Sulfasalazine inhibits inflammation and fibrogenesis in pancreas via NF-&kappa;B signaling pathway in rats with oxidative stress-induced pancreatic injury
Authors: Li-Yun Wang
Ya-Ru Wang
Rong-Guang Kuang
Jin-Hua Fan
Ming-Xian Yan
Fei-Long Tian
Yan-Qing Li
Journal: Drug Design Development and Therapy (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: NF-κB; fibrogenesis; inflammation; pancreatic injury; sulfasalazine.
Affiliations: Department of Gastroenterology, Shandong Qianfoshan Hospital, Shandong University, Ji'nan, Shandong Province, People's Republic of China., Shandong University School of Medicine, Qilu Hospital, Shandong University, Ji'nan, Shandong Province, People's Republic of China., Department of Gastroenterology, Qilu Hospital, Shandong University, Ji'nan, Shandong Province, People's Republic of China.

Abstract:  Background: Pathogenesis and effective therapeutics of chronic pancreatic inflammation and fibrosis remain uncertain. Purpose: To investigate the effects of sulfasalazine (SF) on pancreatic inflammation and fibrogenesis. Methods: Chronic pancreatic injury in rats was induced by diethyldithiocarbamate (DDC) and interfered by SF through intraperitoneal injection. The rats were divided into five groups: group N, normal control group, rats were treated with dilated water only; group DS1, rats received SF (10 mg/kg) 2 hours before DDC treatment; group DS2, rats were treated with DDC and then SF (100 mg/kg, twice a week); group DS3, rats were treated with DDC, then SF (100 mg/kg, thrice a week); and group DDC, rats were treated with DDC only. Pancreatic inflammation and fibrosis were determined by hematoxylin and eosin staining and Sirius red staining. The genes and proteins related to NF-κB pathway and fibrogenesis including NF-κB/p65, TNF-α, ICAM-1, α-SMA, and Con 1 were detected by immunohistochemical staining, reverse transcription polymerase chain reaction, and Western blotting. Results: Rats in the DDC and DS1 groups showed the highest histological scores after DDC treatment, but the scores of DS2 and DS3 groups decreased significantly when compared with the DDC group. Sirius red staining showed collagen formation clearly in DDC and DS1 rats rather than in DS2 and DS3 rats. NF-κB/p65, ICAM-1, and α-SMA were strongly expressed in DDC and DS1 rats, while DS2 and DS3 rats showed mild to moderate expression by immunohistochemistry. Reverse transcription polymerase chain reaction showed increased levels of NF-κB/p65, ICAM-1, TNF-α, α-SMA, and Con 1 mRNA in DDC and DS1 rats in comparison to normal controls. The mRNA levels of these molecules in DS2 and DS3 rats were significantly lower than those in DS1 and DDC rats. Western blotting demonstrated that the NF-κB/p65, ICAM-1, and α-SMA expressions in pancreatic tissues of the rats of the DDC group were more clear than those of the normal control, DS2, and DS3 rats. Conclusion: SF inhibits pancreatic inflammation and fibrogenesis via NF-κB signaling pathway. 

Retracted: No

PubPeer comments:
 Two images in Figure 1 appear to overlap. TAM. *** ![file] , 
 Dear Dr. TAM (Actinopolyspora Biskrensis), Thanks for your comments. I will check our data as soon as possible to determine whether there was a wrong figure. Thank you very much. Regards, Yan, Ming-Xian , 
 #2 Thank you for your prompt reply. As the samples are labeled as coming from different groups, one would not expect them to overlap. Since the histological scoring is dependent upon the tissues measured, it is concerning that the images were organized in a way that would permit an error of this type to occur. Is the original data still available and complete? , 
 yes we should have the data. I transferred them to a CD disk, should also in an other retired laptop. I need time to confirm. , 
 Dear Actinopolyspora Biskrensis, We checked our data, and we are sure now that you are right, we made an error. When we made figure 1, we chose b and c from the same group of candidate representative images. We are revising fig 1, and then contacting the journal editor to correct the error. Thank you for your work. Dr. Ming-Xian Yan , 
 Corrigendum published 16 June 2021 The authors have advised Figure 1A on page 1746 is incorrect. The authors inadvertently chose b and c from the same group of candidate representative images during figure assembly. The correct Figure 1 is shown below. The authors apologize for this error and advise it does not affect the results of the paper. ![file] , 
 In addition to the previous concerns, many of the images in this paper have small regions that appear to be repeated. Could the authors please examine the original data to see if this issue exists there? Figure 3C is shown as an example. *** ![file] , 
 Two images in Figure 2 appear to overlap, but seem to be described as representing two different treatment groups. I also marked a couple of the images where the small duplicated regions also seem to appear. *** ![file] , 
 ![file] ![file] ![file] ![file] ![file] Above are original images for Fig3C , 
 ![file] This is an original image for Fig2A , 
 It is hard for me to find repeated samll regions in these original images. I don t konw why they look that when published. But we misused images in Fig2A, as Fig2A b e shows. We appoligize for that. And thanks very much . , 
 Based on their location it may be that the small duplicated regions in the published Fig. 2a and Fig. 3a are related to brushing away a misplaced image label. Though I would not know why someone with access to the originals would do that. Fig. 2b and e obviously need a correction. I hope the authors are certain the other images are correct. [ Click to animate. Original versus published Fig. 2a ] ![file] [ Click to animate. Original versus published Fig. 3a ] ![file] , 
 Retracted[18 August 2022] . ------------------- At the authors request, the Editor and Publisher of *Drug Design, Development and Therapy* wish to retract the published article. Previous concerns had been raised to the authors regarding the alleged duplication of images in Figures 1A-b and 1A-c and a corrigendum had been published. More recently, concerns have also been raised to the authors regarding the alleged duplication of images between Figure 2A-b and 2A-e. In addition, there were also concerns raised regarding the duplication of certain features between several images from Figures 2 and 3. The journal wishes to recognize that these particular concerns were introduced during the publication process and were not introduced by the authors. However, in relation to the duplication of images between Figure 2A-b and 2A-e, the authors have acknowledged this. The authors were able to provide original data to the journal, but it was unable to support the integrity of the research and the authors requested to retract the article and the Editor agreed with this. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,