Sulfasalazine inhibits inflammation and fibrogenesis in pancreas via NF-κB signaling pathway in rats with oxidative stress-induced pancreatic injury.
BACKGROUND
Pathogenesis and effective therapeutics of chronic pancreatic inflammation and fibrosis remain uncertain.


OBJECTIVE
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.


CONCLUSIONS
SF inhibits pancreatic inflammation and fibrogenesis via NF-κB signaling pathway.
Department of Gastroenterology, Shandong Qianfoshan Hospital, Shandong University, Ji'nan, Shandong Province, People's Republic of China.
Ya-Ru
YR
Wang
Shandong University School of Medicine, Qilu Hospital, Shandong University, Ji'nan, Shandong Province, People's Republic of China.
Fei-Long
FL
Tian
Department of Gastroenterology, Shandong Qianfoshan Hospital, Shandong University, Ji'nan, Shandong Province, People's Republic of China.
Ming-Xian
MX
Yan
Department of Gastroenterology, Shandong Qianfoshan Hospital, Shandong University, Ji'nan, Shandong Province, People's Republic of China.
Jin-Hua
JH
Fan
Department of Gastroenterology, Shandong Qianfoshan Hospital, Shandong University, Ji'nan, Shandong Province, People's Republic of China.
Li-Yun
LY
Wang
Department of Gastroenterology, Shandong Qianfoshan Hospital, Shandong University, Ji'nan, Shandong Province, People's Republic of China.
Rong-Guang
RG
Kuang
Department of Gastroenterology, Qilu Hospital, Shandong University, Ji'nan, Shandong Province, People's Republic of China.
Yan-Qing
YQ
Li
D000818:Animals; D005355:Fibrosis / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D012460:Sulfasalazine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*
D016328:NF-kappa B; D012460:Sulfasalazine
NF-κB; fibrogenesis; inflammation; pancreatic injury; sulfasalazine