title: Severity of pancreatitis‑associated intestinal mucosal barrier injury is reduced following treatment with the NADPH oxidase inhibitor apocynin.
abstract: Recent studies demonstrated that apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) inhibitor, significantly decreased acute pancreatitis‑associated inflammatory and oxidative stress parameters. In addition, apocynin was able to reduce ischemic reperfusion injury‑associated damage; however, the exact effects of apocynin on acute pancreatitis‑associated intestinal mucosal injury have yet to be fully clarified. The present study aimed to investigate the protective effects of apocynin on intestinal mucosal injury in a rat model of severe acute pancreatitis (SAP). A total of 60 male Sprague Dawley rats were randomly divided into four groups (n=15/group): Sham operation group (SO), SAP group, apocynin treatment (APO) group and drug control (APO‑CON) group. SAP was induced by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. Apocynin was administered 30 min prior to SAP induction in the APO group. All rats were sacrificed 12 h after SAP induction. Intestinal integrity was assessed by measuring diamine oxidase (DAO) levels. Morphological alterations to intestinal tissue were determined under light and transmission electron microscopy. NOX2, p38 mitogen‑activated protein kinases (MAPK) and nuclear factor (NF)‑κB expression levels were detected in the intestine by immunohistochemical staining. Oxidative stress was detected by measuring intestinal malondialdehyde (MDA) and superoxide dismutase content. In addition, blood inflammatory cytokines, and amylase (AMY) and lipase (LIP) levels were evaluated. The results demonstrated that apocynin attenuated the following: i) Serum AMY, LIP and DAO levels; ii) pancreatic and intestinal pathological injury; iii) intestinal MDA content; iv) intestinal ultrastructural alterations; v) serum interleukin (IL)‑1β, IL‑6 and tumor necrosis factor (TNF)‑α levels; and vi) NOX2, p38 MAPK and NF‑κB expression in intestinal tissues. These results suggested that apocynin may attenuate intestinal barrier dysfunction in sodium taurocholate‑induced SAP, presumably via its role in the prevention of reactive oxygen species generation and inhibition of p38 MAPK and NF‑κB pathway activation. These findings provide novel insight suggesting that pharmacological inhibition of NOX by apocynin may be considered a novel therapeutic method for the treatment of intestinal injury in SAP.
authors: Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Wenhong
authors: W
authors: Deng
authors: Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Ablikim
authors: A
authors: Abliz
authors: Department of General Surgery, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China.
authors: Sheng
authors: S
authors: Xu
authors: Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Rongze
authors: R
authors: Sun
authors: Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Wenyi
authors: W
authors: Guo
authors: Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Qiao
authors: Q
authors: Shi
authors: Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Jia
authors: J
authors: Yu
authors: Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Weixing
authors: W
authors: Wang
mesh_terms: D000098:Acetophenones / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D016207:Cytokines / Q000032:analysis; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016328:NF-kappa B / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis
chemical_list: D000098:Acetophenones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D016207:Cytokines; D004791:Enzyme Inhibitors; D016328:NF-kappa B; C056165:acetovanillone; D019255:NADPH Oxidases; D048051:p38 Mitogen-Activated Protein Kinases