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- Title
Inactivation of Kupffer Cells by Selenizing Astragalus Polysaccharides Prevents CCl-Induced Hepatocellular Necrosis in the Male Wistar Rat.
- Authors
Hamid, Mohammed; Liu, Dandan; Abdulrahim, Yassin; Khan, Alamzeb; Qian, Gang; Huang, Kehe
- Abstract
Selenizing astragalus polysaccharides-3 (sAPS) was prepared by nitric acid-sodium selenite method. The effects of sAPS on carbon tetrachloride (CCl) induced hepatocellular necrosis, and its underlying mechanisms were studied in male Wistar rats. Hepatic damage was induced by intraperitoneal injection of CCl twice a week, for 3 weeks. Meanwhile, the rats in addition to CCl were also exposed to sodium selenite (SS), astragalus polysaccharides (APS), SS + APS or sAPS, in parallel by oral gavage once a day for 3 weeks. At the end of 3 weeks, blood and liver tissue were taken. Serum was collected to test the levels of alanine aminotransferase, aspartate aminotransferase and antioxidant status parameters. Liver tissue was collected for histopathological examination and determination of messenger RNA (mRNA) expression levels of CD68, TNF-α, IL-1β and ATG7 followed by the measurements of CD68, IL-1β and LC3II by immunohistochemistry assay (IHC), or TNF-α by immunofluorescence assay (IFA). The results showed that sAPS effectively ameliorated CCl induced hepatocellular necrosis and inflammation and significantly decreased the levels of aspartate aminotransferase, alanine aminotransferase, malondialdehyde and the expression levels of Kupffer cells (KCs)-specific biomarker CD68 and proinflammatory cytokines produced by activated KCs such as IL-1β and TNF-α ( P < 0.01). While increasing the levels of total antioxidant capacity, glutathione, glutathione peroxidase and superoxide dismutase ( P < 0.05) and reduced the expression levels of a key regulator of autophagy in KCs ATG7 or LC3II ( P < 0.05). These findings indicate that sAPS could ameliorate CCl-induced hepatocellular necrosis by inactivation of Kupffer cells and its activity may be superior to the application of selenium, APS or combination of selenium with APS.
- Subjects
POLYSACCHARIDES; NITRIC acid; SODIUM selenite; CARBON tetrachloride; INTRAPERITONEAL injections; SERUM
- Publication
Biological Trace Element Research, 2017, Vol 179, Issue 2, p226
- ISSN
0163-4984
- Publication type
Article
- DOI
10.1007/s12011-017-0970-x