Dalia H El-Kashef1, Ahmed A Shaaban2, Dina S El-Agamy3. 1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. 2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; Faculty of Pharmacy, Aqaba University of Technology, Aqaba, Jordan. 3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia. Electronic address: dagamiabdalla@taibahu.edu.sa.
Abstract
BACKGROUND: Pirfenidone (PFD) is an orally active antifibrotic agent that has anti-inflammatory activity in diverse animal models. Its effect against acute pancreatitis (AP) has not been elucidated. Hence, the present investigation was carried out to assess the potential protective role of PFD against l-arginine-induced AP in mice. METHODS: AP was induced in adult male Swiss albino mice via intraperitoneal injections of l-arginine (4 g/kg, twice each 1 h apart). PFD (250 mg/kg, orally) was administered one day before and on the day of l-arginine challenge. Twenty-four hours after l-arginine injection, the severity of AP was evaluated using biochemical and histological analyses. Indices of oxidative stress, inflammation and apoptosis were evaluated using ELISA and immunohistochemistry (IHC). RESULTS: PFD suppressed the development of l-arginine-induced AP as revealed by the improvement of histopathological lesions of pancreatic specimen and the significant reduction of serum amylase and lipase levels. Notably, PFD reduced the lipid peroxidation and enhanced the antioxidants such as reduced glutathione (GSH) and superoxide dismutase (SOD) in pancreatic tissue. Importantly, PFD suppressed AP-associated elevation of inflammatory cytokines along with depression of nuclear factor kappa-B (NF-κB) immuno-expression in pancreatic tissue. Lastly, PFD efficiently ameliorated AP-induced elevation of the pro-apoptotic protein (Bax) and increased AP-induced reduction of the anti-apoptotic protein (Bcl2). CONCLUSIONS: PFD protected against l-arginine-induced AP in mice through anti-oxidative, anti-inflammatory and anti-apoptotic properties.
BACKGROUND:Pirfenidone (PFD) is an orally active antifibrotic agent that has anti-inflammatory activity in diverse animal models. Its effect against acute pancreatitis (AP) has not been elucidated. Hence, the present investigation was carried out to assess the potential protective role of PFD against l-arginine-induced AP in mice. METHODS: AP was induced in adult male Swiss albino mice via intraperitoneal injections of l-arginine (4 g/kg, twice each 1 h apart). PFD (250 mg/kg, orally) was administered one day before and on the day of l-arginine challenge. Twenty-four hours after l-arginine injection, the severity of AP was evaluated using biochemical and histological analyses. Indices of oxidative stress, inflammation and apoptosis were evaluated using ELISA and immunohistochemistry (IHC). RESULTS:PFD suppressed the development of l-arginine-induced AP as revealed by the improvement of histopathological lesions of pancreatic specimen and the significant reduction of serum amylase and lipase levels. Notably, PFD reduced the lipid peroxidation and enhanced the antioxidants such as reduced glutathione (GSH) and superoxide dismutase (SOD) in pancreatic tissue. Importantly, PFD suppressed AP-associated elevation of inflammatory cytokines along with depression of nuclear factor kappa-B (NF-κB) immuno-expression in pancreatic tissue. Lastly, PFD efficiently ameliorated AP-induced elevation of the pro-apoptotic protein (Bax) and increased AP-induced reduction of the anti-apoptotic protein (Bcl2). CONCLUSIONS:PFD protected against l-arginine-induced AP in mice through anti-oxidative, anti-inflammatory and anti-apoptotic properties.