Original Article
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World J Gastroenterol. May 21, 2013; 19(19): 2894-2903
Published online May 21, 2013. doi: 10.3748/wjg.v19.i19.2894
Long-term aspirin pretreatment in the prevention of cerulein-induced acute pancreatitis in rats
Ibrahim Akyazi, Evren Eraslan, Ahmet Gülçubuk, Elif Ergül Ekiz, Zeynep L Çırakli, Damla Haktanir, Deniz Aktaran Bala, Mete Özkurt, Erdal Matur, Mukaddes Özcan
Ibrahim Akyazi, Evren Eraslan, Elif Ergül Ekiz, Deniz Aktaran Bala, Erdal Matur, Mukaddes Özcan, Department of Physiology, Veterinary Faculty, Istanbul University, 34320 Istanbul, Turkey
Ahmet Gülçubuk, Damla Haktanir, Department of Pathology, Veterinary Faculty, Istanbul University, 34320 Istanbul, Turkey
Zeynep L Çırakli, Department of Biochemistry, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, 34147 Istanbul, Turkey
Mete Özkurt, Department of Physiology, Faculty of Medicine, Eskişehir Osmangazi University, 26480 Eskisehir, Turkey
Author contributions: Akyazi I planned the study, conducted the project, and performed the cytokine, aspirin-triggered lipoxins and nuclear factor-κB analyses; Eraslan E helped to plan the project, and performed the NO and Catalase analyses; Gülçubuk A conducted the histopathological scoring; Ekiz EE performed the hemeoxygenase-1 and superoxide dismutase analyses; Çırakli ZL analyzed the biochemical parameters; Haktanir D performed the histopathological preparation of tissues and scoring; Bala DA and Özkurt M collected the samples; Matur E helped to plan the project and conducted the malondialdehyde analysis; Özcan M supervised the project.
Supported by The Istanbul University Department of Scientific Research Projects, Grant No. 3101
Correspondence to: Ibrahim Akyazi, DVM, PhD, Department of Physiology, Veterinary Faculty, Istanbul University, 34320 Istanbul, Turkey. iakyazi@istanbul.edu.tr
Telephone: +90-536-9690720 Fax: +90-212-4737218
Received: November 14, 2012
Revised: January 23, 2013
Accepted: February 5, 2013
Published online: May 21, 2013
Processing time: 186 Days and 16.5 Hours
Abstract

AIM: To investigate the effects of long term pretreatment with low-, medium- and high-dose aspirin (acetylsalicylic acid, ASA) on a model of acute pancreatitis (AP) induced in rats.

METHODS: Forty male Wistar rats were used. Three experimental groups, each consisting of eight animals, received low- (5 mg/kg per day), medium- (150 mg/kg per day) and high-dose (350 mg/kg per day) ASA in supplemented pellet chow for 100 d. Eight animals, serving as the AP-control group, and another eight, serving as reference value (RV) group, were fed with standard pellet chow for the same period. After pretreatment, AP was induced in the experimental animals by intraperitoneal administration of cerulein (2 × 50 μg/kg), while the RV group received saline in the same way. Twelve hours after the second injection, the animals were sacrificed. Pancreatic tissue and plasma samples were collected. One part of the collected pancreatic tissues was used for histopathological evaluation, and the remaining portion was homogenized. Cytokine levels [tumor necrosis factor, interleukin (IL)-1β, IL-6], hemogram parameters, biochemical parameters (amylase and lipase), nuclear factor-κB, aspirin triggered lipoxins and parameters related to the antioxidant system (malondialdehyde, nitric oxide, hemeoxygenase-1, catalase and superoxide dismutase) were measured.

RESULTS: Cerulein administration induced mild pancreatitis, characterized by interstitial edema (total histopathological score of 5.88 ± 0.44 vs 0.25 ± 0.16, P < 0.001). Subsequent pancreatic tissue damage resulted in an increase in amylase (2829.71 ± 772.48 vs 984.57 ± 49.22 U/L, P = 0.001) and lipase (110.14 ± 75.84 U/L vs 4.71 ± 0.78 U/L, P < 0.001) in plasma, and leucocytes (6.89 ± 0.48 vs 4.36 ± 0.23, P = 0.001) in peripheral blood. Cytokines, IL-1β (18.81 ± 2.55 pg/μg vs 6.65 ± 0.24 pg/μg, P = 0.002) and IL-6 (14.62 ± 1.98 pg/μg vs 9.09 ± 1.36 pg/μg, P = 0.04) in pancreatic tissue also increased. Aspirin pretreatment reduced the increase in the aforementioned parameters to a certain degree and partially improved the histopathological alterations caused by cerulein. No evidence of side effects related to chronic ASA administration (e.g., inflammation or bleeding) was observed in the gastrointestinal tract in macroscopic and histopathological examination.

CONCLUSION: Long term ASA pretreatment could prevent and/or ameliorate certain hematological, serological and histological alterations caused by cerulein-induced AP.

Keywords: Aspirin; Acute pancreatitis; Cerulein; Antioxidant; Cytokines

Core tip: Acute pancreatitis (AP) is an inflammatory and potentially life-threatening disease. An estimated 80000 cases of AP occur each year in the United States. There is no specific cure for AP; therefore, research interest has focused on prevention strategies. In the present study, the effects of a long-term pretreatment with different doses of aspirin, the oldest and most widely used non-steroidal anti-inflammatory drug, were investigated on a AP model in rats. Our results indicated that aspirin pretreatment dose-dependently prevents or ameliorates some hematological, serological and histological alterations caused by cerulein-induced AP.