosis can be prevented, at least in part, by antioxidant treatment through xanthine oxidase metabolism. Long-term use of allopurinol and its analogs may be considered in clinical trials with CP. © 2007 Lippincott Williams & Wilkins, Inc.